1. health and fitness
2. disorders

Collegium Internationale
Neuro-Psychopharmacologicum
A Research and Education Conference
Major Psychoses
and Substance Abuse
Edinburgh International Conference Centre
(EICC), Edinburgh, Scotland
25 - 27 April 2009
Programme
and Abstract Book
Contents
Conference Planning & Executive Committee Welcome
Background
Registration
Conference Information
Preliminary Programme at a Glance
Speaker Abstracts and Biographies
Rafaelsen Young Investigators Travel Award
Poster Abstracts
Travel Information Delegate List Edinburgh City Centre Map/Key
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Conference Planning and Executive Committee
CINP Executive Committee 2008-2010
CINP President
Robert H. Belmaker, Israel
Past-President
Torgny H. Svensson, Sweden
President-Elect
Hans-Jürgen Möller, Germany
Vice Presidents
W. Wolfgang Fleischhacker, Austria
Anthony Phillips, Canada
Secretary
Shitij Kapur, UK
Treasurer
Lars Farde, Sweden
Executive Secretary
Gill Moore, UK
Local Organising Committee
W. Wolfgang Fleischhacker, Austria, Chairman
Robert H. Belmaker, Israel, Co-Chair
Torgny H. Svensson, Sweden, Co-Chair
Anissa Abi-Dargham, USA
Alan Green, USA
Eve Johnstone, UK
John Krystal, USA
Brian Leonard, Ireland
Robin Murray, UK
Georg Winterer, Germany
Local Professional Conference Organiser
Northern Networking Events Ltd
Glenfinnan Suite
Braeview House
9/11 Braeview Place
East Kilbride
G74 3XH
Scotland, UK
Tel: +44 (0) 1355 244930
Fax: +44 (0) 1355 249959
Email: [email protected]
Conference organiser’s web:
www.northernnetworking.co.uk
CINP Website: www.cinp.org
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Collegium Internationale Neuro-Psychopharmacologicum
WELCOME LETTER
Welcome
We would like to extend a warm welcome to all our participants at this first Thematic Meeting for the Collegium
Internationale Neuro-psychopharmacologicum (CINP) which is taking place in Edinburgh the capital city of
Scotland. CINP have focussed this meeting on Education and Research in the field of major psychoses and
substance abuse and I trust over the coming few days your objectives for attending this meeting are met.
We are honoured to have so many experts in the field of psychoses and substance abuse gathered together and
I very much hope you have the opportunity to discuss at first hand any questions you may have. This meeting
has been intentionally designed to be more focused with a smaller group to allow for one to one discussions.
It is also pleasing to see our young Rafaelsen Travel Award winners here in person to receive their prize and to
enjoy the few days of science. We had an overwhelming number of applications for this meeting and would
like to encourage those who were not successful to apply again for the Rafaelsen Travel Award which will be
available for our biennial Congress which takes place 6 – 10 June 2010 in Hong Kong.
CINP are always looking for new ways to develop the Association and would warmly welcome new members.
We are particularly keen to develop a section for younger members and would like to encourage all our poster
presenters to consider applying for membership.
Finally in addition to the days of top level science please make the most of being in this Northern European
Capital City, and visit some of the many historic sights which are just on the doorstep.
Prof Wolfgang Fleischhacker
Conference Chairman and CINP Vice President
Prof R H Belmaker Conference Co-Chairman and CINP President
Collegium Major
Internationale
Psychoses
Neuro-Psychopharmacologicum
and Substance Abuse
Prof. Torgny H. Svensson
Conference Co-Chairman
and CINP Past President
33
Contents
CONFERENCE
BACKGROUND
INFORMATION
CINP Thematic Meeting on Major
Psychoses & Substance Abuse
An innovative and exciting new format of CINP meeting
begins in 2009. This Thematic Meeting is international
in scope with an engaging mixture of education sessions
and scientific symposia. The meeting is focused on
a single theme, concentrating on specific topics and
incorporating educational and professional development
in addition to research sessions. The first such CINP
Thematic Meeting is being held at the Edinburgh
International Conference Centre (EICC), Edinburgh,
Scotland, UK from Saturday 25 to Monday 27 April
2009, one of the world’s leading capital cities with a
dramatic setting and vibrant culture.
The theme is “Major Psychoses & Substance Abuse”.
We are delighted to bring together many of the opinion
leaders in the challenging area of co-morbidity issues
relating to Major Psychoses and Substance Abuse. Our
Plenary Lecturers Prof. Robin Murray, Prof. Trevor Robbins
and Prof. Alan Green will set the scene for the meeting,
and you the delegate will have the opportunity to meet at
first hand the key research workers in the fields of Major
Psychoses and Substance Abuse.
EDINBURGH, SCOTLAND
The tantalising prospect of time away in one of Europe’s
most beautiful capitals is hard to resist. Everything you
could hope for from a city is on offer in Edinburgh, all
within easy reach of the EICC. There is an unprecedented
range of cultural choices, exceptional art galleries,
museums, restaurants and pubs. Edinburgh is also home
to Scotland’s parliament and is recognised as being a safe
destination. As a modern city, Edinburgh boasts excellent
transport links, with a recently refurbished international
airport as well as first class rail and road access.
Delegates who are able to add a day or two on to their
visit will be delighted to know that the rest of Scotland is
literally on their doorstep. With castles steeped in history,
golf, fishing, skiing, shopping and distillery tours to choose
from, it’s impossible to fit it all in.
Edinburgh is the second-largest city in Scotland and the
country’s capital city. The historic centre of Edinburgh is
divided into two by Princes Street Gardens. To the south
the view is dominated by Edinburgh Castle, perched on
the extinct volcanic crag, and the long sweep of the Old
Town trailing after it along the ridge. To the north lies
Princes Street and the New Town.
Edinburgh is well known for the annual Festival, the
associated Festival Fringe the largest performing arts
festival in the world, and for the Hogmanay street party.
Please visit www.edinburgh.org for more information.
THE VENUE
THE EDINBURGH INTERNATIONAL
CONFERENCE CENTRE (EICC)
The Edinburgh International Conference Centre takes
great pride in being regarded as Scotland’s foremost
conference venue. The EICC has established a reputation for
professionalism, excellence and quality on a global scale.
Positioned in the very heart of a city with history, culture
and heritage, the purpose built spectacular structure
is designed to give maximum flexibility for all types
of occasions.
Please visit www.eicc.co.uk for more information.
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Major Psychoses and Substance Abuse
REGISTRATION
The registration area will be situated in the Strathblane Hall in the EICC. The opening hours are as follows:
Saturday 25th April 2009
Sunday 26th April 2009
Monday 27th April 2009
1400 to 1930
0800 to 1800
0800 to 1600
On Site Entitlements
The delegate registration fee for CINP Members of £475.00 includes:
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Attendance at all Scientific Sessions and Commercial Exhibition
Attendance at the Welcome Reception on Saturday 25th April 2009
Tea/Coffee during official breaks
Lunch on Sunday 26th and Monday 27th April 2009
Delegate Bag, Programme Book and Conference Material
Certificate of Attendance
VAT at prevailing rate
The delegate registration fee for Non Members of £650.00 includes:
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Attendance at all Scientific Sessions and Commercial Exhibition
Attendance at the Welcome Reception on Saturday 25th April 2009
Tea/Coffee during official breaks
Lunch on Sunday 26th and Monday 27th April 2009
Delegate Bag, Programme Book and Conference Material
Certificate of Attendance
VAT at prevailing rate
The delegate registration fee for Young Scientists of £175.00 includes:
(Individuals must have a doctorate degree, be working full-time in neuropsychopharmacology research, teaching, or
clinical activities, have not reached his/her 36th birthday in the year in which the conference takes place (i.e. no older
than 35 years of age as of 31st December 2009).
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•
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Attendance at all Scientific Sessions and Commercial Exhibition
Attendance at the Welcome Reception on Saturday 25th April 2009
Tea/Coffee during official breaks
Lunch on Sunday 26th and Monday 27th April 2009
Delegate Bag, Programme Book and Conference Material
Certificate of Attendance
VAT at prevailing rate
The delegate registration fee for Developing Countries of £75.00 includes:
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•
•
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•
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•
Attendance at all Scientific Sessions and Commercial Exhibition
Attendance at the Welcome Reception on Saturday 25th April 2009
Tea/Coffee during official breaks
Lunch on Sunday 26th and Monday 27th April 2009
Delegate Bag, Programme Book and Conference Material
Certificate of Attendance
VAT at prevailing rate
Collegium Major
Internationale
Psychoses
Neuro-Psychopharmacologicum
and Substance Abuse
55
Contents
CONFERENCE
INFORMATION
Payment of Fees
All prices quoted are in pounds sterling and payments in any other currency will not be accepted. Please remit payment
by either bank draft or cheque payable to CINP/Northern Networking Events Ltd. Fees can also be paid by credit card.
The local organisers will accept payment by Visa, Mastercard, Access and Barclaycard. AMEX is not accepted.
Official Language
The official language for the Conference is English. Simultaneous interpretation services will not be provided.
Catering
Tea/coffee and Lunch at the dedicated times are included in the registration fee.
CME Accreditation
The ‘CINP’ is accredited by the European Accreditation Council for Continuing Medical Education (EACCME) to provide
the following CME activity for medical specialists. The EACCME is an institution of the European Union of Medical
Specialists (UEMS), www.uems.net . The ‘CINP Thematic Meeting’ is designated for a maximum of (or ‘for up to’)
13 hours of European external CME credits. Each medical specialist should claim only these hours of credit that he/she
actually spent in the educational activity.
EACCME credits are recognized by the American Medical Association towards the Physician’s Recognition Award (PRA).
To convert EACCME credit to AMA PRA category 1 credit, contact the AMA.
Cloakroom and Luggage
A cloakroom will be available during the conference for delegates to leave their coats and luggage. The opening times
are:
Saturday 25th April 2009
1400 – 2000
Sunday 26th April 2009 0800 – 2000
Monday 27th April 2009 0800 – 1600
The cloakroom is situated in the Strathblane Hall.
CINP Membership
CINP (Collegium Internationale Neuro-Psychopharmacologicum) is the world’s truly global psychopharmacology
organisation. It is a membership organisation with widespread support from all over the world. Its mission is to
encourage and promote international scientific study, teaching and the application of neuropsychopharmacology. It
also provides advice and consultation for the better evaluation of all aspects of neuropsychiatric drugs, especially the
biochemistry, pharmacology, safety and therapeutic efficacy. Through these activities it seeks to improve and advance
research activities thus leading to improved patient care.
CINP was established in 1957 in Zurich and had its first international congress in Rome in 1958. Since then virtually
all the leading researchers in psychopharmacology have attended the meetings and been involved in the organisation.
Names such as Delay, Deniker, Lehmann, Hippius, Janssen, Coppen and Carlsson are a very important part of the
history of psychopharmacology and of CINP as well. The most exciting and original science in this field has been
associated with CINP in the past and it is the declared intention of the current President, Prof. Robert H. Belmaker, that it
will remain a vital part of CINP now and in the future.
A CINP New membership application form has been inserted into your delegate bag. If you would like to apply to become
a member of CINP please complete and return the form with all the necessary documents to the CINP Central Office.
If you would like further information about CINP please ask at the registration desk.
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Major Psychoses and Substance Abuse
Delegate Feedback Form
CINP would like your feedback regarding the conference. This can include how we can improve the conference and
any relevant topics you would like covered at our next Thematic Meeting. A feedback form has been inserted into your
delegate bag. Please complete and return the feedback form to the conference registration desk or send it to the CINP
Central Office.
Tourist Information
The central Edinburgh and Scotland Information Centre is located at:
3 Princes Street
Edinburgh
EH2 2QP
Web: www.edinburgh.org
Opening times during April are
Monday – Saturday 0900 – 1900
Sunday 1000 - 1900
Smoking
On March 26th 2006 a smoking ban was introduced in all enclosed public spaces in Scotland. This includes
restaurants, bars, nightclubs, shops, cinemas, offices, hospitals, sport centres and airports. Designated smoking areas
have been set up outside many restaurants and bars and should be used accordingly.
Tipping
Although not compulsory, it is generally accepted that you should tip approximately 10-15% in restaurants and 10% to
taxi drivers on longer journeys.
Banks and Cash Dispensers
In general, banking hours in Edinburgh are 0900 – 17.00 hrs Monday to Friday. Some city centre banks are open on
Saturdays from 0900 – 13.00 hrs. Nearly all banks, building societies and post offices offer a foreign exchange service.
As the banks do not have reliable hours at the weekend there is a foreign exchange service located at the Tourist
Information Centre office at 3 Princes Street, Edinburgh and also at Waverley train station in the accommodation kiosk.
PROGRAMME
Saturday 25 April 2009
Time
Pentland Auditorium
14.00 – 19.30
Registration takes place all day in
the Strathblane Hall
17.00 – 18.30
Opening Plenary Session:
“Why look for animal models
of schizophrenia when druginduced psychosis provides
such a good model?”
Chairman: Prof. Robert H.
Belmaker, Israel
Speaker:
Prof. Robin Murray, UK
18.30 – 19.30
Welcome Reception will take place
in the foyer
Collegium Major
Internationale
Psychoses
Neuro-Psychopharmacologicum
and Substance Abuse
77
Contents
PROGRAMME
Sunday 26 April 2009 – Research Day
08.00 – 18.00
Registration - Strathblane Hall
Pentland Auditorium
09.00 –10.00
Sidlaw Room
Fintry Room
Parallel Session 3:
Stimulants
Chairman: Dr Paul Fletcher, UK
Plenary Session 2:
“Addiction and Psychosis as
cortico-striatal syndromes”
Chairman: Prof. Torgny H.
Svensson, Sweden
Speaker:
Prof. Trevor Robbins, UK
10.00 – 10.30
Tea and Coffee – Strathblane Hall
10.30 – 12.00
Parallel Session 1:
Glutamate and cortico-striatal
dysfunction: Implications for
schizophrenia and addiction
Chairman: Dr John Krystal, USA
Parallel Session 2:
Nicotine abuse in schizophrenia –
molecular aspects
Chairman: Prof. Georg Winterer,
Germany
Speakers:
Dr Lars V. Kristiansen, Denmark
“Abnormalities in the glutamate
synapse in schizophrenia”
Speakers: Prof. Georg Winterer,
Germany
“Alpha4 nACh Genotype and
Attentional Network Dysfunction
- Implications for Nicotine
Dependence in Schizophrenia”
Prof. Trevor Robbins, UK
“Stimulant dependence,
compulsivity and dopamine”
Prof. Andreas Heinz, Germany
“Major psychoses and
substance abuse: evidence for
common limbic alterations”
Dr John Krystal, USA
“Opposing alterations in
responses to NMDA receptor
antagonists in schizophrenia
and alcohol dependence:
Implications for addiction risk
and for treatment?”
12.00 – 13.15
Prof. Sherry Leonard, USA
“Nicotine addiction in
schizophrenia: self medication?”
Dr Ingo Vernaleken, Germany
“PET Studies of Dopaminergic
Systems in Nicotine Dependence
and Schizophrenia”
Prof. Dr. Dan Rujescu, Germany
“Variants in the CHRNA5-CHRNA3CHRNB4 gene cluster are associated
with CHRNA5 gene expression and
nicotine dependence in three large
independent German cohorts”
Speakers:
Dr Isabelle Boileau, Canada
“Amphetamine sensitization
in man”
Dr Paul Fletcher, UK
“Ketamine-induced psychoses”
Dr Graham Murray, UK
“Cognition in Parkinson’s
disease psychosis”
Prof. Nori Takei, Japan
“Mechanisms underlying
methamphetamine psychoses”
Dr Tomáš Páleničk, Czech Republic
“From early to present use of
psychedelic drugs such as LSD in
research and psychiatry”
Pfizer Satellite Symposium:
The Links between Smoking
and Psychiatric Disease: What
can be done to help?
Chairman: Prof. Wolfgang
Fleischhacker, Austria
Speakers:
Prof. Georg Winterer, Germany
“An Overview of Smoking and
Psychiatric Disease”
Dr Hans Rollema, Pfizer Groton,
USA “The Mechanisms of Nicotine
Addiction and Approaches to
Overcome it”
Prof. Henri-Jean Aubin, France
“Current Approaches to Smoking
Cessation in Patients with
Psychiatric Disease”
Prof. Torgny H. Svensson, Sweden
“Future Approaches to Smoking
Cessation in Patients with
Psychiatric Disease”
8
Collegium Internationale Neuro-Psychopharmacologicum
Sunday 26 April 2009 – Research Day
13.15 – 14.00
Lunch – Strathblane Hall
14.00 – 15.30
Parallel Session 4:
Two faces of Dopamine
Chairman: Prof. Anissa AbiDargham, USA
Speakers:
Prof. Anissa Abi-Dargham, USA
“Dopamine alterations in
comorbidity”
Dr Christoph Kellendonk, USA
“Excess dopamine D2 receptors in
the striatum affect cognition and
motivation in mice”
Dr Eleanor Simpson, USA
“Modelling endophenotypes for
addiction and schizophrenia in
COMT over-expressing mice”
Prof. Anthony Grace, USA
“Schizophrenia, stress,
and drug abuse: common
pathophysiological mechanisms”
Parallel Session 5:
Hallucinogenic drugs and
psychosis – psychopathology and
brain mechanisms
Chairman: Prof. Euphrosyne
Gouzoulis-Mayfrank, Germany
Parallel Session 6:
Cannabis concerns: the
experimental and sociological
background
Chairman: Prof. Don Linszen, The
Netherlands
Speakers:
Prof. Franz X. Vollenweider,
Switzerland
“Spatiotemporal brain imaging of
visual hallucinations induced by
the 5-HT2A agonist psilocybin in
humans”
Speakers:
Prof. Roger Pertwee, UK
“The endocannabinoid system”
Prof. Bill Deakin, UK
“Glutamate and the origin and
progression of psychosis”
Dr Garry D. Honey, UK
“Applying pharmalogial models of
psychosis to understand cognitive
and physiological mechanisms
associated with schizophrenia”
Dr David Potter, UK
“Increasing Cannabis potency”
Prof. Valerie Curran, UK
“Differential effects on THC and
CBD in “normal” cannabis smokers”
Dr Paul Morrison, UK
“Acute effects of Intravenous THC”
Dr Judith Allardyce, The Netherlands
“Epidemiological Studies of
Cannabis and Psychosis”
Dr Joerg Daumann, Germany
“Attention Processes and its Brain
Mechanisms in the Human 5-HT2A
Agonist and NMDA Anta-gonist
Model of Psychosis”
15.30 – 16.00
Tea and Coffee – Strathblane Hall
16.00 – 17.30
Parallel Session 7:
Cannabis use and the
presentation and outcome of
psychosis
Chairman: Prof. Robin Murray, UK
Speakers:
Prof. Philip McGuire, UK
“A functional MRI study of the
effects of cannabis”
Parallel Session 8:
Clozapine and comorbid
substance abuse in
schizophrenia: Mode of action
and novel leads
Chairman: Prof. Torgny H. Svensson,
Sweden
Prof. Don Linszen, The
Netherlands
“Clinical studies of cannabis use”
Speakers:
Prof. Torgny H. Svensson, Sweden
“Significance of alpha2
adrenoceptor blockade and NET
inhibition for antipsychotic drug
effects”
Dr Marta di Forti, UK
“Skunk and Psychosis in South
East London”
Dr Svante Nyberg, Sweden
“A translational perspective on
quetiapine - clinical utility”
Dr Cathy Fernandes, UK
“Modelling the effects of cannabis
in adolescent mice”
Prof. Alan I. Green, USA
““A Translational Perspective on
Clozapine: Clinical Utility”
Parallel Session 9:
Alcohol
Chairman: Prof. Andreas Heinz,
Germany and Prof. Gunter
Schumann, UK
Speakers:
Prof. Gunter Schumann, UK
“Genetic findings in alcoholism role of the glutamatergic system”
Prof. Rainer Spanagel, Germany
“Metabotropic glutamate receptors
and alcohol seeking and relapse”
Dr Florian Schlagenhauf, Germany
“Reward system dysfunction in
alcoholism and schizophrenia”
Dr Wiepke Cahn., The Netherlands Prof. Helen M. Pettinati, USA
“Cannabis use and progression of “A double-blind, placebo-controlled
brain changes”
pilot trial of quetiapine for the
treatment of Type A and Type B
alcoholism”
17.30 – 19.00
Poster Session – Strathblane Hall
Major Psychoses and Substance Abuse
9
Contents
Monday 27th April 2009 – Education Day
08.00 – 16.00
Registration – Strathblane Hall
Pentland Auditorium
09.00 – 10.00
Sidlaw Room
Fintry Room
Study Group 2:
ETOH
Chairman: Prof. Andreas Heinz,
Germany
Study Group 3:
Nicotine abuse in schizophrenia
Chairman: Prof. Georg Winterer,
Germany
Speakers:
Dr Florian Schalgenhauf, Germany
“Reduced activation during reward
anticipation in the ventral striatum
correlates with impulsivity in
alcoholics”
Speakers:
Prof. Tony P. George, Canada
“Translating Neuroscience to
Tobacco Treatment in Schizophrenia:
The Devil is in the Details!”
Plenary Session 3:
Schizophrenia and Substance
Abuse: Approaching
Pharmacotherapy
Chairman: Prof. Wolfgang
Fleischhacker, Austria
Speaker:
Prof. Alan I. Green, USA
10.00 – 10.30
Tea Coffee – Strathblane Hall
10.30 – 12.00
Study Group 1:
Cannabis use and the
presentation and outcome of
psychosis
Chairman: Prof. Robin Murray, UK
Speakers:
Dr Zerrin Atakan, UK
“Cannabis use in those with
severe mental illness: what can
be done?
Dr Wiepke Cahn, The Netherlands
Prof. Rainer Spanagel, Germany
“Alcoholism – A Systems Approach
from Molecular Physiology to
Addictive Behaviour”
Prof. Juergen Gallinat, Germany
“Brain imaging”
Prof. Michael Wagner, Germany
“Nicotine self-medication: beyond
schizophrenia”
Prof. Veena Kumari, UK
“Possible Mechanisms Mediating
the Association between Smoking
and Schizophrenia”
12.00 – 14.00
Lunch – Strathblane Hall
14.00 – 15.30
Study Group 5:
Bipolar
Speaker:
Prof. Robert H. Belmaker, Israel
“Bipolar disorder
and substance abuse”
Study Group 6:
Chronic psychosis
Chairman: Prof. Alan I. Green, USA
Study Group 7:
Substance-induced psychosis
Chairman: Dr Carol Caton, USA
Speakers:
Dr Mary Brunette, USA
Speakers:
Dr Euphrosyne Gouzoulis-Mayfrank,
Germany
“Substance induced psychosis
vs. dual diagnosis: Diagnostic
considerations – The case of
hallucinogens and stimulants”
Prof. Tomas Palomo, Spain
Prof. Don Linszen, The Netherlands
Prof. Andreas Heinz, Germany
“Clinical aspects of dopamineinduced psychoses and their
implications for the dopamine
hypothesis of schizophrenia”
Prof. Michael First, USA
“ Substance use and psychosis:
Diagnostic challenges and a case
of “Polysubstance Abuse”
10
Major Psychoses and Substance Abuse
Abstracts and Biographies
SATURDAY 25TH APRIL
Saturday 25th April 2009 17.00 – 18.30 Pentland Auditorium
Chairman: Prof. Robert H. Belmaker, Israel
Opening Plenary Session: Why look for animal models of schizophrenia when
drug-induced psychosis provides such a good model?
Prof. Robin Murray, UK
Abstract
There is widespread evidence that people diagnosed as
having schizophrenia-like psychoses are more likely to use
illicit drugs than the populations from which they are drawn.
Two types of drugs have been particularly implicated,
the amphetamines and cannabis. Methamphetamine
psychosis has reached epidemic proportions in certain
Pacific countries and has been growing in frequency
in North America. The clinical picture shows a close
resemblance to the positive symptoms of schizophrenia
but often resolves within a few days or weeks. It appears
to be a consequence of dopamine sensitization, and is
most likely to occur in those methamphetamine abusers
who have a schizoid or schizotypal personality and in
those with a familial predisposition to psychosis. So far,
however, it has not been possible to identify predisposing
genes. Cannabis is the most widely abused illicit drug in
the world, and has been causing some concern because
of a) the general increase in consumption over the last
25 years, and b) increased potency of street preparations
available in many countries. Among those with
established psychosis, its consumption results in a worse
outcome. In addition, over the past 7 years, a series of
cohort studies have produced evidence that regular use
of cannabis increases the risk of schizophrenia in a dose
related manner. Current research addresses the question
of whether this effect is mediated by dopamine, whether
variation at the COMT locus influences vulnerability to
both acute and chronic psychosis, and whether skunk has
a greater detrimental effect.
Biography
Robin Murray received his medical degree from the
University of Glasgow, Scotland, and trained in Internal
Medicine there. He then came to study psychiatry at the
Maudsley Hospital in London and has remained there
ever since, apart from 1 year as MRC Fellow at NIH in
Washington. He was Dean of the Institute of Psychiatry and
is now Professor of Psychiatry there; he tries, not always
successfully, to avoid drowning in University Committees.
According to ISI he is the second most widely cited
psychiatric researcher in the world livng outside the USA.
His special interest is in the understanding and treatment
of psychotic illnesses, and he lookos after people with
these illnesses.
Collegium Major
Internationale
Psychoses
Neuro-Psychopharmacologicum
and Substance Abuse
11
11
Abstracts and Biographies
SUNDAY 26TH APRIL
Sunday 26th April 2009 Chairman: Prof. Torgny H. Svensson, Sweden
09.00 – 10.00 Pentland Auditorium
Plenary Session 2: Addiction and Psychosis as cortico-striatal syndromes
Prof. Trevor Robbins, UK
Abstract
Addiction, particularly to stimulant drugs such as
amphetamine and cocaine, and psychosis such as
occurs in schizophrenia, share the dysregulation of
some common neural substrates, particularly as regards
the dopamine-dependent functions of the so-called
fronto-striatal ‘loop circuitry’. Recent neuroimaging
evidence has revived the concept of a hyperactive
striatal dopamine system, even in early schizophrenia,
although its origins are still unclear. This state has been
assumed to lead to an enhancement of the salience
of environmental stimuli which engages processes of
attribution that lead to delusional phenomena that can
be ‘extinguished’ by dopamine D2 receptor blockade. It
might be surmised that an up-regulation of dopamine
by drugs such as cocaine and amphetamine similarly
enhances the incentive salience of environmental stimuli,
leading to drug-seeking and taking behaviour, although
paranoid behaviour is another occasional outcome. I will
consider the implications of this formulation of deficits in
incentive learning for the understanding of both psychosis
and reward-related behaviour. In both cases, it is likely
that cortico-limbic afferents modulate the regulation of
striatal dopamine. In the case of schizophrenia, cortical
damage may provide the impetus for striatal dopamine
up-regulation as well as aberrant associative learning.
Addiction itself can be considered as a product of aberrant
conditioning in limbic-striatal networks. Possible damage
to frontal cortex and associated regions can serve to
exacerbate the drive to addiction as well as producing a
cognitive deficit syndrome qualitatively sometimes similar
to that observed in schizophrenia. The implications of
these observation will be discussed.
12
Biography
Trevor Robbins was appointed in 1997 as the Professor of
Cognitive Neuroscience at the University of Cambridge.
He was elected to the Chair of Experimental Psychology
(and Head of Department) at Cambridge from October
2002. He is also Director of the Cambridge University
Behavioural and Clinical Neuroscience Institute (MRC and
Wellcome Trust-funded), the main mission of which is to
inter-relate basic and clinical research in neuropsychiatry
and neurology. Trevor has been President of the European
Behavioural Pharmacology Society (1992-1994) and he
won that Society’s inaugural Distinguished Achievement
Award in 2001. He was also President of the British
Association of Psychopharmacology from 1996 to 1997.
He has edited the journal Psychopharmacology since
1980 and joined the editorial board of Science in Jan.
2003. He is a Fellow of the British Psychological Society,
the Academy of Medical Sciences and the Royal Society,
the most prestigious scientific body in the U.K. He was a
member of the Medical Research Council (UK) and chaired
the Neuroscience and Mental Health Board from 1995
until 1999. He is on a list of the most cited neuroscientists
by ISI, publishing over six hundred full-length articles in
books or scientific journals. He has co-edited four books
(Psychology for Medicine: The Prefrontal Cortex; Executive
and Cognitive Function: Disorders of Brain and Mind: and
Drugs and the Future). The latter was based on the U.K.
Technology Foresight Project on Brain Science, Addiction
and Drugs, for which Dr. Robbins was co-leader. He
shared the IPSEN Fondation Prize in Neuronal Plasticity
in 2005 and was the Kavli Distinguished International
Scientist Lecturer at the Society for Neuroscience annual
meeting that year.
Collegium Internationale Neuro-Psychopharmacologicum
Sunday 26th April 2009 Chairman: Dr John Krystal, USA
10.30 – 12.00 Pentland Auditorium
Parallel Session 1: Glutamate and cortico-striatal dysfunction:
Implications for schizophrenia and addiction
Dr Lars V. Kristiansen, Denmark
Abnormalities in the glutamate synapse in schizophrenia
Abstract
The involvement of glutamate in the pathophysiology
of schizophrenia is evident from numerous studies. The
glutamate synapse consists of a complex organization
of receptors, transporters and intracellular proteins with
specialized roles in the functional regulation of excitatory
neurotransmission. Studies in postmortem brain have
identified altered expression of several molecules
associated with the pre- and postsynaptic compartments,
as well as the associated neuroglia. This includes
substantial findings of altered expression of molecules
associated with the postsynaptic density (PSD). In particular,
recent studies have found altered expression in PFC of
markers for cellular processing of the NR2B-containing
type of N-methyl-D-Aspartate (NMDA) receptors,
indicating altered cellular handling of this receptor
subtype in schizophrenia. Further insight into subtype
specific changes of NMDA receptor processing might
lead to improved understanding of specific symptoms of
schizophrenia including cognitive dysfunction.
Biography
Dr. Kristiansen received his M.Sc. and Ph.D. in Human
Biology and Health Sciences from the University of
Copenhagen. After finishing his Ph.D. in 2004, Lars
Kristiansen started his postdoc with Dr. James MeadorWoodruff at the University of Michigan and in 2006
moved with Dr. Meador-Woodruff to the Department of
Psychiatry and Neurobiology at the University of Alabama
at Birmingham, where he continued his studies of markers
for altered glutamate function in postmortem brain from
patients with schizophrenia. At the end of 2008 Dr.
Kristiansen returned to his native country Denmark for a
position as research faculty at the Bispebjerg University
Hospital in Copenhagen. In Collaboration with Professor
Bente Pakkenberg at the Research Laboratory for
Stereology and Neuroscience, Dr. Kristiansen is involved
in establishing a molecular research program with a
continued research focus on the molecular biology of
glutamate dysfunction in schizophrenia.
Major Psychoses and Substance Abuse
13
Abstracts and Biographies
Sunday 26th April 2009 Chairman: Dr John Krystal, USA
10.30 – 12.00 Pentland Auditorium
Parallel Session 1: Glutamate and cortico-striatal dysfunction:
Implications for schizophrenia and addiction
Prof. Trevor Robbins, UK
Stimulant dependence, compulsivity and dopamine
Abstract
TW Robbins (with KD Ersche and ET Bullmore). Behavioural
and Clinical Neuroscience Institute, Depts. of Expt.
Psychology and Psychiatry, University of Cambridge
There are no effective pharmacotherapies for stimulant
dependence but there are many plausible targets for
development of novel therapeutics. We hypothesized that
dopamine-related targets are relevant for treatment of
stimulant dependence, and there are likely to be individual
differences in response to dopaminergic challenges. We
measured behavioral and brain functional markers of
drug-related attentional bias in stimulant-dependent
individuals, studied repeatedly after acute dosing with
dopamine D2/D3 receptor antagonist and agonist
challenges. The design was a randomized, doubleblind, placebo-controlled, parallel groups, cross-over
design using pharmacological fMRI. The participants
were stimulant-dependent individuals (n=18) and
healthy volunteers (n=18). Amisulpride (400 mg),
pramipexole (0.5 mg), or placebo were administered in
counterbalanced order at each of three repeated testing
sessions. Attentional bias for stimulant-related words was
measured during fMRI by a drug-word Stroop paradigm;
trait impulsivity and compulsivity of dependence were
assessed at baseline by questionnaire. The drug users
demonstrated significant attentional bias for drug-related
words, which was correlated with greater activation of
left ventral prefrontal cortex. Attentional bias was greater
in people with highly compulsive patterns of stimulant
abuse; the effects of dopaminergic challenges on
attentional interference and related prefrontal activation
were different between high and low compulsivity subgroups. We propose that greater attentional bias for, and
greater prefrontal activation by, stimulant-related words
is a candidate neurocognitive marker for dependence.
Individual differences in compulsivity of stimulant
dependence had significant effects on attentional bias, its
frontal cortical representation, and its acute modulation by
dopaminergic challenges. The more general implications
of these data will be considered for other forms of
psychopathology, including psychosis.
14
Biography
Trevor Robbins was appointed in 1997 as the Professor of
Cognitive Neuroscience at the University of Cambridge.
He was elected to the Chair of Experimental Psychology
(and Head of Department) at Cambridge from October
2002. He is also Director of the Cambridge University
Behavioural and Clinical Neuroscience Institute (MRC and
Wellcome Trust-funded), the main mission of which is to
inter-relate basic and clinical research in neuropsychiatry
and neurology. Trevor has been President of the European
Behavioural Pharmacology Society (1992-1994) and he
won that Society’s inaugural Distinguished Achievement
Award in 2001. He was also President of the British
Association of Psychopharmacology from 1996 to 1997.
He has edited the journal Psychopharmacology since
1980 and joined the editorial board of Science in Jan.
2003. He is a Fellow of the British Psychological Society,
the Academy of Medical Sciences and the Royal Society,
the most prestigious scientific body in the U.K. He was a
member of the Medical Research Council (UK) and chaired
the Neuroscience and Mental Health Board from 1995
until 1999. He is on a list of the most cited neuroscientists
by ISI, publishing over six hundred full-length articles in
books or scientific journals. He has co-edited four books
(Psychology for Medicine: The Prefrontal Cortex; Executive
and Cognitive Function: Disorders of Brain and Mind: and
Drugs and the Future). The latter was based on the U.K.
Technology Foresight Project on Brain Science, Addiction
and Drugs, for which Dr. Robbins was co-leader. He
shared the IPSEN Fondation Prize in Neuronal Plasticity
in 2005 and was the Kavli Distinguished International
Scientist Lecturer at the Society for Neuroscience annual
meeting that year.
Collegium Internationale Neuro-Psychopharmacologicum
Sunday 26th April 2009 Chairman: Dr John Krystal, USA
10.30 – 12.00 Pentland Auditorium
Parallel Session 1: Glutamate and cortico-striatal dysfunction:
Implications for schizophrenia and addiction
Prof. Andreas Heinz, Germany
Major psychoses and substance abuse: evidence for common limbic alterations
Abstract
Andreas Heinz
Department of Psychiatry and Psychotehrapy, Charité –
University Medical Center, Berlin
Alcohol dependence displays high comorbidity with
schizophrenia and bipolar disorders. While some patients
may simply use alcohol as a kind of slef-medication that
runs out of control, the vulnerability for exactly this loss
of control may in part be attributable to alterations in
limbic systems that contribute both to the risk to develop
drug abuse and schizophrenia. Particularly, phasic and
potentially stress-induced dysregulation of subcortical
dopamine release in schizophrenia may sensitize patients
towards the dopaminergic effects of alcohol and other
drugs of abuse. Indeed, dysfunction of functional activation
of the brain reward system during reward anticipation
was found in patients suffering form alcohol dependence
and schizophrenia. Patients with schizophrneic psychosis
appear to also display alterations in neuronal procesing
of punishment, which may help to explain the vulnerability
for some more complex symptoms such as anxious
feelings of persecution. The implications of these findings
for pharmacotherapy will be discussed.
Biography
Andreas Heinz, MD, studied medicine, philosophy and
anthropology at the Ruhr-Universität Bochum, Freie
Universität Berlin and Howard University, Washington
DC. Clinical education in neurology, psychiatry and
psychotherapy; research focus on reward system function
and dysfunction in alcoholism and schizophrenia and
on social and transcultural psychiatry. 2000 elected as
associate professor for addiction research, University
of Heidelberg, 2002 full professor, director and chair,
Charité - University Medical Center Berlin.
Major Psychoses and Substance Abuse
15
Abstracts and Biographies
Sunday 26th April 2009 Chairman: Dr John Krystal, USA
10.30 – 12.00 Pentland Auditorium
Parallel Session 1: Glutamate and cortico-striatal dysfunction:
Implications for schizophrenia and addiction
Dr John Krystal, USA
Opposing alterations in responses to NMDA receptor antagonists in schizophrenia
and alcohol dependence: Implications for addiction risk and for treatment?
Abstract
This presentation will briefly review evidence that
schizophrenia is associated with deficits in NMDA
glutamate receptor function, while alcohol dependence is
associated with enhancement in NMDA glutamate receptor
function. It will review multiple lines of evidence, ranging
from genetics to psychopharmacology, suggesting that
schizophrenia is associated with reduced NMDA receptor
function. In contrast, this presentation will also review
evidence that alcohol dependence is associated with
upregulation in NMDA receptor function. This upregulation
is, in part, a neuroadaptation to ethanol, which is an
NMDA receptor antagonist. However, the familial risk for
alcoholism also may be associated with enhanced NMDA
receptor function, as reflected by reduced responsivity
to NMDA receptor antagonist administration. How do
we, then, understand the increased risk for alcoholism
among individuals diagnosed with schizophrenia?
Through mechanisms not well understood, individuals
with schizophrenia and individuals at risk for developing
alcoholism show similar disturbances in reward/
motivation circuitry. However, the increased sensitivity
to the NMDA receptor antagonist effects of ethanol
may explain the reduced levels of alcohol consumption
among patients diagnosed with both schizophrenia and
alcoholism compared to alcohol dependent individuals
without schizophrenia. Possible treatment implications of
altered NMDA receptor regulation for the group of dually
diagnosed patients will be briefly considered.
16
Biography
Dr. Krystal is the Robert L. McNeil, Jr., Professor of Clinical
Pharmacology and Deputy Chairman for Research for
the Department of Psychiatry, Yale University School of
Medicine and the VA Connecticut Healthcare System. He
is a graduate of the University of Chicago, Yale University
School of Medicine, and the Yale Department of Psychiatry
Residency Training Program. He has published over 300
papers and chapters on the neurobiology and treatment
of alcoholism, schizophrenia, and post-traumatic stress
disorder. In this work, he is best known for studies of
the contributions of amino acid neurotransmission to
behavior, cognition, psychopathology, and treatment.
His research program unites psychopharmacology,
neuroimaging, and molecular genetics. He is principal
investigator of the NIAAA Center for the Translational
Neuroscience of Alcoholism, VA Alcohol Research Center,
and Clinical Neuroscience Division of the VA National
Center for PTSD. Dr. Krystal received the Joel Elkes Award
of the American College of Neuropsychopharmacology
(ACNP), the Han Jönas Weitbrecht Scientific Award from
Bayer, the APIRE/Kempf Fund Award of the American
Psychiatric Association, Most Highly Cited Investigator
Award from Thomson-ISI, and other awards. He was
Chairman of the NIMH Board of Scientific Counselors
(2004-2007) and he currently serves on the NIAAA
National Alcohol Advisory Council. He also serves on
the NARSAD Scientific Advisory Board and the boards
of directors of the ACNP and the Research Society on
Alcoholism. He was a managing editor for the journal,
Psychopharmacology (1999-2006) and is currently editor
of Biological Psychiatry.
Collegium Internationale Neuro-Psychopharmacologicum
Sunday 26th April 2009 Chairman: Prof. Georg Winterer, Germany
10.30 – 12.00 Sidlaw Room
Parallel Session 2: Nicotine abuse in schizophrenia – molecular aspects
Prof. Georg Winterer, Germany
Alpha4 nACh Genotype and Attentional Network Dysfunction - Implications for
Nicotine Dependence in Schizophrenia
Abstract
Different mutations on chromosome 20q13.2, located
in exon 5 of the CHRNA4 (gene coding for subunit 4 of
the nicotinic acetylcholine receptor), have been identified
in autosomal dominant nocturnal frontal lobe epilepsy
(ADNFLE). Most ADNFLE patients were found to have an
unusual high rate of serious psychiatric disorders with
mostly psychosis or schizophrenia-like clinical features and
cognitive deficits. On the other hand, single nucleotide
polymorphisms (SNPs) in CHRNA4 exon 5 have been
repeatedly associated with nicotine dependence. Nicotine
dependence itself is a frequent finding in schizophrenia
and there is emerging evidence from different sides that
schizophrenia patients use nicotine – in part - for selftreatment of attentional deficits which are among the
most prominent cognitive deficits in this illness. Attentional
performance in turn has been associated with SNPs in
CHRNA4 exon 5. In our talk, we will give a brief overview on
this matter including most recent findings from the German
research network on nicotine dependence: http://www.
nicotine-research.com
Biography
Prof. Dr. Georg Winterer *1961
Since 2006 Full Professor of Psychiatry
/Clinical Director
Dept. of Psychiatry, Univ. of Düsseldorf/
Inst. of Neurosciences & Biophysics,
Helmholtz Research Center Jülich
2003-2005 Senior Researcher, Psychiatry,
Univ. of Mainz/Düsseldorf,
Clinical Genetics, MR Imaging,
Electrophysiology
1998-2003 Research Fellow, National Institute
of Mental Health, Clinical Brain
Disorders Branch/ National Institute of
Alcohol Abuse & Alcoholism,
Neurogenetics Laboratory
(Bethesda, USA): Clinical Genetics,
MR Imaging, Electrophysiol.
2001
Habilitation (PhD):
“Physiology of Prefrontal Function”
1995-1998 Postdoc, Lab. of Psychophysiology,
Dept. of Psychiatry, Free Univ. Berlin:
Electrophysiology, Clinical Genetics
1991
1990-1995
Doctoral Thesis
“Reaction to Aversive Stimuli”
Clinician and Junior Research Fellow,
Dept. for Psychiatry, Free Univ. Berlin
Research Fields
Clinical Genetics, Functional Imaging, Schizophrenia,
Addiction. My major interest is how dopaminergic/
nicotinergic function and its genetic variations are related to
prefrontal function in schizophrenia and addiction. My lab is
among the very few sites being able to conduct simultaneous
fMR-Imaging/Electrophysiology. Apart from conventional
analyses, EEG-informed fMRI-analysis, structural equation
modelling, neural network analysis and independent
component analysis are the tools we are using to integrate
functional data with molecular and genetic information.
Selected Publications
Breitling,L.P., Dahmen, N., Mittelstraß, K., Rujescu, D.,
Gallinat, J., Fehr, C., Giegling, I., Lamina, C., Illig, T., Müller,
H., Raum, E., Rothenbacher, D., Wichmann, H.-E., Brenner,
H., Winterer, G. (2009) Association of nicotinic acetylcholine
receptor subunit alpha-4 polymorphisms with nicotine
dependence in 5500 Germans. Pharmacogenomics J
(in press)
Rolls, E.T., Loh, M., Deco, G., Winterer, G. (2008)
Schizophrenia and computational models of dopamine
modulation in the prefrontal cortex. Nature Reviews
Neuroscience 9:696-709
Mobascher, A., Brinkmeyer, J., Warbrick, T., Musso, F.,
Wittsack, H.J., Saleh, A., Schnitzler, A., Winterer, G.
(2009) Laser-evoked potential P2 single-trial amplitudes
covary with the fMRI BOLD response in medial pain system
and interconnected subcortical structures. NeuroImage
144:1081-92
Javitt, D., Spencer, K.M., Thaker, G.K., Winterer, G.,
Hajos, M. (2008) Biomarkers for schizophrenia – Novel
approaches to diagnosis and treatment. Nature Reviews
Drug Discovery 7:68-83.
Winterer, G., Musso, F., Konrad, A., Vucurevic, G., Stoeter,
P., Sander, T., Gallinat, J. (2007) Association of attentional
network function and exon 5 variations of the CHRNA4
gene. Human Molecular Genetics 16:2165-2174.
Major Psychoses and Substance Abuse
17
Abstracts and Biographies
Sunday 26th April 2009 Chairman: Prof. Georg Winterer, Germany
10.30 – 12.00 Sidlaw Room
Parallel Session 2: Nicotine abuse in schizophrenia – molecular aspects
Prof. Sherry Leonard, USA
Nicotine addiction in schizophrenia: self medication?
Abstract
Most schizophrenics are heavy users of tobacco
products. More than 80% of patients smoke compared
to approximately 25% of the general population. It has
been proposed that smoking in schizophrenics may
represent a form of self-medication. Schizophrenics use
high-tar cigarettes and extract more nicotine by inhaling
deeper and smoking the cigarette more completely.
Nicotine, administered as either gum or in cigarettes,
has been found to normalize a common auditory sensory
processing deficit, the P50 deficit and also to improve
eye-tracking abnormalities. Recent data suggests that
cognitive deficits may also be improved by smoking in
patients. Schizophrenics express lower levels of nicotinic
receptors in both postmortem brain and in peripheral
blood leukocytes, suggesting that they might be smoking
to stimulate this reduced receptor level. These receptors
flux calcium, resulting in downstream effects on gene
expression. Utilizing microarray-based analysis, we have
evaluated gene expression in postmortem hippocampus
from control and schizophrenic smokers and nonsmokers. Expression of more than 250 genes was
changed in brain of smokers, including genes expressed
in excitatory NMDA pathway. In schizophrenic smokers,
however, regulation of gene expression was not the same
as in controls. We found that smoking in these patients,
again including genes in the NMDA postsynaptic
density, differentially regulated 77 genes. The pattern of
regulation was generally the same. Levels of mRNA for
specific genes, including NCAM, calcineurin A gamma,
and the alpha 7 nicotinic acetylcholine receptor subunit
were aberrant in schizophrenic non-smokers and were
brought to control levels, or normalized, in schizophrenic
smokers. These findings are consistent with a hypothesis
of self-medication by smoking. However, nicotine has
adverse side-effects, and better drugs are needed. We
have completed a Phase I trial for DMXB-A, a partial
agonist at the alpha 7 nicotinic receptor. The results
show improved attention and normalization of sensory
processing deficits in non-smoking patients.
Biography
Sherry Leonard, Ph.D.
Professor
Dr. Nancy Gary Professor in Children’s Mental Disorders
Research
Departments of Psychiatry and Pharmacology, and the
Veterans Administration
University of Colorado Denver
Mail Stop 8344, P. O. Box 6511
Aurora, Colorado 80045
303-724-4426
303-724-4425
E-mail: [email protected]
Description of Research:
Research in my laboratory focuses on the molecular
neurobiology of neuronal nicotinic acetylcholine receptors
in nicotine addiction, and mental illness. These subjects
are intimately related as smoking is significantly elevated
in the mentally ill, particularly in schizophrenia. Nicotinic
receptors are decreased in number in schizophrenic
postmortem brain and are not up regulated in the same
manner as in control smokers. The α7 nicotinic receptor
subunit is a focus in the laboratory. We have cloned both a
human cDNA and the α7 gene. The gene has a complex
structure, including a partial duplication which is currently
being studied in the laboratory. A small deletion (2bp)
in the gene duplication is associated with smoking in
schizophrenia. Mutation screening of the coding region and
core promoter of the full-length gene, CHRNA7, revealed
a complex of polymorphic patterns in the promoter. Many
of these polymorphisms decrease transcription from a
reporter gene in vitro. The functional polymorphisms
analyzed thus far are associated with schizophrenia and
with a decrease in inhibition of the P50 auditory evoked
potential gating response, suggesting that the promoter
variants may play an important role in sensory processing
deficits in schizophrenia. Additional regulatory regions,
including a repressor element upstream, splice variants,
and an intronic enhancer are under investigation.
continued…
18
Collegium Internationale Neuro-Psychopharmacologicum
We have completed an Affymetrix GeneChip expression
study in postmortem hippocampus of control and
schizophrenic smokers and non-smokers. More than
250 genes were changed in expression by smoking and
77 genes were differentially regulated by smoking in
schizophrenic brain. The gene groups most significantly
affected were genes expressed in the NMDA-postsynaptic
density (PSD) and genes in the immune system. Gene
expression in the NMDA-PSD was generally up-regulated
in smokers, but several genes, including calcineurin Aγ,
α-catenin and the α7 nicotinic acetylcholine receptor
were differentially regulated in brain of schizophrenic
subjects by smoking. Expression of genes was lower than
controls in non-smoking schizophrenics and brought to
control levels or normalized by smoking. This suggests a
form of self-medication in the patients and that nicotine
addiction may be quite different in the mentally ill than
in normal smokers with no history of mental illness. The
α7nAChR also has roles in the periphery where it appears
to regulate inflammation and stress responses, also under
investigation in the laboratory.
Reference List
Leonard S, Adler LE, Benhammou K, Berger R, Breese CR,
Drebing C, Gault J et al (2001): Smoking and mental
illness. Pharmacol.Biochem.Behav. 70:
Gault J, Hopkins J, Berger R, Drebing C, Logel J, Walton
K, Short M et al (2003): Comparison of polymorphisms in
the a7 nicotinic receptor gene and its partial duplication
in schizophrenic and control subjects. Am J.Med.Gen.
123B: 39-49.
Leonard S, Gault J, Hopkins J, Logel J, Vianzon R, Short M,
Drebing C et al (2002): Association of promoter variants
in the alpha 7 nicotinic acetylcholine receptor subunit
gene with an inhibitory deficit found in schizophrenia.
Archives of General Psychiatry 59: 1085-1096.
Leonard S (2003): Consequences of low levels of
nicotinic acetylcholine receptors in schizophrenia for drug
development. Drug Development
Mexal S, Frank MG, Berger R, Adams CE, Ross RG,
Freedman R, Leonard S (2005): Differential modulation
of gene expression in the NMDA postsynaptic density
of schizophrenic and control smokers. Molecular Brain
Research 139:317-332.
Leonard, S. and Freedman, R. (2006) Genetics of
chromosome 15q in schizophrenia. Biological Psychiatry
60:115-122.
Ann Olincy, Josette G. Harris, Lynn L. Johnson, Vicki
Pender, Susan Kongs, Diana Allensworth, Jamey Ellis,
Gary O. Zerbe, Sherry Leonard, Karen E. Stevens, James
O. Stevens, Laura Martin, Lawrence E. Adler, Ferenc Soti,
William R. Kem & Robert Freedman. (2006) Proof-ofconcept trial of an α7-nicotinic agonist in schizophrenia.
Arch. Gen. Psych. 63:630-638.
Leonard, S., Mexal, S., Freedman, R. (2007) Smoking,
genetics and schizophrenia: Evidence for self medication.
J. Dual Diagnosis 3:43-59.
Mexal, S., Berger, R., Pearce, L., Barton, A., Logel,
J., Adams, C.E., Ross, R.G., Freedman, R., Leonard,
S. Regulation of a novel αN-catenin splice variant in
schizophrenic smokers. (2008) Am J. Med. Gen. Part B,
147B:759-768.
Stephens, S.H., Logel, J., Barton, A., Franks, A., Schultz,
J., Short, M., Dickenson, J., James, B., Fingerlin, T.E.,
Wagner, B., Hodgkinson, C., Graw, S., Ross, R.G.,
Freedman, R., Leonard, S. (2009) Association of the
5’-upstream regulatory region of the α7 nicotinic
acetylcholine receptor subunit gene (CHRNA7) with
schizophrenia. Schiz. Res., In press.
Major Psychoses and Substance Abuse
19
Abstracts and Biographies
Sunday 26th April 2009 Chairman: Prof. Georg Winterer, Germany
10.30 – 12.00 Sidlaw Room
Parallel Session 2: Nicotine abuse in schizophrenia – molecular aspects
Dr Ingo Vernaleken, Germany
PET Studies of Dopaminergic Systems in Nicotine Dependence and Schizophrenia
Abstract
Vernaleken, Ingo
RWTH Aachen University
Dopaminergic pathomechanisms are discussed in
Schizophrenia as well as in substance-dependency.
Furthermore, both of the diseases show high levels
of comorbidity, especially nicotine dependency can
be diagnosed in most of the patients suffering from
schizophrenia. PET provides a suitable tool for imaging
pre- and postsynaptic functions and structures. In
schizophrenia, increased D2-receptor availability and
an extensively increased striatal dopamine turn-over
in addition to elevated dopamine synthesis capacity
suggest decontrolled dopamine regulation and function;
prefrontal D1-mediated transmission also appears to be
affected. These data will be compared to PET-results of
nicotine dependence to determine pathophysiological
links between these strongly associated diseases.
Biography
Academic appointments
May 1989
High school degree (Abitur)
May 1998
Preliminary medical license
November 1999 Full medical license
December 2000 Medical Doctor (Dr.med.)
Research fellowship
1995-2000
Institute for Toxicology
University of Saarland
(Prof. Dr. Hans H. Maurer)
Field of research:
Metabolism and toxicological
detection of the amphetamine
like anorectic mefenorex in human
urine by gas chromatography
mass spectrometry and
fluorescence polarization
Residencies and positions:
1998 - 2005
Assistant doctor and research
fellow Department of Psychiatry
Johannes Gutenberg University,
Mainz, Germany
20
Since 2005
Senior physician
Department of Psychiatry and
Psychotherapy RWTH Aachen
University Aachen Germany
Since 2009
Assistant professor RWTH Aachen
University Jülich-Aachen Research
Alliance (JARA)
Since 2006
Secretary of the WFSBP Task Force
on Brain Imaging
Licensure and certification:
1999OPD (Operationalized
psychodynamic diagnostics)
2001-2004
IFKV-Curriculum of Psychotherapy
Awards
1999Organon-Poster-Award at 21st
AGNP-meeting Nuremberg, October 9th, 1999
2008
Bursary Young Scientist Award
for poster:
Vernaleken I, Eickhoff S,
Veselinovic T, Klomp M,
Spreckelmeyer K, Schaefer WM,
Gründer G
“Elevated D2/3-Receptor
Availability in Schizophrenia:
An [18F]Fallypride Study”
At “Neuroreceptor Mapping 2008”
meeting Pittsburgh, 17-20.08.2008
Professional societies
AGNP (Arbeitsgemeinschaft für
Neuropsychopharmakologie)
DGBP (Deutsche Gesellschaft für Biologische
Psychiatrie)
DGPPN (Deutsche Gesellschaft für Psychiatrie,
Psychotherapie und Nervenheilkunde)
Collegium Internationale Neuro-Psychopharmacologicum
Sunday 26th April 2009 Chairman: Prof. Georg Winterer, Germany
10.30 – 12.00 Sidlaw Room
Parallel Session 2: Nicotine abuse in schizophrenia – molecular aspects
Prof. Dr. Dan Rujescu, Germany
Variants in the CHRNA5-CHRNA3-CHRNB4 gene cluster are associated with
CHRNA5 gene expression and nicotine dependence in three large independent
German cohorts
Abstract
D. Rujescu , K. Mittelstraß , I. Giegling , C. Lamina ,
H. Brenner5, C. Fehr4 , LP. Breitling5, E. Raum5,
D. Rothenbacher5, J. Gallinat6, Prokisch H9, A. Ruppert2,
AM. Hartmann1, HJ. Möller1, A. Gal7, Ch. Gieger3,
HE. Wichmann3, T. Illig3, G. Winterer8, N. Dahmen4
1
Division of Molecular and Clinical Neurobiology, Department
of Psychiatry, Ludwig-Maximilians-University, Nußbaumstr. 7,
80336 Munich, Germany
2
Genetics Research Centre GmbH, Nußbaumstr. 7, 80336
Munich, Germany
3
Helmholtz Zentrum Muenchen, German Research Center
for Environmental Health (GmbH), Institute of Epidemiology/
AGBIOGEN, Ingolstädter Landstr. 1, 85764, Neuherberg,
Germany
4
Department of Psychiatry, University of Mainz, Untere
Zahlbacher Strasse 8, 55131 Mainz, Germany
5
Division of Clinical Epidemiology and Aging Research, German
Cancer Research Center, 69115 Heidelberg, Germany
6
Department of Psychiatry, Charité University Medicine Berlin,
Campus Mitte, Berlin, Germany
7
Institute for Human Genetics, University of Hamburg Medical
Center Eppendorf, 22529 Hamburg, Germany
8
Department of Psychiatry, Heinrich Heine University, 40629
Düsseldorf, Germany
9
Helmholtz Zentrum Muenchen, German Research Center for
Environmental Health (GmbH), Institute of Human Genetics,
Ingolstädter Landstr. 1, 85764, Neuherberg, Germany
1,2#
3#
1
3
Nicotine dependence, which is partially heritable, is the
leading preventable cause of death and morbidity causing
an immense public health problem. Several recent studies
described an association of the nicotinic acetylcholine receptor
gene cluster on chromosome 15q24 with facets of smoking
behavior. Further studies provided strong evidence for an
association between SNPs within this cluster and lung cancer,
but they differ in their interpretation of their findings. Given the
well established association between smoking and lung cancer,
a plausible explanation is that this association is mediated by
smoking behavior. Here we deliver strong evidence that SNPs
(rs684513, rs637137, rs16969968, rs578776, rs1051730,
rs3743078, rs3813567) in the 15q24 region are associated
with nicotine dependence in three independent cohorts
comprising 5533 individuals. Remarkably, most investigated
SNPs showed association with nicotine dependence in all
cohorts including same allelic directionality and similar ORs
(Fixed effects inverse variance: p=7.47E-05; combined
OR(95%CI)=1.19[1.09,1.29] for rs1051730). Furthermore,
the associated SNPs showed the same allelic directionality
as SNPs or their proxies in the above mentioned studies
further supporting these findings. Interestingly, two risk alleles
were also associated with higher CHRNA5 gene expression
suggesting a functional relevance (rs684513 p=0.005;
rs637137 p=0.001). The expression findings provide evidence
for a functionality of these two SNPs. In summary, we report
associations between nicotine dependence and the nicotinic
acetylcholine receptor gene cluster on chromosome 15q24 in
three independent cohorts. These findings strongly suggest an
involvement of gene variants within this gene cluster in nicotine
dependence. Furthermore, we will discuss their implications for
schizophrenia and related intermediate phenotypes.
Biography
Since 1997 head of the Molecular and Clinical Neurobiology
at the Dept. of Psychiatry, University of Munich, Germany. The
major focus of this section is on the genetics of neuropsychiatric
diseases and behavioural phenotypes, especially on the
genetics of schizophrenia, cognition, addiction, aggression and
suicide. It follows a multidimensional translational approach
which involves recruitment and extensive phenotyping of
large samples, high throughput genotyping, and cellular
and animal models. Dan Rujescu has extensive experience in
implying intermediate phenotype approaches in the genetics of
complex traits. His group has extensively phenotyped ca. 3700
individuals for genetic studies. The section has postdocs, PhD
students and laboratory technicians with expertise in molecular
and cell biology techniques. Since 2005 he is a member of the
Managing Board of the Genetics Research Centre.
Dan Rujescu is involved in numerous scientific societies: since
2006/2008: Secretary/Head of the “Task Force on Genetics” of
the WFSBP; since 2006: Secretary of the Section “Suicidology”
of the Association of European Psychiatrists; since 2008: Chair
of the Section “Genetics” of the German Society of Biological
Psychiatry; since 2009: Chair of the Task Force „Genetics of
Suicide“ of the IASP“. Furthermore Dan Rujescu has numerous
experiences in the organisation of scientific congresses: 20002002: Co-Chair of the Organising Committee of the 7th
World Congress of Biological Psychiatry; 2004-2006: CoChair of the Local Organising Committee of the 13th AEP
Congress; 2006-2008: Co-Chair of the Local Organising
Committee of the 26th CINP Congress. Dan Rujescu received
the following awards: The NARSAD Independent Investigator
Award (William & Gloria Paul Family Foundation) in 2006, the
Kraepelin Research Award in 2007 and the Dr. Paul Janssen
Schizophrenia Research Award in 2008.
Major Psychoses and Substance Abuse
21
Abstracts and Biographies
Sunday 26th April 2009 Chairman: Dr Paul Fletcher, UK
10.30 – 12.00 Fintry Room
Parallel Session 3: Stimulants
Dr Isabelle Boileau, Canada
Amphetamine sensitization in man
Abstract
Sensitization of the mesolimbic dopamine system has
been implied in a wide range of psychiatric disorders
including addiction and psychosis. We used PET/[11C]
raclopride in humans to investigate whether repeated
exposure to drugs of abuse leads to increased dopamine
release, when challenged with amphetamine, drugassociated cues or stress. We find that repeated exposure
to amphetamine results in greater striatal [11C]raclopride
displacement in response to amphetamine, stress; and
drug-associated cues (placebo). Our results support
the view that repeated exposure to amphetamine leads
to long-lasting sensitization of the dopamine system in
humans.
22
Biography
I am a clinical research scientist working in the Positron
Emission Tomography Centre at the Centre for Addiction
and Mental Health in Toronto, Canada. I have a position
(since 2009) within the Schizophrenia and Addictions
programs where I am investigating, via PET imaging
techniques and psychopharmacology, the neurobiology
of behavior, mood and cognitive states associated with
schizophrenia drug-abuse and impulse control disorders.
I obtained my Ph.D. from McGill University, Montréal
Canada in 2006.
Collegium Internationale Neuro-Psychopharmacologicum
Sunday 26th April 2009 Chairman: Dr Paul Fletcher, UK
10.30 – 12.00 Fintry Room
Parallel Session 3: Stimulants
Dr Paul Fletcher, UK
Ketamine-induced psychoses
Abstract
Biography
Ketamine – a non-competitive NMDA antagonist –
produces a dissociative state with some features that are
redolent of the psychotic features found in schizophrenia.
Administration of ketamine to healthy volunteers has
produced data that are indirectly supportive of the NMDA
receptor hypofunction model of schizophrenia. However,
there is much work to be done in characterising the
dissociative and psychotic symptoms induced by ketamine
and in exploring the potential underlying cognitive
disruptions that may produce them.
I was awarded a Wellcome Trust Senior Research Fellowship
in Clinical Science in 2001 (renewed 2006) and hold the
Bernard Wolfe Professorship of Health Neuroscience at
Cambridge University.
Bernard Wolfe Professor of Health Neuroscience
Wellcome Trust Senior Research Fellow in Clinical Science
I trained in medicine, then psychiatry, in London and
began functional neuroimaging research at the MRC
Cyclotron Unit, Hammersmith Hospital and then the
Institute of Neurology. I study the brain basis for associative
learning and reward with a view to understanding the
symptoms of schizophrenia. I do this through functional
MRI and psychopharmacolgical experiments with healthy
participants and patients.
I will report data evaluating the extent to which ketamine
produces changes in the experience of agency – of being
the instigator of one’s actions. The sense of agency (SoA)
is thought to be disrupted in schizophrenia and there are
a number of experimental manipulations that enable us
to measure such changes objectively. I will briefly review
how disruptions in SoA might produce key symptoms
of schizophrenia and consider experimental evidence
that such disruptions do indeed exist. I will present the
results of some initial studies of the impact of ketamine
on measures of SoA in healthy subjects and consider the
extent to which these data provide further support for the
ketamine model of schizophrenia.
Major Psychoses and Substance Abuse
23
Abstracts and Biographies
Sunday 26th April 2009 Chairman: Dr Paul Fletcher, UK
10.30 – 12.00 Fintry Room
Parallel Session 3: Stimulants
Dr Graham Murray, UK
Cognition in Parkinson’s disease psychosis
Biography
After reading physics and philosophy at Oxford, Graham
Murray attended King’s College London School of
Medicine, where he graduated with distinction. He
trained in postgraduate clinical psychiatry and functional
neuroimaging in Cambridge University and studied
cognitive epidemiology in Cambridge and Oulu University
in Finland. He is interested in the psychopathology of
dopamine disturbance, and in explanatory relationships
between neurophysiology and mental states, especially
mental states relating to reward and motivation. He is
funded by a Medical Research Council Clinician Scientist
fellowship and NARSAD.
24
Collegium Internationale Neuro-Psychopharmacologicum
Sunday 26th April 2009 Chairman: Dr Paul Fletcher, UK
10.30 – 12.00 Fintry Room
Parallel Session 3: Stimulants
Prof. Nori Takei, Japan
Mechanisms underlying methamphetamine psychoses
Abstract
Methamphetamine is a powerfully addictive drug, and
the number of its abusers has been increasing worldwide.
Long-term methamphetamine abuse can produce various
psychiatric symptoms, including psychosis and aggression.
These psychiatric states are sometimes prolonged, in the
form of residual symptoms, and are easily exacerbated in
some long-term abusers by methamphetamine reuse or
by psychological stress.
In a series of our recent studies with positron emission
tomography (PET), we found that longer use of
methamphetamine cause greater reduction of dopamine
transporter density in the brain. The degree of psychiatric
symptoms in methamphetamine abusers were associated
with reduced dopamine transporter density mainly in
the orbitofrontal cortex and the dorsolateral prefrontal
cortex. In a separate study, we also found that protracted
abuse of methamphetamine reduces the density of the
serotonin transporter in the brain, which leads to elevated
aggression even in currently abstinent abusers. These
data are to be presented at the meeting.
Biography
Degree
1982 1994
1997
M.D., Graduated, Iwate Medical College, Japan
M.Sc. London School of Hygiene & Tropical
Medicine, University of London
Ph.D., Medicine, University of Tokyo
Postgraduate
1982 -1989 1989 -1991
1991 -1993
1993 -1995
1995 -1998
1998-2002
Appointments
Trainee, then Assistant, Dept of Neuropsychiatry,
Tokyo Women’s Medical College
Visiting Research Psychiatrist,
Institute of Psychiatry, London
Research Psychiatrist, Genetics Section
and Department of Psychological
Medicine, Institute of Psychiatry, London
Honorary Lecturer, Department of
Psychological Medicine, Institute of
Psychiatry, London
Senior Lecturer, Department of
Psychological Medicine, Institute of
Psychiatry, London
Honorary Senior Lecturer, Department of
Psychological Medicine, Institute of
Psychiatry, London
1998 -2000 Assistant Professor, Department of
Psychiatry & Neurology, Hamamatsu
University School of Medicine, Japan
2002- Visiting Professor, Department of Psychological
Medicine, Institute of Psychiatry, King’s College,
London
2000- Associate Professor, Department of Psychiatry &
Neurology, Hamamatsu University School of
Medicine, Japan
2007- Professor, Research Center for Child Mental
Development, Hamamatsu University School of
Medicine, Japan
2009- Professor, United Graduate School of Child
Development, Osaka University, Kanazawa
University and Hamamatsu University School
of Medicine
Publications (international peer-review journals: over 200
publications including the following)
1 Takei N., Sham P.C., O’Callaghan E., Murray R.M.:
Cities, winter birth, and schizophrenia. Lancet 340
(8818): 558-559, 1992.
2. Takei N., Sham P., O’Callaghan E., Murray G.K.,
Glover G., Murray R.M.: Prenatal exposure to
influenza and the development of schizophrenia: is
the effect confined to females? Am J Psychiatr
151 (1): 117-119, 1994.
3. Sekine Y., Ouchi Y., Takei N., Yoshikawa E.,
Nakamura K., Futatsubashi M., Okada H., Minabe Y.,
Suzuki K., Iwata Y., Tsuchiya K.J., Tsukada H.,
Iyo M., Mori N.: Brain Serotonin Transporter Density
and Aggression in Abstinent Methamphetamine
Abusers. Arch Gen Psychiar 63(1):90-100, 2006.
4. Sekine Y., Ouchi Y., Sugihara G., Takei N.,
Yoshikawa E., Nakamura K., Iwata Y., Tsuchiya K.J.,
Suda S., Suzuki K., Kawai M., Takebayashi K.,
Yamamoto S., Matsuzaki H., Ueki T., Mori N.,
Gold M.S., Cadet J.L.: Methamphetamine causes
microglial activation in the brains of human abusers.
J Neurosci May 28;28(22):5756-61, 2008.
5. Tsuchiya KJ, Matsumoto K, Miyachi T, Tsujii M,
Nakamura K, Takagai S, Kawai M, Yagi A, Iwaki K,
Suda S, Sugihara G, Iwata Y, Matsuzaki H, Sekine Y,
Suzuki K, Sugiyama T, Mori N, Takei N.: Paternal age
at birth and high-functioning autism spectrum
disorder in the offspring. Bri J Psychiar Oct;193(4):316 21, 2008.
Major Psychoses and Substance Abuse
25
Abstracts and Biographies
Sunday 26th April 2009 Chairman: Dr Paul Fletcher, UK
10.30 – 12.00 Fintry Room
Parallel Session 3: Stimulants
Dr Tomáš Páleničk, Czech Republic
From early to present use of psychedelic drugs such as LSD in research
and psychiatry
Abstract
Psychedelic drugs belong to daily life in almost every
culture around the world. Western civilization discovered
psychedelic substances after the synthesis of lysergic
acid diethylamide (LSD) in 1943 by the Swiss chemist
Albert Hofmann. Psychedelics were then used in scientific
quarters as well as by people experimenting with altered
states of consciousness - psychonauts. Psychedelics
began to be used as a means of achieving an intense
level of amusement among young people known as
recreational drug users. In scientific quarters psychedelics
mainly interested psychiatrists who used these substances
in treatment or in the study of psychiatric disorders. In
many cases these early experiments ignored all of the
ethical guidelines we respect today. On the other hand
psychotherapists attempted to use these substances as
a means of opening human sub-consciousness. Many
scientists who influenced psychedelic research of the human
psyche reached worldwide recognition, amongst them
were Aldous Huxley, Timothy Leary, John Cunningham
Lilly and Stanislav Grof. Between the 1960s and 1980s
there was a decline in psychedelic research, mainly due to
political reasons and the related criminalization of these
substances. Later on research into psychedelics became
the focus of interest of many psychiatrists once again.
Today these substances are studied intensively as models
of psychotic disorders, form a phenomenological point
of view, they are used to understand the neurobiological
correlation of human consciousness, cognitive functions,
and emotions etc. Some of these substances, e.g.
ayahuasca, ibogain, psilocybin or ketamine are also
used in the experimental treatment of addiction, cluster
headaches or pharmaco-resistant depression. Another
substance, entactogen MDMA, is used in the experimental
treatment of post-traumatic stress disorder (PTSD).
Biography
Tomáš Páleníček graduated from the 3rd Faculty of
Medicine, Charles University, in Prague in 2001. His
research activities started prior to him graduating; at this
time he focused his attention on drug addiction. After
completing his medical studies he continued on a PhD
at the same university working in the Prague Psychiatric
Centre. His thesis is entitled “The role of serotonergic
and dopaminergic neurotransmission in animal model of
schizophrenia” and he is expected to graduate in March
2009. Due to the fact that the modeling of psychosis in
animals as well as humans is associated with the research
of psychedelics (serotonergic and glutamatergic models
of psychoses), he has concentrated mainly on this topic
for the past four years. During his research he became the
principle investigator of two preclinical projects dealing
with psychedelic substances such as LSD, psilocybin,
mescaline, MDMA and more recently 2C-B and he is
also a co-investigator of projects on animal models of
psychosis. His latest research activities are concentrated
on quantitative EEG in these models. His clinical training
in psychiatry began in 2005 at the same institution. In
connection with clinical skills he is also trained in group
dynamic psychotherapy and in 2007 passed a training
course called “Stargate” allowing him to working with
altered states of consciousness. He has participated in
human psychedelic research since 2008 and is responsible
for the method which measures sensorimotor gating in
humans (prepulse inhibition of acoustic startle reaction)
in a ketamine model of psychosis.
This work has been supported by the project CNS MSMT
CR 1M0517 and MZ0PCP2005.
26
Collegium Internationale Neuro-Psychopharmacologicum
Sunday 26th April 2009 Chairman: Prof. Wolfgang Fleischhacker, Austria
12.00 – 13.15 Pentland Auditorium
Pfizer Satellite Symposium: The Links between Smoking and Psychiatric Disease: What can be done to help?
Prof. Georg Winterer, Germany
“An Overview of Smoking and Psychiatric Disease”
Dr Hans Rollema, Pfizer Groton, USA
“The Mechanisms of Nicotine Addiction and Approaches to Overcome it”
Prof. Henri-Jean Aubin, France
“Current Approaches to Smoking Cessation in Patients with Psychiatric Disease”
Prof. Torgny H. Svensson
“Future Approaches to Smoking Cessation in Patients with Psychiatric Disease”
This
Pfizer
sponsored
symposium, in line with the
theme for this year’s CINP
meeting, will discuss the links
between nicotine addiction
and psychiatric disease.
Within the symposium you will firstly see data on the
connection that exists between smoking and psychiatric
disease. Smoking can lead to psychiatric disease, and
patients with psychiatric disease are more likely to smoke.
You will then hear information on the CNS mechanisms of
nicotine addiction, including the role of the the neuronal
nicotinic receptors.
Patients with psychiatric disease, like all smokers, suffer
the burden of smoking related disease. This makes it
very important to help them stop smoking. Therefore
the symposium will go on to discuss the approaches that
can be used to help these patients stop smoking, and the
challenges that must be overcome. This will be discussed
in terms of current approaches as well as approaches that
may be considered in the future.
Major Psychoses and Substance Abuse
27
Abstracts and Biographies
Sunday 26th April 2009 Chairman: Prof. Anissa Abi-Dargham, USA
14.00 – 15.30 Pentland Auditorium
Parallel Session 4: Two faces of Dopamine
Prof. Anissa Abi-Dargham, USA
Dopamine alterations in comorbidity
Abstract
Dopamine (DA) plays a role in the pathophysiology of
schizophrenia and addiction. Imaging studies examining
effects of acute changes in dopamine levels on D2
radiotracer binding, using PET scanning with the D2/3
receptor radiotracer [11C]raclopride before and after
administration of 0.3 mg/kg iv D-amphetamine have
shown that DA transmission is predominantly blunted
in the ventral striatum (VST) in alcoholism and, to some
extent, in cocaine dependence. On the other hand,
in schizophrenia, DA transmission is increased in the
associative striatum (AST), and, more specifically, in the
precommissural caudate (preDCA). We are currently
conducting a study to examine dopamine transmission
in patients comorbid for schizophrenia and dependence.
To date we have 8 patients with schizophrenia and
dependence on alcohol, cocaine and cannabis, age: 28
± 7 y, gender: 6 males, 2 females, ethnicity: 3 H, 3 C,
and 2 AA. Data collection is on going but we will present
results from this initial sample. Displacement in the three
subdivisions of the striatum in the patients group is 10±
15 in VST, 7± 11 in AST and 10±8 in the sensorimotor
striatum (SMST). The magnitude of displacement in these
patients and the baseline D2 binding potential will be
compared to those in 9 healthy controls acquired to date,
age : 29 ± 6y, gender: 7 M, 2 F, ethnicity: 2 H, 4 C, 2 AA,
1As. Relationships to clinical syndromes will be assessed
and discussed at the meeting. Study funded by NIDA.
28
Biography
Anissa Abi-Dargham, MD, is a Professor of Clinical
Psychiatry and Radiology at Columbia University, New
York State Psychiatric Institute, and heads the Division of
Translational Imaging. Most of her career has focused
on the development of tools to image the neurochemical
alterations in the brains of patients with schizophrenia
and addictions. Her studies have contributed greatly to
the current understanding of the dopaminergic alterations
in these disorders as well as the interactions between
glutamate and dopamine. She has received funding from
NIMH, NIDA and NIAAA, as well as NARSAD, Lilly, BMS
and GSK. She has over 90 publications and is recognized
internationally as an expert in the area of Imaging and
Psychopharmacology.
Collegium Internationale Neuro-Psychopharmacologicum
Sunday 26th April 2009 Chairman: Prof. Anissa Abi-Dargham, USA
14.00 – 15.30 Pentland Auditorium
Parallel Session 4: Two faces of Dopamine
Dr Christoph Kellendonk, USA
Excess dopamine D2 receptors in the striatum affect cognition
and motivation in mice
Abstract
Increased activation of dopamine D2 receptors in the
striatum has been linked to the pathophysiology of
schizophrenia. In the mouse, selective over-expression
of D2 receptors in the striatum leads to alterations in
prefrontal-cortex dependent behaviors that resemble
some of the cognitive deficits observed in patients with
schizophrenia. Developmental over-expression of D2
receptors is sufficient to induce these deficits, because
switching off transgenic D2 receptors in adulthood does
not reverse the cognitive deficits.
Striatal D2 receptor over-expression also decreases
the motivation to work for food, but in contrast to the
cognitive impairment, the motivational deficit is rescued
by switching-off the excess D2 receptors.
Here, I will present the potential mechanisms that
may underlie the deficit in motivation and discuss how
alterations in reward processing could affect addiction
related behavior.
Biography
Christoph Kellendonk received his Ph.D. from the
University of Heidelberg in Germany. For his thesis he
studied the function of the glucocorticoid receptor gene in
the mouse using conditional mutagenesis. He then joined
the laboratory of Eric Kandel at Columbia University
where he became interested in generating mouse models
of schizophrenia endophenotypes. Dr. Kellendonk is
currently an assistant professor of Pharmacology in
Psychiatry at Columbia University.
Major Psychoses and Substance Abuse
29
Abstracts and Biographies
Sunday 26th April 2009 Chairman: Prof. Anissa Abi-Dargham, USA
14.00 – 15.30 Pentland Auditorium
Parallel Session 4: Two faces of Dopamine
Dr Eleanor Simpson, USA
Modelling endophenotypes for addiction and schizophrenia in COMT
over-expressing mice
Abstract
The rewarding effects of positive reinforcers, including
food, sex and drugs of abuse are thought to be mediated
by the mesolimbic dopamine system. COMT enzyme
activity regulates both cortical and subcortical dopamine
levels. In humans, the high enzyme activity allele (Val158)
has consistently been associated with poorer cognitive
performance. We have replicated this finding in transgenic
mice over-expressing COMT. Mice are specifically affected
in an operant task involving appetitive rewards. Recently,
the COMT Val158Met allele has also been shown to
influence the ability to experience rewards in human
subjects, a mechanism which may possibly contribute to
the development of affective or addictive disorders. We
therefore explore if the learning deficit we observe in
COMT overexpressing mice relates to a difference in the
animals response to reward.
30
Biography
Eleanor Simpson received her PhD in Genetics at the MRC
human Genetics Unit in Edinburgh. She then became
a HHMI Post doctoral fellow at Columbia University
where she began developing genetic mouse models of
schizophrenia endophenotypes. She is currently an Asst.
Prof. of Clinical Neurobiology in Psychiatry at Columbia
University and the New York State Psychiatric Institute.
Collegium Internationale Neuro-Psychopharmacologicum
Sunday 26th April 2009 Chairman: Prof. Anissa Abi-Dargham, USA
14.00 – 15.30 Pentland Auditorium
Parallel Session 4: Two faces of Dopamine
Prof. Anthony Grace, USA
Schizophrenia, stress, and drug abuse: common pathophysiological mechanisms
Abstract
For many years, schizophrenia has been considered to
be a disorder related to hyper-responsivity within the
dopamine system. However, the source of this hyperresponsivity is unclear. Using a developmental rat model,
we found that the ventral subiculum of the hippocampus
demonstrates an elevated level of activity compared to
controls. This is important because our research has
shown that the ventral subiculum controls a unique
aspect of dopamine neuron firing; i.e., the proportion of
dopamine neurons that are spontaneously firing. Our
work further showed that the amplitude of the phasic,
behaviorally relevant response of the dopamine system to
stimuli is dependent on the number of dopamine neurons
that can be phasically activated. Thus, the larger the
proportion of active neurons, the greater the amplitude
of the response. As a consequence, in the schizophrenia
model the ventral subicular hyperactivity leads to an
overabundance of active dopamine neurons, thereby
triggering abnormally large phasic dopamine responses
to stimuli. Both the increase in dopamine neuron activity
and the heightened behavioral response to amphetamine
in this model can be reset by inhibition of this abnormally
active ventral subiculum.
The increased dopamine system responsivity we
believe contributes to other disorders that exhibit a
hyper-responsivity of the dopamine system. Thus, with
repeated administration of amphetamine, an animal
will show a progressively greater behavioral response
to an amphetamine challenge after withdrawal. We
found that amphetamine sensitization is accompanied by
hyperactivity within the ventral subiculum and abnormally
high numbers of spontaneously active dopamine neurons.
As in the schizophrenia model, inactivation of the ventral
subiculum restores both the dopamine neuron firing and
the behavioral response to amphetamine back to control
levels. Stress has also been demonstrated to lead to
hyper-responsivity to amphetamine. Similar to repeated
amphetamine, exposure of a rat to restraint stress prior
to recording also increases dopamine neuron activity in a
manner that is also dependent on the ventral subiculum.
Therefore, factors that increase dopamine neuron
population activity, such as stress and amphetamine
sensitization, both act via the ventral subiculum, and both
are risk factors in schizophrenia. We propose that this is
due to a common disruption of ventral subicular control
of dopamine system responsivity.
Pharmacological
restoration of ventral subicular activity may therefore be
an effective therapeutic tool in reversing the psychosis of
schizophrenia.
Biography
Anthony A. Grace received his Ph.D. in Pharmacology
at Yale University. He is now Professor of Neuroscience,
Psychiatry, and Psychology at the University of Pittsburgh.
Dr. Grace’s research interests lie at the interface of
neurobiology and psychiatry. His laboratory combines
in vivo and in vitro electrophysiological recordings of
identified neurons with behavioral and neuroanatomical
techniques to study central dopaminergic systems, with
the ultimate goal of determining the neurobiological
correlates of mental disorders and the modes of action
of psychotherapeutic drugs. Ongoing studies into the
neurobiology of schizophrenia involve study of the
interaction of the prefrontal cortex and hippocampus with
subcortical dopamine systems, and examining the impact
of developmental disruption on limbic system function, as
a model for the pathophysiological changes underlying
schizophrenia in humans.
Major Psychoses and Substance Abuse
31
Abstracts and Biographies
Sunday 26th April 2009 Chairman: Prof. Euphrosyne Gouzoulis-Mayfrank, Germany
14.00 – 15.30 Sidlaw Room
Parallel Session 5: Hallucinogenic drugs and psychosis – psychopathology
and brain mechanisms
Prof. Franz X. Vollenweider, Switzerland
Spatiotemporal brain imaging of visual hallucinations induced by the 5-HT2A
agonist psilocybin in humans
Abstract
Franz X. Vollenweider, Michael Kometer
University Hospital of Psychiatry
Neuropsychopharmacology and Brain Imaging Unit
& Heffter Research Center
Lenggstrasse 31
CH-8032 Zurich, Switzerland.
Email: [email protected]
Background:
The preferential serotonin-2A agonist psilocybin is known
for its ability to produce a model psychosis including
visual illusions and hallucinations that mimics some of the
signs and symptoms of insipient schizophrenia. However
the spatiotemporal and pharmacological mechanisms of
visual disturbances and hallucinations in psychosis are
rarely understood.
Aims:
To further explore the neuronal correlates of visual
hallucinations the effect of psilocybin (215 µg/kg vs
placebo) on regional brain activation in normal subjects
was investigated using H2O-PET (n=12). Given that
some but not all schizophrenia patients show deficits in
visual object completion associated with alterations in the
N170 ERP component, the effect of psilocybin (115 µg/
and 215 µg/kg vs placebo) on object completion using
Kanizsa figures and EEG/ERP was employed in a second
study with normal subjects (n=17).
Results:
First, in the PET study, psilocybin administration in normals
resulted in a significant activation of the frontomedial
cortex and a deactivation of occipitoparietal regions
associated with the extent of visual hallucination. Second,
the spatiotemporal analysis of the effects of psilocybin on
visual processing using EEG-ERP technique revealed a
dose-dependent deactivation of visual areas (V2/LOC) at
the time range of the N170 component. Moreover, visual
hallucination correlated with the deactivation in LOC and
the ajacent parietal region.
32
Conclusion:
The present findings suggest that a disruption of
functional integrity of frontomedial and occipitopariatal
cortical regions contributes to visual hallucinations
in psilocybin states. Furthermore, the data indicated
that visual hallucinations occur with the impairment of
visual processing at the specific time range of the N170
component. Finally, the findings also strongly suggest
that the 5-HT2A receptor plays a pivotal role in visual
hallucination in this model and possibly also in psychiatric
disorders such as schizophrenia.
Biography
Dr. Franz X. Vollenweider is director of the
“Neuropsychopharmacology
and
Brain
Imaging
Research Unit” and the “Heffter Research Center” (HRC)
for Consciousness Research at the University Hospital of
Psychiatry, University of Zurich.
Dr. Vollenweider’s research interests encompass the
area of psychopathology, cognitive neuroscience,
and behavioural psychopharmacology. Current work
focuses on neural correlates of visual perception and
fundamental forms of sensory gating, and their relation
to cognitive functions and emotions. Multiple approaches
including pre-pulse inhibition of startle, event-related
potentials (EEG-ERP) and Positron-Emission-Tomography
PET in combination with psychological paradigms are
used for studying these functions in both normal subjects
and schizophrenia patients. Drug models of psychosis
including various hallucinogens are also employed to
elucidate the functional role of serotonin, glutamate, and
dopamine in the generation of hallucinations, cognitive
disturbances, and altered self-experiences in normal
subjects, and to further develop human models to explore
the effect of novel antipsychotics in humans.
Collegium Internationale Neuro-Psychopharmacologicum
Sunday 26th April 2009 Chairman: Prof. Euphrosyne Gouzoulis-Mayfrank, Germany
14.00 – 15.30 Sidlaw Room
Parallel Session 5: Hallucinogenic drugs and psychosis – psychopathology
and brain mechanisms
Prof. Bill Deakin, UK
Glutamate and the origin and progression of psychosis
Abstract
JFW Deakin, IB Chaudhry, J Hallak, N Hussein,
S Dursun
NPU, Department of Psychiatry, Manchester University,
M13 9PT
Reductions in grey matter volume are present in those
at risk of psychosis and further changes occur with the
onset of symptoms and continue during the early course
of the disorder. The cytoarchitectural and neurobiological
basis of these changes is far from clear. Evidence
suggests disinhibition of glutamate neurotransmission
may contribute to a subtle neurotoxic process. However,
there is recent interest in the possibility of an
inflammatory process. We have observed that one year
of add-on treatment in with the antibiotic minocycline
reduced negative symptoms. Whether this is due to
minocyline’s anti-inflammatroy or anti-glutamate effects
will be discussed.
Biography
Professor Bill Deakin is Professor of Psychiatry at
Manchester University and Director of the Neuroscience
and Psychiatry Unit (NPU), which he founded within the
Medical School. Professor Deakin spent nine years as a
Medical Research Council research fellow at the National
Institute for Medical Research at Mill Hill and the Clinical
Research Centre at Northwick Park. He attained the Chair
of Psychiatry in 1990. The main theme of his scientific
career has been to understand the role of 5HT in normal
behaviour and how disturbances lead to symptoms in
anxiety states and depression. More recently, he has
been interested in the role of glutamate in schizophrenia.
His group have developed magnetic resonance imaging
techniques to visualise the functioning of 5HT and
glutamate systems in living subjects. This is yielding new
insights into the role of neurotransmitters in fundamental
mechanisms of reward, punishment and psychosis. He
is active in realising the translational possibilities of
these techniques for the early detection of new drugs for
mental illness.
Major Psychoses and Substance Abuse
33
Abstracts and Biographies
Sunday 26th April 2009 Chairman: Prof. Euphrosyne Gouzoulis-Mayfrank, Germany
14.00 – 15.30 Sidlaw Room
Parallel Session 5: Hallucinogenic drugs and psychosis – psychopathology
and brain mechanisms
Dr Garry D. Honey, UK
Applying pharmacological models of psychosis to understand cognitive and physiological mechanisms associated with schizophrenia
Abstract
Pharmacological models of psychosis provide a
useful experimental tool with which to investigate the
neurobiological basis of the symptoms of schizophrenia.
In this presentation I will discuss the strengths and
weaknesses of this approach, and present data from
studies in which we have examined the cognitive and
phenomenological effects of two psychoactive agents,
ketamine and Δ-9-tetrahydrocannabinol (THC), which
elicit a broad range of the spectrum of symptoms of
schizophrenia. These data will be compared to that
acquired in patients, to determine the extent to which
these models reproduce important aspects of the illness.
We have also used neuroimaging as means to investigate
subjects’ susceptibility to these effects, and I will discuss
the use of inter-individual variability in cognitive and
related physiological processes to examine predisposition
towards psychotic experience. In extrapolating these
observations to schizophrenia, the aim of this work is
to enhance our understanding of the phenomenology
of the symptoms and the intrinsic biological mechanism
of psychosis.
34
Biography
Dr. Garry Honey is a cognitive neuroscientist who has
recently moved into the pharmaceutical industry, working
in Translational Medicine with Wyeth. He was formerly a
Principal Investigator at the Department of Psychiatry at
the University of Cambridge, supported by the MRC. His
primary research focus is on the neurobiological basis
of schizophrenia. To that end, he combines the use of
pharmacological neuroimaging (fMRI) with concurrent
administration of psychotogenic challenges, to provide a
model with which to further understand the physiological
mechanisms which give rise to cognitive dysfunction, and
predispose subjects to the symptoms of mental illness. He is
currently applying these techniques in the pharmaceutical
sector, in order to pursue pharmacological modelling of
psychosis as a translational approach to expedite drug
discovery in schizophrenia.
Collegium Internationale Neuro-Psychopharmacologicum
Sunday 26th April 2009 Chairman: Prof. Euphrosyne Gouzoulis-Mayfrank, Germany
14.00 – 15.30 Sidlaw Room
Parallel Session 5: Hallucinogenic drugs and psychosis – psychopathology
and brain mechanisms
Dr Joerg Daumann, Germany
Attention Processes and its Brain Mechanisms in the Human 5-HT2A Agonist and
NMDA Anta-gonist Model of Psychosis
Abstract
Deficits in attentional functions are counted among
the core cognitive symptoms in schizophrenic patients.
Pharmacologic challenges with hallucinogens have been
used as models for psychosis. We investigated the neural
correlates underlying alertness and spatial orienting of
attention in the human NMDA antagonist and 5-HT2A
agonist models of psychosis. Fourteen healthy volunteers
participated in a randomized double-blind, crossover
event-related functional resonance imaging study with
dimethyltryptamine (DMT) and S-ketamine. Administration
of DMT and S-ketamine led to different cortical activations
during performance of both tasks, although, both drugs
model overlapping psychopathological phenomena.
Pharmacological fMRI might be a profound tool to
distinguish different cortical activations triggered by the two
distinct types of drugs. This might deliver more insight into
potential differences and overlapping pathomechanisms
in schizophrenia.
Biography
From 1992 to 1998 Dr. Daumann studied psychology
at the University of Bonn. In 2002 he obtained his
Ph.D. from the University of Bielefeld in the field of
functional imaging. After working as a junior scientist
at the university hospitals of Aachen and Cologne he
became an assistant professor and, now, heads the
independent research area for Experimental Psychiatry
at the department of psychiatry and psychotherapy at
the University of Cologne. His scientific work is currently
focused on attentional dysfunctions in psychosis, deep
brain stimulation in obsessive-compulsive disorder, and
neurotoxicity of amphetamine derivatives.
Major Psychoses and Substance Abuse
35
Abstracts and Biographies
Sunday 26th April 2009 Chairman: Prof. Don Linszen, The Netherlands
14.00 – 15.30 Fintry Room
Parallel Session 6: Cannabis concerns: the experimental and sociological background
Prof. Roger Pertwee, UK
The endocannabinoid system
Abstract
The endocannabinoid system, which consists of
cannabinoid receptors and endogenous agonists for
these receptors (endocannabinoids), modulates the
severity of several disorders. One of these may be
schizophrenia as endocannabinoid release increases in
schizophrenia in a manner that may reduce unwanted
symptoms. Hence, drugs targeting the endocannabinoid
system, for example by augmenting the levels or actions
of released endocannabinoids, could have antipsychotic
effects. Schizophrenia is also associated with changes
in the density/binding properties of central cannabinoid
receptors. Although endocannabinoid release onto
certain cannabinoid receptor subpopulations may
be beneficial, activation of all central cannabinoid
receptors with an exogenously administered agonist
can trigger psychotic symptoms. One such agonist is
delta-9-tetrahydrocannabinol, the main psychoactive
constituent of cannabis. It is noteworthy, however, that
another cannabis constituent, cannabidiol, is showing
considerable promise as an antipsychotic.
36
Biography
Roger Pertwee has three degrees from the University of
Oxford: MA (in biochemistry), D.Phil. (in pharmacology)
and D.Sc (in physiological sciences). He is Professor of
Neuropharmacology at the University of Aberdeen,
Director of Pharmacology for GW Pharmaceuticals, cochairman of the International Union of Pharmacology
(IUPHAR) Subcommittee on Cannabinoid Receptors, a
co-ordinator of the British Pharmacological Society’s
Special Interest Group on Cannabinoids and visiting
Professor at the University of Hertfordshire. He has also
served as chairman of the International Association for
Cannabis as Medicine (2005-2007) and as President of
the International Cannabinoid Research Society (ICRS;
1997-1998 and 2007-2008) and is currently ICRS
International Secretary. He was the recipient of the 2002
Mechoulam Award “for his outstanding contributions
to cannabinoid research”. His research has focused
mainly on the pharmacology of cannabinoids. This he
began in 1968 at Oxford University and continued when
he moved to Aberdeen in 1974. His research has played
major roles in:
• the discovery of endocannabinoids and the
endocannabinoid system;
• the discovery that THCV is a plant cannabinoid
and a cannabinoid CB1 receptor antagonist;
• the pharmacological characterization of THCV
and other plant cannabinoids;
• the gathering of evidence supporting cannabinoids
for the management of multiple sclerosis;
• the discovery/characterization of novel synthetic
cannabinoids, e.g. the first water- soluble
cannabinoid (O-1057), the first CB1-selective
agonists (e.g. methanandamide) and a widely-used
CB2 antagonist (AM630);
• the discovery of a CB1 receptor allosteric site;
• the development of cannabinoid bioassays, some
widely used (e.g. the “ring test” and the mouse
vas deferens assay).
Collegium Internationale Neuro-Psychopharmacologicum
Sunday 26th April 2009 Chairman: Prof. Don Linszen, The Netherlands
14.00 – 15.30 Fintry Room
Parallel Session 6: Cannabis concerns: the experimental and sociological background
Dr David Potter, UK
Increasing Cannabis potency
Abstract
Until ten years ago, the most commonly used form of
cannabis in the UK was a product called ‘resin’. Since then,
the illicit market has become dominated by an intensively
grown form of herbal cannabis called ‘sinsemilla’ or
‘skunk’. Traditional cannabis resin is dominated by
three chemicals called tetrahydrocannabinol (THC),
cannabidiol (CBD) and cannabinol (CBN). THC is the
main psychoactive ingredient in cannabis, but CBD has
anti-psychotic properties and is thought to counteract the
effects of THC. Skunk is a very different product to resin
in that it is almost entirely devoid of CBD and has a much
higher average THC content. It is arguable therefore
that skunk is potentially more harmful than resin to those
individuals who are predisposed to cannabis-related
psychoses. Studies show that the average potency of
skunk in the UK, and the potential danger, is increasing.
Although relatively rare in the UK, new modern forms of
cannabis resin are available which are vastly more potent
than those previously available. These present a new
threat.
Biography
David Potter JP MIBiol CBiol FLS CMIOSH
David is Botanical Director for GW Pharmaceuticals
Ltd, a company propagating and testing cannabis for
medicinal use. In his eleven years with the company,
David has overseen the propagation of well over one
million cannabis plants. He is a Chartered Biologist
and is about to submit a PhD thesis in Pharmaceutical
Research at Kings College London. David has been
a magistrate for ten years, working in both adult and
youth courts in England. He has been an advisor on
cannabis issues to the police for many years and has
frequently acted as an expert witness.
As part of his PhD studies, he investigated the changing
potency of cannabis in England. The work was
published in the Journal of Forensic Sciences. In 2008
he presented this data to the ACMD to assist their
recommendations regarding the reclassification of
cannabis from Class C back to Class B.
In this presentation, the different forms of cannabis are
described and their changing pattern of use is discussed.
Major Psychoses and Substance Abuse
37
Abstracts and Biographies
Sunday 26th April 2009 Chairman: Prof. Don Linszen, The Netherlands
14.00 – 15.30 Fintry Room
Parallel Session 6: Cannabis concerns: the experimental and sociological background
Prof. Valerie Curran, UK
Differential effects on THC and CBD in “normal” cannabis smokers
Abstract
H Valerie Curran, UCL Clinical Psychopharmacology
Unit, Clinincla psychology, UCL, Gower Street, London
WC1E 6BT
Cannabis contains various cannabinoids, two of which
have almost opposing actions. Δ9- tetrahydrocannibinol
(THC) is psychotomimetic and cannabidiol (CBD) has
antipsychotic effects. We recently examined THC and
CBD in hair samples of 140 individuals. Three clear
groups emerged ‘THC only’, ‘THC and CBD’ and those
without cannabis in hair. Our results show higher levels of
unusual experiences, an analogue of hallucinations and
delusions, in individuals who had evidence of only THC in
their hair compared to those with both THC and CBD, or
no cannabis. There were also greater levels of delusions
in the THC only group. In a naturalistic study with 140
cannabis users and 144 non-using controls, acutely
smoked cannabis reliably induced psychotomimetic effects
which were significantly more marked in those higher in
psychosis-proneness. I shall present preliminary data
from another, ongoing naturalistic study examining the
acute effects of smoked cannabis which directly assessed
its CBD and THC content as well as biological markers
of these cannabinoids. Together, this research provides
evidence of the divergent properties of cannabinoids
and has implications for research into the link between
cannabis use, psychosis and dependence.
38
Biography
H Valerie Curran is Professor of Psychopharmacology
and Director of the Clinical Psychopharmacology Unit at
University College London. She is also Research Lead
for Camden & Islington’s NHS Substance Abuse Services.
Her current research related to psychosis-like symptoms
focuses on:
• differentiating the actions of different cannabinoids
on schizotypal symptoms, cognition and addiction related processes;
• exploring pharmacological models of psychotic
symptoms using ketamine and cannabinoids in
both challenge studies (acute administration to
healthy volunteers) and natural populations of
chronic users of these substances.
Collegium Internationale Neuro-Psychopharmacologicum
Sunday 26th April 2009 Chairman: Prof. Don Linszen, The Netherlands
14.00 – 15.30 Fintry Room
Parallel Session 6: Cannabis concerns: the experimental and sociological background
Dr Paul Morrison, UK
Acute effects of Intravenous THC
Abstract
The drug delta-9-tetrahydrocannabinol (THC), the main
ingredient in cannabis, can elicit psychotic symptoms in
otherwise healthy people. THC can induce schizophrenialike positive symptoms (ideas of reference, delusional
misrepresentation, loss of ego boundaries), negative
symptoms (reduced drive and sociability) and workingmemory deficits.
Biography
Paul Morrison studied medicine and psychiatry in
Glasgow and is currently a researcher at the Institute of
Psychiatry King’s College. At present he is investigating
the biochemical correlates of THC psychoses using SPET
neurochemical imaging.
THC acts at the CB1 receptor, where the endogenous
transmitter is a class of lipid molecule, typified by
2-arachodonoylglycerol (2-AG). In normal physiology
2-AG is released from the dendritic spines of principal
neurons (pyramidal cells, purkinje neurons, mediumspiny neurons, midbrain dopamine-containing neurons),
endowing these neurons with an ability to ‘switch-off’ their
excitatory and inhibitory inputs (retrograde transmission).
Beyond CB1, the pro-psychotic mechanisms of THC,
in terms of information-processing, remain unknown.
Here we speculate on candidate mechanisms. One
unanticipated ‘by-product’ of this endeavour, is that
the pro- and anti-psychotic mechanisms of classical
dopamine drugs become clearer. It appears that a range
of molecules (including dopaminergics and cannabinoids)
with the shared property that they impact on learning and
memory at cortico-striatal connections have either pro- or
antipsychotic effects.
Major Psychoses and Substance Abuse
39
Abstracts and Biographies
Sunday 26th April 2009 Chairman: Prof. Don Linszen, The Netherlands
14.00 – 15.30 Fintry Room
Parallel Session 6: Cannabis concerns: the experimental and sociological background
Dr Judith Allardyce, The Netherlands
Epidemiological Studies of Cannabis and Psychosis
Abstract
Randomised experimental studies have shown that exposure
to tetrahydrocannabinol (THC), the main psychotropic
component of cannabis, causes acute psychotic states to
which individuals with pre-existing liability to psychosis
are more susceptible than well controls. Systematic
reviews of prospective studies suggest that cannabis use is
associated with increased risk for psychotic disorder and
symptoms (OR around 1.5 to 2). Although it is difficult to
establish causality on the basis of epidemiological data,
the acute psychotic states induced by THC provide an
important model of psychotic symptoms. Several studies
suggest that cannabis may interact with genetic risk to
increase risk for psychotic disorders, including interaction
with variation in the gene encoding for COMT. Work will
be presented showing the complexity of this type of work
on gene-environment interactions.
40
Biography
Judith Allardyce, MPH, PhD ,MRCPsych: carried out her
psychiatric training in Newcastle-Upon-Tyne, England
before formally training in epidemiology in Glasgow,
Scotland. She worked as a consultant psychiatrist in
South Glasgow for many years and has held academic
positions in the Universities of Newcastle & Glasgow; she
has carried out epidemiology studies of severe mental
disorder s (especially psychosis)and is now working on
a project, examining the joint genetic & environmental
influences for the onset of psychosis, at the University of
Maastricht, The Netherlands.
Collegium Internationale Neuro-Psychopharmacologicum
Sunday 26th April 2009 Chairman: Prof. Robin Murray, UK
16.00 – 17.30 Pentland Auditorium
Parallel Session 7: Cannabis use and the presentation and outcome of psychosis
Prof. Philip McGuire, UK
A functional MRI study of the effects of cannabis
Abstract
Philip McGuire, Jose Crippa, Rocio Martin-Santos, Sagnik
Bhattacharyya, Stephan Borgwardt, Poalo Fusar-Poli, Paul
Allen, Toby Winton-Brown, Colin O’Carroll, Antonio
Zuardi, Marc Seal, Zerrin Atakan.
Section of Neuroimaging, Institute of Psychiatry, London
Background:
Cannabis use can induce psychotic symptoms and
anxiety and can alter cognitive and emotional processing.
We used functional neuroimaging to investigate the
neurocognitive basis of these effects, using experimental
tasks that engage processes known to be modulated by
cannabis use.
Methods:
Subjects were 15 healthy males who were not regular
cannabis users. Each subject was studied on 3 occasions,
and was given either THC, CBD or placebo 1 hour prior
to scanning, in a double-blind design. The order of drug
administration was randomised and there was 1 month
between each scanning session. During each session,
images were acquired on a 1.5T GE camera while subjects
performed a verbal paired associates memory task, a
Go/ No Go task, visual processing of anxious faces and
listening to speech. The modulatory effects of THC and
CBD relative to placebo were examined by comparing
activation during each task.
Conclusions:
The distinct symptomatic and cognitive effects of cannabis
can be related to the influence of THC and CBD on
specific brain regions.
Biography
Phillip McGuire is Professor of Psychiatry & Cognitive
Neuroscience at the Institute of Psychiatry & GKT School
of Medicine, London. He is Director of OASIS (Outreach
& Support in South London) and the Voices Clinic, South
London & Maudsley NHS Trust. He studied physiology
and medicine at the University of Edinburgh, then was a
research fellow in neuroanatomy at Yale University. After
training in psychiatry at the Maudsley hospital, he was a
Wellcome Training Research Fellow at the MRC PET Unit,
Hammersmith Hospital, and then a Senior Lecturer at the
Institute of Psychiatry in London. His research has mainly
focused on the neurocognitive basis of psychosis.
Results:
During verbal learning THC attenuated the response in the
medial temporal cortex compared to placebo. The acute
induction of psychotic symptoms by THC was correlatd with
its effects on striatal activation during verbal recognition.
During the go-no go task, THC attenuated activation in
the right inferior frontal cortex. THC and CBD both altered
activation in the auditory cortex during speech processing,
but in opposite directions. CBD attenuated activation in
the amygdala in response to fearful faces and this effect
was correlated with its effect on skin conductance.
Major Psychoses and Substance Abuse
41
Abstracts and Biographies
Sunday 26th April 2009 Chairman: Prof. Robin Murray, UK
16.00 – 17.30 Pentland Auditorium
Parallel Session 7: Cannabis use and the presentation and outcome of psychosis
Prof. Don Linszen, The Netherlands
Clinical studies of cannabis use
Abstract
Schizophrenia and related psychotic disorders are severe
mental disorders with a prevalence of about 1%. Most
patients with a characteristic onset in young adulthood
suffer from multiple psychotic episodes with increasing
impairment. Genetic and environmental factors play
an important etiological role. The rate of substance use
in schizophrenia is high: recent abuse for community
samples is estimated to range from 20-40% with cannabis
as preferred drug (Mueser et.al., 1992). This rates are
higher than those for the general population (Regier
et.al., 1990). Patients with schizophrenia and substance
abuse have been found at risk for serious complications,
including suicide, poor compliance with antipsychotic
medication, more admissions and violence. Recently
cannabis use has been found to be an independent risk
factor for the onset of psychosis and schizophrenia (Moore,
2007). Long-term follow-up studies have demonstrated,
that only a small minority of patients experience a
single psychotic episode; most patients suffer from
multiple psychotic episodes with varying residual and
negative symptoms and often increasing impairment.
The unfavourable long-term course of schizophrenia
and related psychotic disorders takes place in the early
phase of the disorders, which may be defined as a critical
period. Male gender, insidious and early age of onset,
long duration of untreated psychosis, low education and
absence of affective symptoms have been found to be
unmalleable risk factors for poor outcome. Cannabis use
and lack of compliance turned out to be malleable risk
factors for poor outcome. In a twelve month Dutch followup study with young first-episode patients cannabis use
was a significant risk factor for relapse (Linszen et al.,
1994). Cannabis use, abuse and dependence is frequently
observed in adolescent and young adult patients with
recent onset schizophrenia. In a review on 32 studies,
Mueser et al., (1992) showed that life-time prevalence
rates for cannabis abuse or dependence in patients with
schizophrenia ranged from 12-31%. More recent studies
have shown even higher rates of cannabis use problems
42
in patients with schizophrenia ranging from 30-50%
(Cuffel, 1993; Soyka et al., 1996; Fowler et al., 1998).
However, a number of clinical studies have shown that
cannabis use and cannabis use disorders are associated
with more positive symptoms, higher re-hospitalisation
rates and lower treatment compliance (Negrete et al.,
1986; Cleghorn et al., 1991). Results after the five year
Dutch intervention study in first episode psychoses and
schizophrenia (n=189) showed a 49 % relapse rate or
continuing psychosis. Main outcome predictors turned
out to be cannabis abuse (OR 9.34; 4.02-21.72),
lack of insight (OR 4.80; 1.41-12.26) and noncompliance (OR 5.06 ; CI 1.85-10.28) during the first six
months of the intervention with cannabis abuse predicting
low compliance.
Biography
Dr. Don Linszen, MD PhD is professor of Psychiatry at the
Academic Medical Center of the University of Amsterdam
(AMC-UvA) and director of the Adolescent Clinic of the
AMC-UvA in Amsterdam. His research interests include
the phenomenology of psychoses, schizophrenia and high
risk states of psychoses, the etiology and pathogenesis
of psychoses and schizophrenia, co-morbid cannabis
use and early recognition and pharmacotherapeutical
and psychosocial intervention in psychoses and
schizophrenia.
Linszen was member of the Amsterdam site of the steering
group of the “European Prediction of Psychosis Study
(EPOS).
At present he chairs the Dutch Health Care Fund sponsored
“Genetic Risk and Outcome of Psychosis (GROUP) study”
with as participants prof. R. Kahn (Univ Utrecht; prof.
J. van Os, Univ Maastricht ; prof. D. Wiersma, Univ.
Groningen). He is on the editorial board of the Journal of
Early Intervention in Psychiatry. With Jean Addington he
will organize the 7th congress of the International Early
Psychosis Association in Amsterdam in 2010.
Collegium Internationale Neuro-Psychopharmacologicum
Sunday 26th April 2009 Chairman: Prof. Robin Murray, UK
16.00 – 17.30 Pentland Auditorium
Parallel Session 7: Cannabis use and the presentation and outcome of psychosis
Dr Marta di Forti, UK
Skunk and Psychosis in South East London
Abstract
Marta Di Forti, Craig Morgan, Valeria Mondelli, Laura
Gittens,Rowena Handley,
Nilay Hepgul, Sonija Luzi,Tiago Marques, Monica Aas,
Sarah Masson,Corinne Prescott, Manuela Russo, Poonam
Sood, Ben Wiffen, Pietro Papili, Paola Dazzan, Carmine
Pariante, Kathy Aitchison, John Powell, Robin Murray.
Background:
Epidemiological studies have reported that the increased
risk of developing psychosis in cannabis users is dose
related. In addition, experimental research has shown
that the active constituent of cannabis responsible for
its psychotogenic effect is Delta-9-Tetrahydrocannabinol
(THC) (Murray et al, 2007). Recent evidence has suggested
an increased in potency (% TCH) in the cannabis seized in
the UK (Potter et al, 2007).
Hypothesis:
We predicted that first episode psychosis patients are
more likely to use higher potency cannabis and more
frequently than controls.
Methods:
We collected information concerning socio-demographic,
clinical characteristics and cannabis use (age at first use,
frequency, length of use, type of cannabis used) from a
sample of 280 first-episode psychosis patients and 174
matched healthy volunteers. All were recruited as part
of the Genetic and Psychosis (GAP) study which studied
all patients who presented to the South London and
Maudsley Trust.
preferentially used Skunk/Sinsemilla compared to 27.7%
of Controls. Only 13.2% of 1st Episode psychosis Patients
chose to use Resin/Hash compared to 76.3% of controls.
The concentration of TCH in these in South East London,
ranges between 8.5 and 14 % (Potter et al, 2007). Controls
(47%) were more likely to use Hash (Resin) whose average
TCH concentration is 3.4% (Potter et al, 2007).
Conclusions: Patients with first episode psychosis have
smoked higher potency cannabis, for longer and with
greater frequency, than healthy controls.
Biography
Marta Di Forti is a clinical academic, lecturer grade, of
the Department of Psychological Medicine, Institute of
Psychiatry, and London, where she is the co-ordinator of
the first-episode psychosis Genetics and Psychosis (GAP)
study. She is involved in research aimed at improving
the understanding of psychotic disorders. Her current PhD
focuses on the interaction between psychosis susceptibility
genes and known environmental risks factors, in the
aetiology of schizophrenia. Her main area of interest
concerns the role of cannabis in the onset and course
of Schizophrenia. She also works as an Adult-Old Age
Psychiatrist on one of the Maudsley Hospital Units, where
people with severe psychiatric illnesses and Dementia
come for in-patient treatment.
Results:
There was no significant difference in the life-time
prevalence of cannabis use or age at first use between
cases and controls. However, cases were more likely to be
regular users (p=0.05), to be current users (p=0.04) and
to have smoked cannabis for longer (p=0.01). Among
cannabis users, 86.8% of 1st Episode Psychosis Patients
Major Psychoses and Substance Abuse
43
Abstracts and Biographies
Sunday 26th April 2009 Chairman: Prof. Robin Murray, UK
16.00 – 17.30 Pentland Auditorium
Parallel Session 7: Cannabis use and the presentation and outcome of psychosis
Dr Cathy Fernandes, UK
Modelling the effects of cannabis in adolescent mice
Abstract
Cannabis use, especially during adolescence, confers
an increased risk of developing schizophrenia and
related disorders. While human studies are valuable in
identifying behavioural and genetic associations with
cannabis use, it is more difficult to assess the underlying
pathophysiological processes. Animal models are ideal
for this, since it is possible to combine exposure to the
main components of cannabis with specific developmental
periods. I will discuss the research using animal models
to investigate the behavioural effects of cannabis during
key stages of development and to determine the degree
to which vulnerability to the harmful effects of cannabis is
genetically influenced.
44
Biography
Cathy Fernandes is an RCUK Fellow with over 10 years
experience in integrative biology using animal models of
behaviour and gene expression profiling, with a particular
interest in modelling gene-environment interactions of
relevance to psychiatric disorders. She originally trained
as a psychopharmacologist at Guy’s Hospital, followed
by postdoctoral positions in molecular pharmacology at
the Royal Free & University College Medical School and
in behaviour genetics the Institute of Psychiatry, London.
Cathy recently completed a Marie Curie Fellowship at the
Rudolf Magnus Institute of Neuroscience in the Netherlands
and returned to the Institute of Psychiatry as an RCUK
Fellow in 2007. Currently, she is leading a research
project using animal models to determine why cannabis
use in adolescence is a risk factor for schizophrenia.
Cathy’s research includes work on animal models of
anxiety, depression and psychosis, factors influencing
the harmful effects of drug use, molecular mechanisms
of depression and antidepressant drug action and the
functional genomics of behaviour.
Collegium Internationale Neuro-Psychopharmacologicum
Sunday 26th April 2009 Chairman: Prof. Robin Murray, UK
16.00 – 17.30 Pentland Auditorium
Parallel Session 7: Cannabis use and the presentation and outcome of psychosis
Dr Wiepke Cahn, The Netherlands
Cannabis use and progression of brain changes
Abstract
The effects of cannabis on brain changes in
schizophrenia
René S. Kahn, MD., PhD. UMC Utrecht, The Netherlands
Objective: Cerebral gray matter volume reductions have
been found to progress over time in schizophrenia, with
larger decreases related to poorer outcome, which has
also been associated with cannabis use in schizophrenia
patients. Progressive gray matter changes in patients who
use cannabis may be more extensive than in those who
do not. Method: Patients with recent-onset schizophrenia
(N=51) and matched healthy subjects (N=31) were
included. For all subjects, magnetic resonance imaging
scans were obtained at inclusion (T0) and at 5-year followup (T5). Nineteen patients used cannabis but no other
illicit drugs; 32 patients did not use any drugs during the
5-year follow-up. At T5, clinical outcome was measured.
Cumulative amount of antipsychotic medication during
the interval was calculated. At T0 and T5, total brain, gray
and white matter, and lateral and third ventricle volumes
were measured. Univariate analysis of covariance and
pairwise comparisons were performed.
Result: Schizophrenia patients showed a larger gray
matter volume decrease over time than healthy subjects.
They also showed larger increases in lateral and third
ventricle volumes than healthy subjects and patients who
did not use cannabis during follow-up. This decrement
was significantly more pronounced in the patients who
continued to use cannabis. These differences could not be
attributed to outcome or baseline characteristics.
Conclusions: First-episode schizophrenia patients who
use cannabis show a more pronounced brain volume
reduction over a 5-year follow-up than patients with
schizophrenia who do not use cannabis. These results may
help explain some of the detrimental effects of cannabis
use in schizophrenia. (Am J Psychiatry Rais et al.; AiA:1–
7) Although the neurobiological basis of schizophrenia
is not yet fully understood (1), cross-sectional magnetic
resonance imaging (MRI) studies in patients with
schizophrenia have shown overall decreases in cortical
gray and white matter volume and in smaller brain
structures such as the amygdala-hippocampus complex,
as well as volume increases in the lateral ventricles (2, 3).
Moreover, the gray matter volume decrease and ventricular
increase appear to progress over time with most (4–12),
but not all (13), studies reporting the largest brain volume
decreasesin patients with the poorest outcome. Of interest,
poor clinical and functional outcome in schizophrenia has
been consistently associated with cannabis use. Cannabis
(ab)use occurs in 28%–50% of patients with schizophrenia
(14, 15), with those using cannabis having more positive
(16–20) (but not negative [16, 18, 20–22]) symptoms,
an earlier disease onset (23), and an increased number
of psychotic relapses or exacerbations (18, 24, 25)
compared to nonusing patients. Thus, if brain volume
changes over time are most prominent in the patients
with a poor outcome, and poor outcome is associated
with cannabis use, one would expect cannabis use to be
associated with excessive decreases in brain volumes.
However, no longitudinal studies examining the effect of
cannabis use on brain changes in schizophrenia have
been conducted to date. In a cross-sectional study, we
found that brain volumes in cannabisusing patients with
recent-onset schizophrenia did not differ from those of
cannabis-naive patients (26). This is consistent with the
results of previous cross-sectional brain imaging studies
comparing healthy subjects who use cannabis with those
who do not (for a review, see reference 27). Brain volume
changes over time, however, may prove to be more
sensitive in detecting the effect of cannabis on the brains
of schizophrenia patients. Indeed, cross-sectional MRI
studies have failed to predict outcome over time (28),
whereas longitudinal MRI studies show that an excessive
decrease in gray matter volume during the early course of
the illness is associated with poorer functioning 2 (6) and
5 (29) years later. Therefore, we hypothesized that in view
of the deleterious effects of cannabis on clinical outcome
and the reported relationship between outcome and brain
volume changes over time, cannabis-using patients with
schizophrenia would show larger brain volume decreases
over 5 years compared to nonusing patients and healthy
comparison subjects.
Major Psychoses and Substance Abuse
Continued...
45
Abstracts and Biographies
...Continued
Biography
Current Post
Chief Psychiatrist Schizophrenia Program, University
Medical Center Utrecht.
Assistant Professor Rudolf Magnus Institute of
neurosciences, Utrecht, The Netherlands
Previous Posts
1996-2000 Consultant psychiatrist Schizophrenia Unit
1995-1996 Registrar in Psychiatry at the UMCUtrecht.
1991-1995 Senior House Officer and Registrar in
Psychiatry at the United Medical and Dental School of
Guy’s and St. Thomas’ Hospitals, London, UK
Activities
Dr. Wiepke Cahn is the chief psychiatrist of the psychosis
and schizophrenia program, at the University Medical
Center Utrecht and an assistant professor at the
Rudolf Magnus Institute of neurosciences, Utrecht, The
Netherlands. Her main activity and interest is to unravel the
underlying neurobiological mechanisms of schizophrenia
through neuroimaging and genetic research. She has set
up and is involved in various national and international
multicenter research projects and is currently supervising
10 PhD students. Dr. Cahn is an editor of ‘Tijdschrift voor
Psychiatrie’ and is author of 50 papers and bookchapters.
Her non-research-based activities consist of treating (firstepisode) patients with schizophrenia and trying to prevent
the occurrence of psychoses in high risk patients.
46
Collegium Internationale Neuro-Psychopharmacologicum
Sunday 26th April 2009 Chairman: Prof. Torgny H. Svensson, Sweden
16.00 – 17.30 Sidlaw Room
Parallel Session 8: Clozapine and comorbid substance abuse in schizophrenia:
Mode of action and novel leads
Prof. Torgny H. Svensson, Sweden
Significance of alpha2 adrenoceptor blockade and NET inhibition for antipsychotic drug effects
Abstract
The dopamine (DA) hypothesis of schizophrenia posits a
hyperactive or hyper-reactive subcortical DA projection to
striatal areas of the brain, with bearing on positive symptoms,
concomitant with a functionally impaired prefrontal DA
projection, with bearing on cognitive deficits, e.g. of working
memory, as well as negative symptoms. Rodent studies
support the notion that atypical, but not typical, antipsychotic
drugs (APDs) increase DA output in the prefrontal cortex
(PFC), e.g. via 5-HT2A receptor blockade - and, in the
case of clozapine, alpha2 adrenoceptor antagonism.
Moreover, we have recently found that also inhibition
of the norepinephrine transporter (NET) may increase
the capability of both typical and atypical APDs such as
olanzapine to enhance the availability of DA in the PFC and
to potentiate their antipsychotic-like effect. By augmenting
the efficacy of typical and atypical APDs (with the exception
of clozapine) adjunctive alpha2 adrenoceptor blockage or
NET inhibition may thus, in principle, reduce the D2 receptor
occupancy required for clinical effects in schizophrenia,
potentially allowing for a reduction of both extrapyramidal
side effects and cognitive and motivational impairment as
well as weight gain. As selective NET inhibition also exerts
an antidepressant effect, an enhanced therapeutic effect
may also be expected in the treatment of bipolar depression.
The glutamate hypothesis of schizophrenia implicates
dysfunctional NMDA receptors, e.g. in the PFC. In line with
animal studies supporting this hypothesis, NMDA receptor
antagonists are known to exacerbate psychotic symptoms
and cognitive impairment in schizophrenic patients as well
as to induce similar symptoms in healthy volunteers. Atypical
APDs share a common property of augmenting NMDAevoked responses in pyramidal cells of the PFC, implying
facilitation of NMDA receptor-mediated transmission and
enhancement of their clinical effect on cognitive and negative
symptoms. In analogy with atypical APDs, the highly selective
NET inhibitor reboxetine also causes a moderate facilitation
of prefrontal NMDA receptor-mediated transmission and, in
addition, substantially enhances the effects of both typical
and atypical APDs in this regard. Consequently, an APD with
concomitant NET inhibitory activity, such as quetiapine, that
produces an active metabolite, norquetiapine, which is a
potent NET inhibitor in the primate brain, may be expected
to generate an improved effect in schizophrenia, particularly
on negative, cognitive and depressive symptoms, as well in
bipolar depression.
Biography
Dr. Svensson, M.D., is Professor of Pharmacology and a
member of the Nobel Assembly at the Karolinska Institutet
in Stockholm, Sweden. He received his Ph.D. degree from
the Medical Faculty, University of Gothenburg, Sweden,
under the tuition of Arvid Carlsson and subsequently spent
several years in the US, working both in New Haven, Conn.,
at Yale University Medical School, Depts. of Pharmacology
and Psychiatry, and subsequently, in the eighties, at
The Salk Institute, La Jolla, CA. He was appointed full
professor at the Karolinska Institutet in 1983 and has also
served as Chairman of the Department of Pharmacology.
Dr Svensson is the author of approximately 300 scientific
publications, among them seminal papers in Science
and Neuron as well as several patent applications, and
has been an invited speaker at innumerous international
meetings. He has served as scientific advisor to several
academic research institutions and drug companies and
has received numerous awards and honors, among them
the European College of Neuropsychopharmacology Lilly
Neuroscience, Basic Science Award in 2000. In 1997, he
founded Independent Pharmaceutica, a company aimed at
providing novel pharmacologic solutions for the treatment
of nicotine addiction. Dr. Svensson served as President of
the Scandinavian College of Neuro-Psychopharmacology
(SCNP) 2001–2005, and as President of the Collegium
Internationale Neuro-Psychopharmacologicum (CINP)
2006–2008. His major scientific contributions concern
the regulation and function of brain monoamine systems,
the mode of action of antidepressant and antipsychotic
drugs and various augmentation strategies, as well as
the neurobiological basis of nicotine dependence and its
treatment.
Major Psychoses and Substance Abuse
47
Abstracts and Biographies
Sunday 26th April 2009 Chairman: Prof. Torgny H. Svensson, Sweden
16.00 – 17.30 Sidlaw Room
Parallel Session 8: Clozapine and comorbid substance abuse in schizophrenia:
Mode of action and novel leads
Dr Svante Nyberg, Sweden
A translational perspective on quetiapine - clinical utility
Abstract
AstraZeneca R&D, Södertälje, Sweden
Quetiapine is approved for treating schizophrenia, bipolar
mania, and bipolar depression and also demonstrates
efficacy in major depressive disorder and generalized
anxiety disorder. Converging evidence from preclinical
and positron emission tomography (PET) studies may
explain the modes of action of quetiapine in mood and
anxiety disorders.
Quetiapine’s moderate D2 and high 5-HT2A receptor
occupancy has been well characterized. Recently, the
major active metabolite of quetiapine - norquetiapine
- has been shown to potently inhibit norepinephrine
transporter reuptake and to display moderate 5-HT2C
receptor antagonism and 5-HT1A partial agonism, which
are potential mediators of antidepressant and anxiolytic
effects. Taken together, the pharmacologic properties
of quetiapine have not been described for any other
psychotropic drug.
Biography
Following his medical studies in Umeå, Sweden,
Dr. Nyberg completed his residency in psychiatry at
Huddinge Hospital in 1989. He then moved to the position
of senior consultant at the department of psychiatry at
the Karolinska Hospital, where he started and led a large
outpatient unit for patients with schizophrenia. In parallel,
he worked with positron emission tomography (PET) studies
on antipsychotic drug action and presented his thesis in
1995 at the Karolinska Institutet. His continued imaging
work has resulted in several high-impact publications. Prior
to joining AstraZeneca, Dr. Nyberg was a section head
at the department of psychiatry, Huddinge Hospital, and
chaired the psychiatry group of the Regional Formulary
(Drug Committee), Stockholm, Sweden.
Dr. Nyberg joined AstraZeneca in 2004 and has
had several roles within Neuroscience Early Clinical
Development, building on his comprehensive psychiatry,
psychopharmacology, and PET imaging experience.
In particular, he is the leader of the AstraZeneca PET
working group, in close collaboration with the Karolinska
Institute, which has delivered PET studies and data serving
several projects in the Neuroscience portfolio. He was the
Director of Neuroscience Discovery Medicine from 2006
to 2008, accountable for all clinical translational science
in the Neuroscience portfolio of analgesia, neurology,
and psychiatry projects. Dr. Nyberg has now joined the
Seroquel team as the leader of the Seroquel Science
Strategy Team.
Reference:
Jensen NH, et al.
2008;33:2303-2312.
Neuropsychopharmacology.
48
Collegium Internationale Neuro-Psychopharmacologicum
Sunday 26th April 2009 Chairman: Prof. Torgny H. Svensson, Sweden
16.00 – 17.30 Sidlaw Room
Parallel Session 8: Clozapine and comorbid substance abuse in schizophrenia:
Mode of action and novel leads
Prof. Alan I. Green, USA
A Translational Perspective on Clozapine: Clinical Utility
Abstract
Emerging evidence suggests that clozapine, an atypical
antipsychotic, limits co-occurring alcohol and cannabis
abuse in patients with schizophrenia. Data regarding the
potential effects of other atypical antipsychotics regarding
their beneficial effects in these patients appear to be less
dramatic. The broad pharmacologic profile of clozapine,
including a weak dopamine D2 receptor antagonism and
important effects on noradrenergic activity, may underlie
its effects in these patients. This session will delineate
recent studies in alcohol-preferring animals shedding
light on the potential mechanism of action of clozapine in
co-occurring patients.
Biography
Alan I. Green, M.D., Raymond Sobel Professor of
Psychiatry, Professor of Pharmacology and Toxicology and
Chairman of the Department of Psychiatry at Dartmouth
Medical School, received his BA from Columbia College
and his MD degree from the Johns Hopkins University
School of Medicine. Following an internship in medicine
at the Beth Israel Hospital in Boston, he was a research
associate at NIMH and was Director of Biomedical
Research at the Special Action Office for Drug Abuse
Prevention in the Executive Office of the President. He
did his psychiatry residency and a clinical research
fellowship at the Harvard-based Massachusetts Mental
Health Center. He joined the Harvard faculty in 1984
and was Director of the Commonwealth Research Center
at Harvard Medical School from 1987 until he came to
Dartmouth in 2002. Dr. Green’s research program, which
involves clinical and neurobiological studies of patients
with schizophrenia, particularly those with co-occurring
substance use disorders, medication development studies
for patients with alcoholism, and studies of alcohol
drinking animals, has been funded by a series of grants
from NIH, NARSAD and industry. He and his colleagues
have proposed a neurobiological model suggesting that
co-occurring substance use disorder in patients with
schizophrenia relates, at least in part, to deficiencies in
dopamine-mediated brain reward circuits. Data from
his group have suggested that the novel antipsychotic
medication clozapine limits alcohol and other substance
use in these patients; he has proposed that the unique
effects of clozapine in these patients relates to the
mechanism of action of the drug, including its effects in
brain reward circuits. On-going studies are continuing
to probe the optimal psychopharmacological strategies
for patients with co-occurring disorders through clinical
trials, neuroimaging studies, and a series of investigations
in animals.
Major Psychoses and Substance Abuse
49
Abstracts and Biographies
Sunday 26th April 2009 Chairman: Prof. Torgny H. Svensson, Sweden
16.00 – 17.30 Sidlaw Room
Parallel Session 8: Clozapine and comorbid substance abuse in schizophrenia:
Mode of action and novel leads
Prof. Helen M. Pettinati, USA
A double-blind, placebo-controlled pilot trial of quetiapine for the treatment of
Type A and Type B alcoholism
Abstract
These are results from a placebo-controlled pilot study
of quetiapine for reducing drinking in alcohol dependent
patients. There were 61 male and female alcohol
dependent patients that were randomized for 12 weeks
to either 400mg/day quetiapine or placebo. All patients
received supportive medical management. Quetiapinetreated patients reduced their amount of drinking (p=0.03),
compared to those taking placebo. More quetiapinetreated (31%) compared to placebo-treated (6%) patients
were abstinent throughout treatment (p=0.01). We also
report an interaction between quetiapine and alcohol
subtype -- Type B alcoholics (more difficult to treat than
Type A) drank less if they had been treated with quetiapine
than placebo.
This was an investigator-initiated, single-site study
supported by AstraZeneca Pharmaceuticals LP.
Biography
Helen M. Pettinati, PhD, is a Professor in the Department
of Psychiatry and the Director of the Treatment Research
Division at the University of Pennsylvania School of
Medicine. Her current research focuses on novel
strategies for treating alcohol and drug dependence,
with a particular focus in the area of pharmacotherapy.
She primarily receives grant support from the National
Institute on Alcohol Abuse and Alcoholism (NIAAA) and
the National Institute on Drug Abuse (NIDA). Both are
part of the National Institutes of Health (NIH).
Dr. Pettinati is currently the Director of a NIDA-funded
P50 Medication Development Center entitled: Innovative
Approaches for Cocaine Pharmacotherapy. She also was
a Principal Investigator on one of the largest national
pharmacotherapy trials published to date for treating
alcoholism, the COMBINE study, sponsored by NIAAA. Dr.
Pettinati has been a Fellow in the American Psychological
Association since 2000. From 2000 to 2001 she was an
Advisor both to the American Psychiatric Association DSMIV Study Group on Substance Abuse and to the Initiative
on Managing Alcohol Problems in Primary Care Settings
within the Department of Health and Human Services.
Author of over 150 scientific papers, books and book
chapters, Dr. Pettinati is the lead Editor of the COMBINE
Methods Supplement published by the Journal of Studies
on Alcohol in 2005, and the lead author of the Medical
Management manual published by the NIAAA/NIH in
2004. The Medical Management manual provides some
structured guidance to medical practitioners who prescribe
pharmacotherapy to alcohol dependent patients. Since
1987, Dr. Pettinati has been listed in the Who’s Who in
Emerging Leaders in America, and she was elected into
the John Morgan Society at the University of Pennsylvania
in 2002.
Dr. Pettinati received her advanced degree from the
Medical College of Pennsylvania in 1979 after graduating
summa cum laude from Drexel University in 1973.
50
Collegium Internationale Neuro-Psychopharmacologicum
Sunday 26th April 2009 Chairman: Prof. Andreas Heinz, Germany and Prof. Gunter Schumann, UK
16.00 – 17.30 Fintry Room
Parallel Session 9: Alcohol
Prof. Gunter Schumann, UK
Genetic findings in alcoholism - role of the glutamatergic system
Abstract
Interdisciplinary Research Group Addiction, MRC-SGDP
Center, Institute of Psychiatry at King’s College, POB 080,
London SE5 8AF, England
[email protected]
Glutamatergic neurotransmission is implicated in alcoholdrinking behavior in animal models. To investigate whether
genetic variations in glutamatergic neurotransmission
genes, which are known to alter alcohol effects in
rodents, contribute to the genetic basis of alcoholism in
humans, we performed an association analysis of alcohol
dependence and haplotype-tagging single nucleotide
polymorphisms (SNPs) covering 10 glutamatergic genes.
Resequencing of functional domains of these genes
identified 204 SNPs. Haplotypes with a frequency of
5% or greater could be discriminated by 21 haplotypetagging SNPs analyzed for association in 2 independent
samples of alcohol-dependent 1337 adult patients and
1555 controls as well as 144 adolescent trios recruited in
four university medical centers in the south of Germany.
Genotype profiles for GLAST; N-methyl-d-aspartatereceptor subunits NR1, NR2A, and NR2B; MGLUR5;
NNOS; PRKG2; CAMK4; the regulatory subunit of PI3K;
and CREB were analyzed for association with alcohol
dependence using multivariate statistical analysis. Risky
adolescent drinking was tested using the transmission
disequilibrium test. Analysis of study 1 revealed that NR2A
and MGLUR5 have the greatest relevance for human
alcohol dependence among the genes selected with
odds ratios of 2.35 and 1.69, respectively. Replication
analysis in study 2 confirmed an association of alcohol
dependence with NR2A (odds ratio, 2.01) but showed no
association with MGLUR5. Combined analysis of study 1
and study 2 exhibited a more significant association on
the Cochran-Mantel-Haenszel test (P < .001) for NR2A;
NR2A was associated with positive family history, early
onset of alcoholism, and maximum number of drinks in
adults as well as risky drinking patterns in adolescents.
Biography
Born in Germany, Professor Gunter Schumann studied
medicine at the University of Hamburg. In 2004 he
finished his Habilitation in Molecular biological and
genetic studies of signal transduction pathways and their
relevance for psychiatric diseases as shown for Alzheimer`s
dementia and alcohol dependence. In 2005, Professor
Schumann was appointed Chair of Addiction Biology at
the Institute of Psychiatry, at King’s College, London. He is
coordinator of IMAGEN, a pan-European research project
which aims to identify and learn more about biological
and environmental factors that might have an influence
on mental health in teenagers using a multicentric gen
x neuroimaging study of 2000 adolescents in several
European countries. Professor Schumann is also Deputy
Director of the NIHR-Biomedical Research Centre (BRC)
in Mental Health, based at the IoP and South London and
Maudsley NHS Foundation Trust (SLaM).
Professor Schumann is married and has one child.
Major Psychoses and Substance Abuse
51
Abstracts and Biographies
Sunday 26th April 2009 Chairman: Prof. Andreas Heinz, Germany and Prof. Gunter Schumann, UK
16.00 – 17.30 Fintry Room
Parallel Session 9: Alcohol
Prof. Rainer Spanagel, Germany
Metabotropic glutamate receptors and alcohol seeking and relapse
Abstract
Rainer Spanagel CIMH Mannheim, Germany
Several studies indicate a crucial role of group I
metabotropic glutamate receptors subtype 5 (mGluR5)
in relapse behaviour. We studied the effects of 2-methyl6-(phenyl-ethynyl)-pyridine (MPEP) - a mGlu5 receptor
antagonist - in the reinstatement procedure of ethanolseeking behavior by drug-associated cues and in the
alcohol deprivation model in long-term ethanol consuming
rats. MPEP attenuated ethanol-seeking significantly and in
a dose-related manner. In the second set of experiments a
sub-chronic treatment with MPEP resulted in a significant
and dose-dependent reduction of the alcohol deprivation
effect (ADE). For understanding the neuroanatomical
substrate mediating the effects of MPEP we have now
generated a new conditional knock-down model with
an RNAi approach in dopaminoceptive neurons (D1
receptor) and show that these mouse mutants exhibit
attenuated reinstatement of drug-seeking behaviour
when presented with a drug-paired cue. In conclusion,
D1 receptor containing neurons within the striatum are
critical for relapse behaviour.
Biography
1982-1984: University of Tübingen/
Intermediate diploma in biology
1985-1989: Technical University of Munich /
Diploma in biology
1988-1989: Max Planck Institute of
Neuropharmacology, Martinsried /
Diploma work
1989-1991: Max Planck Institute of
Neuropharmacology, Martinsried /
Dissertation, Ph.D (Prof. Albert Herz)
1991-1995: Max Planck Institute of Psychiatry, Munich /
Scientific assistant (Prof. Florian Holsboer)
1996-1999: Max Planck Institute of Psychiatry, Munich /
Head of the research group “Drug
Addiction”
1997: University of Munich / Habilitation in
Pharmacology & Toxicology
(Prof. Wolfgang Forth)
1999: Professor for Psychopharmacology at the
52
University of Heidelberg / Central Institute of
Mental Health (CIMH) / Mannheim
2000: Department head of Psychopharmacology at the
Central Institute of Mental Health (CIMH)
Awards: INVEST NIDA Award 1995
Wilhelm Feuerlein Award for Alcohol
Research 1998
Sir Hans Krebs Award 2003
Albrecht-Ludwig-Berblinger Award 2005
James B. Isaacson Award 2008
Diploma work: Microdialysis studies in freely
moving rats
Ph.D. thesis: Modulation of the mesolimbic
dopaminergic system of rats by
endogenous opioid systems
Habilitation: An animal model of alcoholism:
Neuropharmacological studies
on behaviour
Selected publications:
Spanagel R, Herz A, Shippenberg TS (1992) Opposing
tonically active endogenous opioid systems modulate the
mesolimbic dopaminergic pathway. Proc Natl Acad Sci
USA, 89:2046-50
Timpl P*, Spanagel R*, Sillaber I, Kresse A, Reul JM,
Stalla J, Planquet V, Steckler T, Holsboer F, Wurst W.
(1998) Impaired stress response and reduced anxiety
in mice lacking a functional corticotropin-releasing
hormone receptor 1. Nature Genet, 19:162-66 *equally
contributed
Sillaber I, Rammes G, Zimmermann S, Mahal B,
Zieglgänsberger W, Wurst W, Holsboer F, Spanagel R
(2002) Enhanced and delayed stress-induced alcohol
drinking in mice lacking functional CRH1 receptors.
Science, 296:931-33
Abarca C, Albrecht U, Spanagel R (2002) Cocaine
sensitization and reward are influenced by circadian
genes and rhythm. Proc Natl Acad Sci USA, 99:9026-30
Collegium Internationale Neuro-Psychopharmacologicum
Spanagel R, Sigmund S, Cowen M, Schroff KC, Schumann
G, Fiserova M, Sillaber I, Wellek S, Singer MV, Putzke J
(2002) The neuronal nitric oxide synthase (nNOS) gene is
critically involved in neurobehavioral effects of alcohol. J
Neurosci, 22:8676-83
Spanagel R, Pendyala G, Abarca C, Zghoul T, SanchisSegura, Magnone MC,Lascorz J, Depner M, Holzberg D,
Soyka M, Schreiber S, Matsuda F, Lathrop M, Schumann
G, Albrecht U (2005) The circadian clock gene Period2
alters the glutamatergic system and thereby modulates
alcohol consumption. Nat Med, 11:35-42
Sanchis-Segura C, Borchardt T, Vengeliene V, Zghoul
T, Bachteler D, Gass P, Sprengel R, Spanagel R (2006)
Involvement of AMPA receptor GluR-C subunit in alcoholseeking and relapse. J Neurosci, 26: 1231-1238
Wiens F, Zitzmann A, Lachance MA, Yegeles M, Pragst
F, Wurst FM, von Holst D, Guan SL, Spanagel R (2008)
The missing drink: the bertam palm of West-Malaysis gets
wild mammals to chronically consume alcohol. Proc Natl
Acad Sci USA 105: 10426-10431
Engblom D, Sanchis-Segura C, Bilbao-Leis A, Dahan
L, Perreau-Lenz S, Balland B, Mameli M, Rodriguez
Parkitna J, Parlato R, Sprengel R, Lüscher C, Schütz G,
Spanagel R (2008) Glutamate receptors on dopaminergic
neurons control the persistence of drug-seeking. Neuron
59: 497-508
Bilbao A, Rodriguez Parkitna J. Engblom D, Sanchis-Segura
C, Perrau-Lenz S, Schneider M, Konopka W, Westphal
M, Breen G, Desrivieres S, Klugmann M, Bading H,
Rodriguez de Fonseca F, Vallada H, Schumann G, Schütz
G, Spanagel R (2008) Loss of the Ca2+/calmodulindependent protein kinase type IV in dopaminoceptive
neurons enhances behavioral effects of cocaine. Proc
Natl Acad Sci USA [Epub ahead of print]
Major Psychoses and Substance Abuse
53
Abstracts and Biographies
Sunday 26th April 2009 Chairman: Prof. Andreas Heinz, Germany and Prof. Gunter Schumann, UK
16.00 – 17.30 Fintry Room
Parallel Session 9: Alcohol
Dr Florian Schlagenhauf, Germany
Reward system dysfunction in alcoholism and schizophrenia
Abstract
A dysfunction of the dopaminergic reward system has
been postulated in the pathophysiology of both alcohol
dependency and schizophrenia.
Dopamine release in the ventral striatum is stimulated
by different drugs and thus reinforce drug consumption.
Alcohol abuse may “hijack” mesolimbic circuitry, leading
to increased salience to drug-associated cues at the
expense of conventional reward-indicating cues. Detoxified
alcoholics failed to activate the ventral striatum during the
anticipation of conventional monetary rewards, and this
decreased activation was associated with alcohol craving.
On the other hand, alcoholics displayed increased ventral
striatal activation to alcohol cues which was associated
with the severity of alcohol craving.
A subcortical hyperdopaminergic state in unmedicated
schizophrenia patients has been associated with the
pathogenesis of positive symptoms and a prefrontal
hypodopaminergic state with cognitive and negative
symptoms. Recent neuroimaging findings in schizophrenia
patients confirmed dysfunctional activation during
reinforcement learning. A blunted ventral striatal response
during reward anticipation was associated with the severity
of negative symptoms in unmedicated schizophrenia
patients. On the other hand, the attribution of aberrant
salience may contribute to the formation of delusions
in schizophrenia. During reward delivery we found a
differential impairment of ventral striatum and MPFC
during processing in drug-free schizophrenia patients
which was associated with delusions. Furthermore,
functional connectivity between both regions was reduced
in schizophrenia patients.
54
Biography
Dr. Florian Schlagenhauf, M.D., M.A., studied medicine
and philosophy at the University of Düsseldorf, Zurich
and Tel Aviv. He is post-doctoral research fellow at the
Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin (Chair: Prof. Andreas Heinz)
and is co-leader of the research group for functional
neuroimaging in schizophrenia.
Collegium Internationale Neuro-Psychopharmacologicum
MONDAY 27th APRIL
Monday 27th April 2009
Chairman: Prof. Wolfgang Fleischhacker, Austria
09.00 – 10.00 – Pentland Auditorium
Plenary Session 3:
Prof. Alan I. Green, USA
Schizophrenia and Substance Abuse: Approaching Pharmacotherapy
Abstract
Co-occurring substance use disorder complicates the
treatment of schizophrenia. Typical antipsychotics do not
appear to limit substance use or misuse in these patients.
However, a number of lines of evidence suggest that
the atypical antipsychotic clozapine may decrease their
substance use. Moreover, a number of other medications
used for the treatment of substance use disorders may
be helpful in combination with certain antipsychotics.
These data will be reviewed and a potential model
for the development of new treatment approaches will
be proposed.
Biography
Alan I. Green, M.D., Raymond Sobel Professor of
Psychiatry, Professor of Pharmacology and Toxicology and
Chairman of the Department of Psychiatry at Dartmouth
Medical School, received his BA from Columbia College
and his MD degree from the Johns Hopkins University
School of Medicine. Following an internship in medicine
at the Beth Israel Hospital in Boston, he was a research
associate at NIMH and was Director of Biomedical
Research at the Special Action Office for Drug Abuse
Prevention in the Executive Office of the President. He
did his psychiatry residency and a clinical research
fellowship at the Harvard-based Massachusetts Mental
Health Center. He joined the Harvard faculty in 1984
and was Director of the Commonwealth Research Center
at Harvard Medical School from 1987 until he came to
Dartmouth in 2002. Dr. Green’s research program, which
involves clinical and neurobiological studies of patients
with schizophrenia, particularly those with co-occurring
substance use disorders, medication development studies
for patients with alcoholism, and studies of alcohol
drinking animals, has been funded by a series of grants
from NIH, NARSAD and industry. He and his colleagues
have proposed a neurobiological model suggesting that
co-occurring substance use disorder in patients with
schizophrenia relates, at least in part, to deficiencies in
dopamine-mediated brain reward circuits. Data from
his group have suggested that the novel antipsychotic
medication clozapine limits alcohol and other substance
use in these patients; he has proposed that the unique
effects of clozapine in these patients relates to the
mechanism of action of the drug, including its effects in
brain reward circuits. On-going studies are continuing
to probe the optimal psychopharmacological strategies
for patients with co-occurring disorders through clinical
trials, neuroimaging studies, and a series of investigations
in animals.
Major Psychoses and Substance Abuse
55
Abstracts and Biographies
Monday 27th April 2009 Chairman: Prof. Robin Murray, UK
10.30 – 12.00 Pentland Auditorium
Study Group 1: Cannabis use and the presentation and outcome of psychosis
Dr Zerrin Atakan, UK
Cannabis use in those with severe mental illness: What can be done?
Abstract
In this study group, initially there will be a brief presentation
when the existing research evidence on psychological and
pharmacological interventions to manage cannabis use in
those with severe mental illness will be discussed. Substance
specific intervention is a newly developing area and but
there is some research emerging to guide clinicians on how
to manage this highly prevalent combination; cannabis
use in SMI. At the presentation the significance of early
psychoeducation, types of psychological interventions,
including motivational interviewing and their impact, as
well as pharmacological approaches will be discussed.
This presentation will then focus on a case study to discuss
how to help a 32 year old, Afro-Caribbean man, with a
criminal record and bipolar disorder. He is currently well,
but continues to use cannabis, almost on a daily basis,
whilst being an in-patient at a medium secure unit.
Biography
From 1990 until 2003, Dr. Zerrin Atakan was a psychiatric
intensive care consultant in Lambeth, London, providing
care to highly disturbed patients with severe mental
illness. From 2003 until August 2007, she was Lead
Consultant at the National Psychosis Unit at the Maudsley
and Bethlem Royal Hospitals where she provided care
to those with treatment resistant psychosis. She currently
is an Honorary Senior Lecturer and a Senior Researcher
at the Institute of Psychiatry where she studies the effects
of cannabis compounds on brain regions, as well as
developing an intervention model to treat those with
severe mental illness who continue to use substances. She
also does private practice.
Over the years she has developed particular expertise in
the management of patients with severe mental illness
and complex needs and the effect of cannabis on mental
health. As well as having written numerous publications
on these topics, she makes frequent presentations on
good practice in rapid tranquillisation, managing complex
needs patients, violence, treatment resistant psychoses
and the effects of cannabis and other substances on
severe mental illness and its management.
Her research interests include; severe mental illness,
management of violence, the effects of cannabis
compounds on brain and development of an intervention
model to improve the physical well being and reducing
substance use in those with severe mental illness.
56
Collegium Internationale Neuro-Psychopharmacologicum
Monday 27th April 2009 Chairman: Prof. Robin Murray, UK
10.30 – 12.00 Pentland Auditorium
Study Group 1: Cannabis use and the presentation and outcome of psychosis
Dr Wiepke Cahn, The Netherlands
Biography
Current Post
Chief Psychiatrist Schizophrenia Program, University
Medical Center Utrecht.
Assistant Professor Rudolf Magnus Institute of
neurosciences, Utrecht, The Netherlands
Previous Posts
1996-2000 Consultant psychiatrist Schizophrenia Unit
1995-1996 Registrar in Psychiatry at the UMCUtrecht.
1991-1995 Senior House Officer and Registrar in
Psychiatry at the United Medical and Dental School of
Guy’s and St. Thomas’ Hospitals, London, UK
Activities
Dr. Wiepke Cahn is the chief psychiatrist of the psychosis
and schizophrenia program, at the University Medical
Center Utrecht and an assistant professor at the
Rudolf Magnus Institute of neurosciences, Utrecht, The
Netherlands. Her main activity and interest is to unravel the
underlying neurobiological mechanisms of schizophrenia
through neuroimaging and genetic research. She has set
up and is involved in various national and international
multicenter research projects and is currently supervising
10 PhD students. Dr. Cahn is an editor of ‘Tijdschrift voor
Psychiatrie’ and is author of 50 papers and bookchapters.
Her non-research-based activities consist of treating (firstepisode) patients with schizophrenia and trying to prevent
the occurrence of psychoses in high risk patients.
Major Psychoses and Substance Abuse
57
Abstracts and Biographies
Monday 27th April 2009 Chairman: Prof. Andreas Heinz, Germany
10.30 – 12.00 Sidlaw Room
Study Group 2: ETOH
Dr Florian Schalgenhauf, Germany
Reduced activation during reward anticipation in the ventral striatum correlates
with impulsivity in alcoholics
Abstract
Beck A*, Schlagenhauf F*, Wüstenberg T, Hein J, Kienast
T, Kahnt T, Schmack K,
Knutson B, Heinz A, Wrase J
Alcohol dependence is often associated with impulsivity,
which may be correlated with dysfunction of the brain
reward system. In this study the association between
functional brain activation during anticipation of
incentive stimuli with impulsiveness was tested. Detoxified
alcoholics and age-matched healthy men participated
in a functional magnetic resonance imaging (fMRI)
study using a monetary incentive delay task (MID), in
which visual cues predicted that a rapid response to a
subsequent target stimulus would either result in monetary
gain, avoidance of monetary loss or no consequence.
Impulsivity was assessed with the Barratt Impulsiveness
Scale (BIS-10). Detoxified alcoholics showed reduced
activation of the ventral striatum during anticipation of
monetary gain relative to healthy controls. Low activation
of the ventral striatum and anterior cingulate during gain
anticipation was correlated with high impulsivity, only
in alcoholics, not in controls. This study suggests that
reduced ventral striatal recruitment during anticipation of
conventional rewards in alcoholics may be related to their
increased impulsivity, and raise questions about whether
this dysfunction might respond to treatment.
Biography
Dr. Florian Schlagenhauf, M.D., M.A., studied medicine
and philosophy at the University of Düsseldorf, Zurich
and Tel Aviv. He is post-doctoral research fellow at the
Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin (Chair: Prof. Andreas Heinz)
and is co-leader of the research group for functional
neuroimaging in schizophrenia.
* contributed equally
58
Collegium Internationale Neuro-Psychopharmacologicum
Monday 27th April 2009 Chairman: Prof. Andreas Heinz, Germany
10.30 – 12.00 Sidlaw Room
Study Group 2: ETOH
Prof. Rainer Spanagel, Germany
Alcoholism – A Systems Approach from Molecular Physiology to
Addictive Behaviour
Abstract
Rainer Spanagel CIMH Mannheim
Alcohol consumption is an integral part of daily life
in many societies. The benefits associated with the
production, sale and use of alcoholic beverages come
at an enormous cost to these societies. The World Health
Organization ranks alcohol as one of the primary causes
of the global burden of disease in industrialized countries.
Alcohol-related diseases, especially alcoholism, are the
result of cumulative responses to alcohol exposure, the
genetic make-up of an individual and the environmental
perturbations over time. This complex gene x environment
interaction, which has to be seen in a life-span perspective,
leads to a large heterogeneity among alcohol-dependent
patients, in terms of both the symptom dimensions and
the severity of this disorder. Therefore, a reductionistic
approach is not very practical if a better understanding
of the pathological processes leading to an addictive
behaviour is to be achieved. Instead, a systems-oriented
perspective in which the interactions and dynamics of
all endogenous and environmental factors involved
are centrally integrated, will lead to further progress in
alcohol research. This presentation adheres to a systems
biology perspective such that the interaction of alcohol
with primary and secondary targets within the brain is
described in relationship to the behavioural consequences.
As a result of the interaction of alcohol with these targets,
alterations in gene expression and synaptic plasticity take
place that lead to long-lasting alteration in neuronal
network activity. As a subsequent consequence, alcoholseeking responses ensue that can finally lead via complex
environmental interactions to an addictive behaviour.
Biography
Address: Zentralinstitut für Seelische Gesundheit (ZI)
Abt. Psychopharmakologie
Universität Heidelberg
J5
68159 Mannheim
Tel.: 0621/17036251
FAX: 0621/17036255
Email:[email protected]
www.zi-mannheim.de
1982-1984: University of Tübingen/
Intermediate diploma in biology
1985-1989: Technical University of Munich /
Diploma in biology
1988-1989: Max Planck Institute of
Neuropharmacology, Martinsried /
Diploma work
1989-1991: Max Planck Institute of
Neuropharmacology, Martinsried /
Dissertation, Ph.D (Prof. Albert Herz)
1991-1995: Max Planck Institute of Psychiatry, Munich /
Scientific assistant (Prof. Florian Holsboer)
1996-1999: Max Planck Institute of Psychiatry, Munich /
Head of the research group “Drug
Addiction”
1997: University of Munich / Habilitation in
Pharmacology & Toxicology
(Prof. Wolfgang Forth)
1999: Professor for Psychopharmacology at the
University of Heidelberg / Central Institute of
Mental Health (CIMH) / Mannheim
2000: Department head of Psychopharmacology at the
Central Institute of Mental Health (CIMH)
Awards: INVEST NIDA Award 1995
Continued...
Major Psychoses and Substance Abuse
59
Abstracts and Biographies
...Continued
Wilhelm Feuerlein Award for Alcohol
Research 1998
Sir Hans Krebs Award 2003
Albrecht-Ludwig-Berblinger Award 2005
James B. Isaacson Award 2008
Diploma work: Microdialysis studies in freely
moving rats
Ph.D. thesis: Modulation of the mesolimbic
dopaminergic system of rats by
endogenous opioid systems
Habilitation: An animal model of alcoholism:
Neuropharmacological studies
on behaviour
Selected publications:
Spanagel R, Herz A, Shippenberg TS (1992) Opposing
tonically active endogenous opioid systems modulate the
mesolimbic dopaminergic pathway. Proc Natl Acad Sci
USA, 89:2046-50
Wiens F, Zitzmann A, Lachance MA, Yegeles M, Pragst
F, Wurst FM, von Holst D, Guan SL, Spanagel R (2008)
The missing drink: the bertam palm of West-Malaysis gets
wild mammals to chronically consume alcohol. Proc Natl
Acad Sci USA 105: 10426-10431
Engblom D, Sanchis-Segura C, Bilbao-Leis A, Dahan
L, Perreau-Lenz S, Balland B, Mameli M, Rodriguez
Parkitna J, Parlato R, Sprengel R, Lüscher C, Schütz G,
Spanagel R (2008) Glutamate receptors on dopaminergic
neurons control the persistence of drug-seeking. Neuron
59: 497-508
Bilbao A, Rodriguez Parkitna J. Engblom D, Sanchis-Segura
C, Perrau-Lenz S, Schneider M, Konopka W, Westphal
M, Breen G, Desrivieres S, Klugmann M, Bading H,
Rodriguez de Fonseca F, Vallada H, Schumann G, Schütz
G, Spanagel R (2008) Loss of the Ca2+/calmodulindependent protein kinase type IV in dopaminoceptive
neurons enhances behavioral effects of cocaine. Proc
Natl Acad Sci USA [Epub ahead of print]
Timpl P*, Spanagel R*, Sillaber I, Kresse A, Reul JM,
Stalla J, Planquet V, Steckler T, Holsboer F, Wurst W.
(1998) Impaired stress response and reduced anxiety
in mice lacking a functional corticotropin-releasing
hormone receptor 1. Nature Genet, 19:162-66 *equally
contributed
Sillaber I, Rammes G, Zimmermann S, Mahal B,
Zieglgänsberger W, Wurst W, Holsboer F, Spanagel R
(2002) Enhanced and delayed stress-induced alcohol
drinking in mice lacking functional CRH1 receptors.
Science, 296:931-33
Abarca C, Albrecht U, Spanagel R (2002) Cocaine
sensitization and reward are influenced by circadian
genes and rhythm. Proc Natl Acad Sci USA, 99:9026-30
Spanagel R, Sigmund S, Cowen M, Schroff KC, Schumann
G, Fiserova M, Sillaber I, Wellek S, Singer MV, Putzke J
(2002) The neuronal nitric oxide synthase (nNOS) gene is
critically involved in neurobehavioral effects of alcohol. J
Neurosci, 22:8676-83
Spanagel R, Pendyala G, Abarca C, Zghoul T, SanchisSegura, Magnone MC,Lascorz J, Depner M, Holzberg D,
Soyka M, Schreiber S, Matsuda F, Lathrop M, Schumann
G, Albrecht U (2005) The circadian clock gene Period2
alters the glutamatergic system and thereby modulates
alcohol consumption. Nat Med, 11:35-42
Sanchis-Segura C, Borchardt T, Vengeliene V, Zghoul
T, Bachteler D, Gass P, Sprengel R, Spanagel R (2006)
Involvement of AMPA receptor GluR-C subunit in alcoholseeking and relapse. J Neurosci, 26: 1231-1238
60
Collegium Internationale Neuro-Psychopharmacologicum
Monday 27th April 2009 Chairman: Prof. Georg Winterer, Germany
10.30 – 12.00 Fintry Room
Study Group 3: Nicotine abuse in schizophrenia
Prof. Tony P. George, Canada
Translating Neuroscience to Tobacco Treatment in Schizophrenia:
The Devil is in the Details!
Abstract
Tony P. George, M.D., Division of Addiction Psychiatry, Department
of Psychiatry, University of Toronto and the Schizophrenia Program,
Centre for Addiction and Mental Health, Toronto, Canada
Tobacco addiction is the leading killer of people with schizophrenia.
Converging lines of evidence suggest that vulnerability factors
associated with schizophrenia risk may confer vulnerability to
high rates of tobacco use in this population, as well as their
difficulties with smoking cessation. A review of approaches to
tobacco treatment which have been informed by translational
neuroscience on nicotine and schizophrenia will be presented,
with an emphasis on the integration of pharmacological and
behavioral approaches. The emerging consensus is that tobacco
dependence is a treatable disorder in patients with schizophrenia,
and success will relate to a fuller understanding of biopsychosocial
factors associated with this co-morbidity.
Biography
Dr. Tony George is Professor of Psychiatry and Psychology,
Endowed Chair in Addiction Psychiatry at the University of
Toronto (U of T), and Head of Division of Addiction Psychiatry at
U of T. In April, 2008, he was appointed Clinical Director of the
Schizophrenia Program at the Centre for Addiction and Mental
Health (CAMH), where he leads CAMH’s largest clinical program
with over 420 staff, 45 physicians, 212 inpatient beds and nearly
5,000 outpatients treated at over 15 clinical sites across the
Greater Toronto Metropolitan Area.
Prior to coming to the University of Toronto and CAMH in
September, 2006, Dr. George was Associate Professor of
Psychiatry at Yale University School of Medicine in New Haven,
Connecticut USA, and Director of the Program for Research in
Smokers with Mental Illness (PRISM) at the Connecticut Mental
Health Center where he established the first clinical research
program in the world devoted to understanding and treating comorbid tobacco addiction and mental illness.
He completed his undergraduate and medical school training
at Dalhousie University in Halifax, Nova Scotia, Canada,
graduating with his M.D. degree in 1992. He then completed
psychiatry residency training (1992-96) and a fellowship in
Addiction
Neuroscience/Psychopharmacology
(1996-98)
at the Yale University School of Medicine in New Haven,
Connecticut, joining the faculty at Yale Medical School in 1998.
His research interests are focused on concurrent substance
abuse in serious mental illness including schizophrenia and
affective disorders, with an emphasis on tobacco and stimulant
dependence and addiction psychopharmacology. He also
has considerable experience studying the effects of drugs of
abuse on neurocognition in psychiatric patients. His research
program has been funded continuously for over 10 years by the
National Institute on Drug Abuse (NIDA), and he has received
nearly $8 million in competitive funding from NIDA and other
federal funding agencies since 1997, including three R01 series
operating grants and a NIDA Independent Scientist (K02) Award.
He also been awarded several prestigious grants and contracts
from numerous private foundations (including NARSAD) and
pharmaceutical companies, and most recently by the Canadian
Institutes of Health Research (CIHR) and the Canada Foundation
for Innovation (CFI). Dr. George also has over 120 peer-reviewed
publications, reviews, commentaries and book chapters, and his
scholarly work has been published in high impact factor journals
such as The Archives of General Psychiatry, The American Journal
of Psychiatry, Biological Psychiatry, Neuropsychopharmacology,
The Journal of Clinical Psychopharmacology, and Drug and
Alcohol Dependence.
He is a member of both the American and Canadian Psychiatric
Associations, and a full member of the American College of
Neuropsychopharmacology (ACNP). He was also one of the
charter members of the working group which produced the 2nd
edition of the American Psychiatric Association’s (APA) Clinical
Practice Guidelines on Substance Use Disorders (published in
April, 2007). He has also served as a member of numerous
grant review committees at the National Institute on Drug Abuse
(NIDA), including as a standing member of the NIDA Medications
Development Research Initial Review Group (NIDA-L) from 20012006. Dr. George edited the first book on pharmacotherapies for
tobacco dependence entitled “Medication Treatments for Nicotine
Dependence”, published in 2007. He is an Associate Editor for
the ACNP’s journal Neuropsychopharmacology, and is also on
the Editorial Boards of Psychiatric Times, The Asian Journal of
Psychiatry and The American Journal on Addictions. He is also a
member of the Council on Addiction Psychiatry of the American
Psychiatric Association (APA) and the Scientific Advisory Council
for the Canadian Council on Substance Abuse (CCSA). He is a
frequently consultant to addiction psychiatry and translational
neuroscience initiatives in the US, Canada and Europe, and a
frequent invited speaker at scientific conferences and psychiatry/
neuroscience grand rounds throughout the world. He is licensed
to practice medicine in Ontario and Connecticut, board-certified
in Psychiatry by the American Board of Psychiatry and Neurology
(ABPN), and is a Fellow in Psychiatry of the Royal College of
Physicians and Surgeons of Canada. Dr. George is listed with
“Best Doctors” in both the United States and Canada.
Major Psychoses and Substance Abuse
61
Abstracts and Biographies
Monday 27th April 2009 Chairman: Prof. Georg Winterer, Germany
10.30 – 12.00 Fintry Room
Study Group 3: Nicotine abuse in schizophrenia
Prof. Juergen Gallinat, Germany
Brain Imaging
Abstract
Study group brain imaging Charité University Hospital
Berlin
Department of Psychiatry, Campus Mitte, Charité
Gallinat et al.
The brain imaging group focuses on mechanisms of emotional
and cognitive stimulus processing in major psychiatric
diseases and the respective genetic underpinnings. In single
voxel MR spectroscopy a novel reliable methodology for
determination of absolute concentrations of glutamate in
the human brain has been established including advanced
metabolite quantification and error analysis. Glutamate
measures predict prefrontal brain function, psychiatric
disorders and personality traits. A combined measurement of
glutamate and fMRI within one session has been established
allowing multimodal imaging. Research on functional reward
processing with fMRI and its neurochemical correlates (PET,
MRS) is a main research field of the lab. Neuronal network
modeling has been established in collaboration with the
Bernstein Center of Computational Neuroscience Berlin.
Biography
Prof. Dr. Jürgen Gallinat *1966
since 2008 W2 Professor for Brain Imaging in Psychiatry
2002-2007 Senior Researcher Charité Clinic for
Psychiatry, Campus Mitte, MR imaging, MR
spectroscopy, Electrophysiology
2006
Habilitation: “Neurophysiological indicators
of neurotransmitter systems”
1998-2001 Postdoc Charité Clinic for Psychiatry
Charité Campus Benjamin-Franklin,
MR Spectroscopy, Electrophysiology
1996
Doctoral Thesis “Biology of Sensation
Seeking”
1994-1997 Clinician and Junior Research Fellow, Clinic
for Psychiatry, Ludwigs-Maximillians
Universität, Munich
Research Fields:
Prof. Dr. med. Jürgen Gallinat is leading the brain imaging
branch in the Department of Psychiatry, Charité University
Medicine Berlin His work focus on cognitive and mental disorder
including schizophrenia, affective disorders and addiction.
A main target is multimodal imaging employing functional
magnetic resonance imaging (fMRI), electrophysiology (EEG)
and magnetic resonance spectroscopy
62
(MRS). Using this approach, the impact of genetic variations
on cerebral function and structure (intermediate phenotype
approach) in healthy and diseased subjects was targeted
in several publications and grants (BMBF). The imaging of
cerebral glutamate, the role of brain derived neurotrophic
factor (BDNF) and nicotine for neuronal plasticity are major
research fields of the lab. Jürgen Gallinat is author and
coauthor of 130 scientific papers. A close collaboration
between the brain imaging group and the Bernstein Center
for Computational Neuroscience in Berlin is established.
This is driven by two BMBF grants which include the analyses
of multimodal imaging data with machine learning tools
(fMRI, MRS and positron emission tomography) focusing on
neuronal plasticity and learning.
Selected Publications:
Gallinat J, Ströhle A, Lang UE, Bajbouj M, Kalus P,
Montag C, Seifert F, Wernicke C, Rommelspacher H,
Rinneberg H, Schubert F (2005): Association of human
hippocampal neurochemistry, serotonin transporter genetic
variation, and anxiety. Neuroimage 26(1): 123-131
Neuhaus AH, Bajbouj M, Kienast T, Kalus P, von Haebler D,
Winterer G, Gallinat J (2006): Persistent dysfunctional frontal
lobe activation in former smokers. Psychopharmacology
186(2): 191-200
Gallinat J, Meisenzahl E, Jacobsen, LK, Kalus P, Bierbrauer
J, Kienast T, Witthaus H, Leopold K, Seifert F, Schubert F,
Staedtgen M (2006): Smoking and structural brain deficits: A
volumetric MR investigation. Eur J Neurosci 24: 1744-1750
Gallinat J, Götz T, Kalus P, Bajbouj M, Sander T, Winterer G
(2007): Genetic variations of the NR3A subunit of the NMDA
receptor modulate prefrontal cerebral activity in humans.
J Cogn Neuroscience 19: 59-68
Gallinat J, Kunz D, Lang UE, Neu P, Kassim N, Kienast T,
Seifert F, Schubert F, Bajbouj M (2007): Association between
cerebral glutamate and human behaviour: The sensation
seeking personality trait Neuroimage 34: 671-678
Lang UE, Hellweg R, Seifert F, Schubert F, Gallinat J (2007):
Correlation between serum BDNF levels and in vivo markers
of cortical integrity. Biol Psychiatry (in press)
Gallinat J, Obermayer K, Heinz A (2007): Systems
neurobiology of the dysfunctional brain: schizophrenia.
Pharmacopsychiatry Suppl. 1: S40-44
Lang U, Hellweg R, Sander T, Gallinat J (2008): The met
allele of the BDNF val66met polymorphism is associated
with increased BDNF serum concentrations. Mol Psychiatry
14: 120-122
Collegium Internationale Neuro-Psychopharmacologicum
Monday 27th April 2009 Chairman: Prof. Georg Winterer, Germany
10.30 – 12.00 Fintry Room
Study Group 3: Nicotine abuse in schizophrenia
Prof. Michael Wagner, Germany
Nicotine self-medication: beyond schizophrenia
Abstract
Co-authors: M. Wagner and G. Winterer
The
self-medication
hypothesis,
supported
by
epidemiological and experimental evidence, assumes
beneficial effects of nicotine on cognitive functions in
patients with schizophrenia. Employing data from a
large population based study (N > 1200), we examined
cognitive performance in non-deprived psychiatrically
healthy smokers and non-smokers. Mild but significant
deficits were found in several cognitive domains,
particularly for tests of spatial working memory and
perceptual speed. These deficits were more pronounced in
smokers reporting attention deficit symptoms. At least for a
subgroup of smokers, cognitive enhancement by nicotine
probably contributes to the initiation and maintenance of
smoking, similar as in schizophrenia. Some of the gene
variants associated with schizophrenia may underlie these
cognitive deficits also in non-psychiatric subjects.
Biography
Michael Wagner studied Psychology, Psychopathology
and Philosophy in Munich, where he obtained his Ph.D.
in Psychology in 1991. He then worked as an assistant
professor at the Department of Clinical Psychology at
the University of Constance. Since 1998 he is associate
professor of Psychology and directs the Neuropsychology
and Behavioural Neuroscience Unit at the Psychiatry
Department at the University of Bonn (Head: Prof. W.
Maier). His main research interests are endophenotypes
of psychiatric disorders as well as the pharmacology,
psychophysiology, and genetics of cognition, particularly
with regard to schizophrenia and nicotine.
Major Psychoses and Substance Abuse
63
Abstracts and Biographies
Monday 27th April 2009 Chairman: Prof. Georg Winterer, Germany
10.30 – 12.00 Fintry Room
Study Group 3: Nicotine abuse in schizophrenia
Prof. Veena Kumari, UK
Possible Mechanisms Mediating the Association between
Smoking and Schizophrenia
Abstract
The rate of smoking in schizophrenia is two- to four-fold
higher than the rate seen in the general population, with
a very low success rate in attempts to quit. The presence
of subclinical symptoms in healthy people manifesting as
schizotypal personality traits is also associated with an
increased smoking rate. Suggestions of beneficial effects
of nicotine specific to the schizophrenia population have
included that smoking may help to reduce the side effects
of antipsychotic medication, enhance the therapeutic effect
of antipsychotics, and improve illness-related deficits in
sensory and cognitive domains. A better understanding
of the reasons for the maintenance of smoking behaviour
would help to develop more effective (tailored) drug
and/or psychological therapies to help people with high
schizophrenia/schizotypy in their attempts to quit and/or
to provide them with an alternative without the harmful
effects associated with chronic smoking.
64
Biography
Veena Kumari is a cognitive experimental psychologist.
She obtained a PhD in Psychology from Banaras Hindu
University, India in 1993 and then moved to the Institute of
Psychiatry, London for post-doctoral research. She became
a Beit Memorial Research Fellow in 1999, a Wellcome
Senior Fellow in Basic Biomedical Science in 2002, and
Professor of Experimental Psychology in 2006. Her primary
research interests include the effects of pharmacological
and psychological therapies in psychotic disorders. She
has published over 100 peer reviewed data-based articles
in addition to several peer reviewed review articles, and
book chapters. She has received various international
and national awards for her research including the Young
Investigator Award from the National Alliance of Research
on Schizophrenia and Depression, USA (1999), and the
British Association of Psychopharmacology (BAP) GSK/
Clinical Psychopharmacology Prize (2002).
Collegium Internationale Neuro-Psychopharmacologicum
Monday 27th April 2009 14.00 – 15.30 Pentland Auditorium
Study Group 5: Bipolar
Prof. Robert H. Belmaker, Israel
Bipolar disorder and substance abuse
Abstract
RH Belmaker, MD
Ben Gurion University of the Negev, Beersheva, Israel
Bipolar disorder, especially among young adults, is
associated with high rates of substance abuse including
alcohol, marijuana, cocaine, heroin and nicotine.
Clearly, the extent of the substance abuse epidemic
and the characteristics of the particular substance most
commonly abused in a particular culture and social class
will affect use among bipolar patients in that culture and
social class as well. Most studies show that substance
abuse makes for a worse prognosis in bipolar disorder
although perhaps not in the inpatient treatment of the
manic phase. Alcohol abuse is associated with more
depressive episodes and marijuana abuse more often
triggers mania. The irregular life style, eating habits and
electrolyte imbalances associated with substance abuse
makes treatment with lithium and to some extent also with
oral anticonvulsants, more difficult. Recent hopes in this
area have centered on atypical antipsychotics as a possible
therapeutic advance in comorbid substance abuse and
bipolar disorder. However, two recent controlled trials
were only mildly encouraging.
The workshop discussion will center on the following
questions: 1) Can bipolar illness be stabilized before
substance abuse is successfully treated? 2) Can substance
abuse be successfully treated before bipolar disorder is
stabilized? 3) Is substance abuse a form of self treatment
in bipolar disorder or a symptom of pathology? 4)
Should substance abuse triggered by bipolar disorder be
diagnosed as a comorbidity or as a subtype of bipolar
disorder? The participants in the workshop will be
encouraged to present cases for discussion.
Biography
Dr. Belmaker received his BA from Harvard College in
1967 and his MD from Duke Medical School in 1971.
From 1972-74 he was a Clinical Associate at the National
Institute of Mental Health in Bethesda, MD. Since 1974
he has held positions in academic psychiatry in Israel,
first at the Jerusalem Mental Health Center 1974-1984
and then at Ben Gurion University of the Negev 1985 to
the present. Dr. Belmaker was a pioneer in biological
psychiatry in Israel, and chaired the International
College of Neuropsychopharmacology (CINP) meeting in
Jerusalem in 1982. His research interests include affective
disorders, especially mania, ECT, and second messenger
mechanisms. In 1993 he submitted a grant request to
National Alliance for Research on Schizophrenia and
Depression proposing that TMS could be therapeutically
useful in psychiatry, and was awarded the prestigious
Distinguished Investigator Award to pursue this hypothesis.
He has received the Anna Monika Prize for Research in
Depression (1983), the Ziskind-Somerfeld Prize for Senior
Research in Psychiatry (1993) and the European College of
Neuropsychopharmacology Lilly Research Award (1996),
and the National Alliance for Research on Schizophrenia
and Depression Lifetime Achievement Falcone Award for
research in affective disorder (2000) and the Research
Prize of the World Federation of Societies of Biological
Psychiatry (2004). Since 1998 he has been Associate
Editor of Bipolar Disorders. He is President of the CINP
(International College of Neuropsychopharmacology).
His hobbies include scuba diving and Biblical archaeology
in Israel.
Major Psychoses and Substance Abuse
65
Abstracts and Biographies
Monday 27th April 2009 Chairman: Prof. Alan I. Green, USA
14.00 – 15.30 Sidlaw Room
Study Group 6: Chronic psychosis
Dr Mary Brunette, USA
Abstract
Mr R. is a 37 year old divorced man who recently returned
to treatment. He started using alcohol at age 16, cannabis
at age 17, and cocaine at age 23. He started having
psychotic symptoms in his early 20s. He was admitted to
psychiatric units voluntarily five times in his 20s, and then
spent five years in prison for cocaine related charges. He
became homeless after his release from prison. He was
engaged into a residential treatment program where he
received intensive integrated treatment. He did well there
for six years. After leaving the program, both illnesses
relapsed. He recently decided to re-initiate treatment after
losing his housing again. He was started on olanzapine
and acamprosate. This case will provide the opportunity
to discuss proven and promising treatments for people
with co-occurring chronic psychosis and substance use
disorder, including antipsychotic medication, medication
for substance use disorders, stage-wise psychosocial
treatment approaches, group psychotherapy, residential
treatment, and contingency management.
66
Biography
Mary F. Brunette M.D. is Associate Professor of Psychiatry
at Dartmouth Medical School. She has been working
in the field of treatment for patients with co-occurring
disorders for 15 years. She conducts research on services
and medications for people with co-occurring substance
abuse and serious mental illness at Dartmouth Medical
School and is also a clinician who provides treatment
for patients with co-occurring disorders. In addition, Dr.
Brunette is Medical Director of the Bureau of Behavioral
Health in the Department of Health and Human Services
of New Hampshire, U.S.A., where she assists with
administration and policy development for this population.
She has authored over fifty articles and book chapters,
many related to treatment for people with co-occurring
disorders. She has received awards for teaching and
lectures nationally.
Collegium Internationale Neuro-Psychopharmacologicum
Monday 27th April 2009 Chairman: Prof. Alan I. Green, USA
14.00 – 15.30 Sidlaw Room
Study Group 6: Chronic psychosis
Prof. Tomas Palomo, Spain
Abstract
Thirty-six-year-old single male, lives with his parents,
diagnosed with paranoid schizophrenia. Illness onset at
age 17 (prodromal symptoms). First admission to hospital
at age 21, was diagnosed with adjustment disorder and
dissocial personality traits. Then received a diagnosis of
psychosis upon second admission (when aged 22). Has
required since then another 12 involuntary admissions
which follow the same pattern: lack of insight, poor
compliance with pharmacological treatment, irregular
follow-up in out-patient Mental Health Services. Was
referred to the Severe Mental Disorders Program at
“University Hospital Doce de Octubre” in June 2008, and
has followed a favourable course regarding insight and
treatment compliance.
research interest is the dopaminergic system and its
involvement in schizopsychotic and addictive disorders,
and, in relation to these, of personality disorders and
impulsivity. At present he is the national coordinator of
the schizophrenia programme of CIBERSAM (National
Spanish Research Net for Biomedical Research in Mental
Disorders) and member of its executive committee. He
was the Director of the Official School of Psychiatry from
1989 to 2004, and President of the Natonal Commission
of Psychiatry in Spain from 1995 to 2006.
MD by the Complutense University of Madrid in 1971,
PhD in neuroanatomy by the University of Valladolid in
1974. In 1971 his university activity begins as assistant
professor of Neuroanatomy at Valladolid Medical School
and since then has led multidisciplinary clinical-preclinical
investigation groups studying the cerebral basis of
psychiatric disorders in Spain and the United Kingdom.
Since he started research, clinical and teaching activities in
1971 he has been very active in promoting multidisciplinary
clinical-basic research in Spain. In 1993 he founded
the Fundacion Cerebro y Mente, multidisciplinary nonprofit organization dedicated to the promotion and
development of basic and applied neurosciences. He
has organized 27 national and international scientific
congresses in Spain on neuroscientific advances and
their relevance to psychiatry, and has published over 200
scientific publications. He is editor of the national series
of books “Avances Neurocientíficos y Realidad Clinical”
(10 volumes) and the international series: “Strategies for
Studying Brain Disorders” (9 volumes).
From 1976 to 1978 in MRC Brain Metabolism Unit at
Edinburgh he works on the molecular basis of Schizophrenia
using animal models of dopamine supersensitivity. From
1980 to 1984 in Aberdeen University he develops animal
models for the study of schizophrenia, depression and
addictive disorders.
At present he is in Madrid as Professor of Psychiatry in
the Complutense University of Madrid since 1985, Head
of Psychiatry Department at “University Hospital 12 of
October” since 1990, where he is also President of the
Scientific Committee, and President of the Foundation
Cerebro y Mente since 1993.
Biography
From 1979 he is Lecturer of Psychiatry in the Universities
of Newcastle (1979-1980), Aberdeen (1980-1984) and
from 1985 to the present, professor of Psychiatry in the
Complutense University of Madrid, Spain. From 1990
head of Psychiatry Department of “University Hospital 12
of October” of Madrid, he organized a Mental Health
Services Network to attend Area 11 of Madrid with 900,000
inhabitants and created a base of clinical and biological
investigation. At “University Hospital 12 of October” he set
up the Unit for the investigation and treatment of addictive
disorders (1995), organizes a research group for the study
of schizophrenia with neuroimaging techniques (1996), a
Unit for basic experimental neuropsychopharmacology
(1998) and the Unit for genetic studies (2002). His main
Major Psychoses and Substance Abuse
67
Abstracts and Biographies
Monday 27th April 2009 Chairman: Dr Carol Caton, USA
14.00 – 15.30 Fintry Room
Study Group 7: Substance-induced psychosis
Prof. Euphrosyne Gouzoulis-Mayfrank, Germany
Substance induced psychosis vs. dual diagnosis: Diagnostic considerations – The
case of hallucinogens and stimulants
Abstract
• Stimulant induced psychosis
• Hallucinogen induced psychosis
• Hallucinogen Persisting Perception Disorder (HPPD)
• Dual Diagnosis
Case I – Dual Diagnosis Schizophrenia and Amphetamine
Abuse manifestation of initial prodromal (negative)
symptom (differential diagnosis: depression)
self-medication of prodromal (negative) symptoms with
amphetamines
triggering of psychosis, manifestation of positive
symptoms
antipsychotic treatment
abstinence from amphetamines, antipsychotic treament,
symptom-free
discontinuation of medication, latency, re-manifestation
of negative symptoms
again self-medication with amphetamines, again
manifestation of positive symptoms
Biography
Professor Euphrosyne Gouzoulis-Mayfrank, M.D., born
1961, studied medicine in Mainz and was trained in
neurology, psychiatry and psychotherapy in the University
Hospitals of Freiburg and Aachen, Germany. From 1999
to 1993 she was Assistant Professor at the Psychiatric
Department of the University Hospital Aachen. From
2003 to 2008 she was full professor and vice director of
the Psychiatric Department of the University of Cologne.
She is now the Director of the Psychiatric LVR-Clinics
and associated Professor of Psychiatry at the University
of Cologne. Her main areas of research and interest
are the neurobiological acute effects of hallucinogens
and stimulants in humans, pharmacological models
for psychosis, neurotoxicity of designer drugs, and
treatment issues for comorbid patients with psychosis and
addiction.
Case II – Hallucinogen Persisting Perception Disorder
(HPPD)
use of cannabis, ecstasy and hallucinogenic mushrooms
for five years
flash backs
persisting visual abnormalities, pseudo-movements
of objects, sensitive to light, problems concentrating,
irritation, anxiety, feeling unreal; fluctuating intensity
abstinence, antipsychotic treatment with atypical and
typical antipsychotics
persistence of symptoms, depressive mood, social
withdrawal, self- medication with cannabis, exacerbation
of symptoms
discontinuation of antipsychotics, medication with
tranquilizer
gradual improvement, remission of symptoms within
8 months
68
Collegium Internationale Neuro-Psychopharmacologicum
Monday 27th April 2009 Chairman: Dr Carol Caton, USA
14.00 – 15.30 Fintry Room
Study Group 7: Substance-induced psychosis
Prof. Don Linszen, The Netherlands
Biography
Dr. Don Linszen, MD PhD is professor of Psychiatry at the
Academic Medical Center of the University of Amsterdam
(AMC-UvA) and director of the Adolescent Clinic of the
AMC-UvA in Amsterdam. His research interests include
the phenomenology of psychoses, schizophrenia and high
risk states of psychoses, the etiology and pathogenesis
of psychoses and schizophrenia, co-morbid cannabis
use and early recognition and pharmacotherapeutical
and psychosocial intervention in psychoses and
schizophrenia.
Linszen was member of the Amsterdam site of the steering
group of the “European Prediction of Psychosis Study
(EPOS).
At present he chairs the Dutch Health Care Fund sponsored
“Genetic Risk and Outcome of Psychosis (GROUP) study”
with as participants prof. R. Kahn (Univ Utrecht; prof.
J. van Os, Univ Maastricht ; prof. D. Wiersma, Univ.
Groningen). He is on the editorial board of the Journal of
Early Intervention in Psychiatry. With Jean Addington he
will organize the 7th congress of the International Early
Psychosis Association in Amsterdam in 2010.
Major Psychoses and Substance Abuse
69
Abstracts and Biographies
Monday 27th April 2009 Chairman: Dr Carol Caton, USA
14.00 – 15.30 Fintry Room
Study Group 7: Substance-induced psychosis
Prof. Andreas Heinz, Germany
Clinical aspects of dopamine-induced psychoses and their implications for the
dopamine hypothesis of schizophrenia
Abstract
Andreas Heinz
Department of Psychiatry and Psychotherapy, Charité –
Universitätsmedizin, Berlin
To date the biological basis for psychotic symptoms
in schizophrenia is still not well-explored. However,
abnormalities in neurotransmission have been found in
the brains of schizophrenic patients with focus on the role
of dopamine (DA). The “neuro-developmental dopamine
hypothesis” in schizophrenia proposes a mesolimbicmesocortical dopamine dysfunction. This is in line with
the fact that antipsychotic medication alleviates psychotic
symptoms by inhibiting the action of DA on DA D2
receptors. On the other hand psychotic symptoms can be
triggered by dopaminergic stimulation such as intake of
a variety of drugs e.g. amphetamine. Another example
of dopamine-induced psychosis occurs in the treatment
of Parkinson disease. However, studies showed that
symptoms of these dopaminergically induced psychoses
varied significantly from the psychopathological findings
of paranoid schizophrenic patients. These differences in
symptoms and clinical course of dopamine-induced and
schizophrenic psychosis do not support the hypothesis
that the pathogenesis of schizophrenic symptoms
can be explained only by a tonic hyperfunction of
dopaminergic transmission. Instead, the involvement
of other neurotransmitter system and their impact on
phasic dopamine release must be considered in order to
explain the pathogenesis of schizophrenic symptoms on
a neurobiological level.
70
Biography
Andreas Heinz, MD, studied medicine, philosophy and
anthropology at the Ruhr-Universität Bochum, Freie
Universität Berlin and Howard University, Washington
DC. Clinical education in neurology, psychiatry and
psychotherapy; research focus on reward system function
and dysfunction in alcoholism and schizophrenia and
on social and transcultural psychiatry. 2000 elected as
associate professor for addiction research, University
of Heidelberg, 2002 full professor, director and chair,
Charité - University Medical Center Berlin.
Collegium Internationale Neuro-Psychopharmacologicum
Monday 27th April 2009 Chairman: Dr Carol Caton, USA
14.00 – 15.30 Fintry Room
Study Group 7: Substance-induced psychosis
Prof. Michael First, USA
Substance use and psychosis: Diagnostic challenges and a case of
“Polysubstance Abuse”
Biography
Michael B. First M.D., is a Professor of Clinical Psychiatry
at Columbia University, is a Research Psychiatrist at the
Biometrics Department at the New York State Psychiatric
Institute. Dr. First was co-principal investigator on
the “Future of Psychiatric Diagnosis” conferences that
developed research agendas for the upcoming DSM-V
and ICD-11 revisions, was director of the DSM-V Prelude
Project, and is currently consulting with the WHO on the
ICD-11 revision.. Dr. First is the Editor of the DSM-IVTR, the Editor of Text and Criteria for DSM-IV, the APA’s
Handbook on Psychiatric Measures, and the Structured
Clinical Interview for DSM-IV (SCID).
Major Psychoses and Substance Abuse
71
RAFAELSEN YOUNG INVESTIGATORS TRAVEL AWARD
RAFAELSEN YOUNG
INVESTIGATORS
TRAVEL AWARD
In 1986 Ole Rafaelsen and William Bunney were instrumental in establishing. a CINP programme supporting the
attendance of young scientists at the XXVth CINP Congress in 1986. That programme was posthumously named the
Rafaelsen Fellowship Award to honour Dr. Rafaelsen, who died in 1987.
CINP are pleased to announce the winners of the Rafaelsen Young Investigators Award at the CINP Thematic Meeting on
Major Psychoses and Substance Abuse:
Ulrich Ettinger
Institute of Psychiatry, UK
Ulrich Ettinger studied psychology
at
Goldsmiths
College
and
neuroscience at the Institute of
Psychiatry. He wrote his PhD on
schizophrenia endophenotypes. In
2003 he moved to McGill University
on a Richard H. Tomlinson
Fellowship. In 2004 he returned to
the Institute of Psychiatry to work as
ESRC/MRC, Leverhulme, and NIHR fellow. Since January
2009 he heads a research group at the University of
Munich. His main research interests are (1) molecular
genetics of oculomotor, cognitive and neuroimaging
phenotypes, (2) pharmacological studies of oculomotor,
cognitive and neuroimaging variables with particular focus
on the prediction of inter-individual response variability
and (3) neural correlates of oculomotor control.
72
Leonora Long
Prince Wales Medical Research
Institute, Australia
Leonora started work as a pharmacist
practicing in hospital psychiatric
pharmacy
and
communitybased
opiate
dependence
pharmacotherapy dispensing. Her
PhD at Monash University built
on these interests, investigating
cannabis-based compounds in
rodent behavioural models of
schizophrenia symptoms. Following a postdoctoral position
at the University of Sydney she returned to investigating
cannabinoids in a genetic animal model of schizophrenia
with Schizophrenia Research Institute and Prince of Wales
Medical Research Institute. Future research aims are to
investigate the role of cannabinoids in regulating brain
development and to assess the impact of disruption of
this regulation, in conjunction with other environmental
and genetic risk factors, on adolescent and adult
mental health.
Collegium Internationale Neuro-Psychopharmacologicum
Celia Morgan
University College London, UK
Dr. Celia Morgan is currently a
post-doctoral research fellow at
University College London, from
where she received her Ph.D. in
2005. She currently works in the
Clinical Psychopharmacology Unit
with Professor Val Curran. Celia
is involved in various research
projects, chiefly investigating what
determines an individual’s vulnerability to the harmful
effects of cannabis use, but also diverse topics ranging
from the effects of alcohol on prospective memory,
the effectiveness of pharmacological compounds as
adjuncts to psychological therapy for addiction to the
neural correlates of semantic processing deficits in
schizophrenia. The topic of the current CINP thematic
meeting, Substance Misuse and Major Psychoses, marries
two of her major research interests and she is delighted
to have been awarded a Rafaelsen Young Investigator
Fellowship to attend.
Saddichha Sahoo
Emergency Management and Research
Institute (EMRI), India
Dr. Saddichha Sahoo is presently
working as Senior Research Fellow
in Clinical Research Division of
the Emergency Management and
Research Institute, Hyderabad,
India. He completed his psychiatry
residency training from Central
Institute of Psychiatry (CIP), India
and became a Member of Indian
Psychiatric Society, International Society for Bipolar Disorders
and the American College of Clinical Pharmacology.
His research area includes neuropsychopharmacology,
Schizophrenia, bipolar disorders, addiction, stigma and
community mental health. He is currently working on
exploring the links between substance use and psychosis.
He has over 50 academic publications in international and
national indexed journals and is on the review board of
10 international journals of psychiatry and public health.
He has won various awards including Siddartha Memorial
Award for Best Research Paper (2007), ISAD Travel Award
in Affective Disorders (2008), Society of Biological Psychiatry
(SOBP) Travel Award in Schizophrenia (2008), WFSBP
Young Investigator Award in biological psychiatry (2008),
WCTOH Scholarship in public health (2009) and recently
CINP Rafaelsen Young Investigators travel award (2009).
He is also the recipient of an IBRO Fellowship for training
in Functional genomics and presenting at the Hong Kong
Congress of Neuroscience 2009 held at Hong Kong.
Major Psychoses and Substance Abuse
73
RAFAELSEN YOUNG INVESTIGATORS TRAVEL AWARD
Christian Schubart
The Netherlands
Christian Schubart (1976) was
born in Haarlem, The Netherlands
and was raised in Spain and
Germany. He received his European
Baccalaureate from the European
School in Bergen, The Netherlands
(Cum Laude) in 1995. After a year
of volunteer work, he attended
the University of Amsterdam to
become a medical doctor. As a medical student he
worked in the Oxford-KEMRI-Wellcome Trust laboratory
in Kenya investigating the role of neurotropic viruses in
the clinical presentation of cerebral malaria. Shortly after
graduating from medical school, Chris started his clinical
residencies in psychiatry and is now parallelly working on
his doctorate in psychiatric genetics under the supervision
of Professor René Kahn. He is involved in several studies
focussing on the role of Gene Environment interplay
in the aetiology of psychotic disorders. The aim of his
current work is to identify genetic variation that underlies
the interaction between genes, cannabis use and the
risk to develop schizophrenia. Chris is a member of the
Scientific Advisory Board of the Netherlands Society of
Psychiatry and of the Board of Inspection of Psychiatric
Residencies. He has been a member of the organizing
committees of different international meetings in the field
of psychiatry and tropical medicine and has published in
several internationally peer reviewed journals.
74
Abiodun O. Adewuya
Lagos State University College
of Medicine, Nigeria
Dr Adewuya was the winner of
the Rafaelsen Young Investigators
Travel Award at the XXVI CINP
Congress in Munich. He was
unable to attend the Munich
meeting and we are pleased to
welcome him to Edinburgh to
collect his award.
Abiodun Olugbenga ADEWUYA
was born on January 1st, 1974. He had his MBChB
from the Obafemi Awolowo University (OAU), Ile-Ife
Nigeria in 1998. He had his psychiatry residency training
in Obafemi Awolowo University Teaching Hospitals
Complex (OAUTHC) and became a Fellow of the faculties
of psychiatry of both the West African College of Physician
(2006) and the National Postgraduate Medical College of
Physician (2007).
He is presently a Senior Lecturer at the Lagos State
University College of Medicine (LASUCOM) and a
Consultant Psychiatrist at the Lagos State University
Teaching Hospital (LASUTH), Nigeria.
He has over 40 academic publications in indexed journals
and an editorial board member of 4 international journals
of psychiatry. He has won various awards including Elli Lilly
Young investigators fellowship award in Bipolar disorders
(2007), GSK-ISBD Young Researcher travel award in
Bipolar disorders (2008), Schizophrenia International
Research Society travel award (2007), WHO-ISAM Travel
fellowship award (2008), and recently CINP Rafaelsen
Young Investigators travel award (2008).
His major research interests include Schizophrenia,
bipolar disorders, stigma and women mental health
Collegium Internationale Neuro-Psychopharmacologicum
Poster Abstracts
POSTER ABSTRACTS
The poster session will take place on Sunday 26th April 2009 at 17.30 – 19.00 in
the Strathblane Hall
P002
Co-occurrent mental and somatic diagnoses of treated
alcoholics in relation to long-term aftercare alcohol
abstinence and well-being Maja Rus-Makovec, Zdenka
Čebašek- Travnik University Psychiatric Hospital Ljubljana,
Centre for Alcohol Addiction Treatment, Ljubljana,
Slovenia
Objectives:
There are many evidences of co-morbidity influence
on alcohol addiction treatment outcome. We were
interested in question do alcohol dependent patients with
different co-occurrent mental and medical conditions
significantly differ in subjective attributes of well-being
and in abstinence rate two years after end of intensive
alcoholism treatment.
Method:
222 ex – patients participated in the research 24 months
after the end of intensive alcoholism treatment, 74 % of
them males (mean age = 46.17, SD = 8.79) and 26 %
females (mean age = 46.35, SD = 8.10).
Results:
No significant differences were found in any dependent
variable regarding any independent variable in »liver
disease« (yes/no); »presence of any somatic diagnose«
and »Personality disorders«. »Smokers vs. nonsmokers«,
so as »depressive vs. non depressive« differed significantly
only in evaluation of important interpersonal relations,
while »anxious vs. non – anxious« and »benzodiazepine
dependent vs. nondependent« significantly differed in
all self – evaluations, except in evaluation of important
interpersonal relations. Patients »with vs. without
liver cirrhosis« differed significantly only in perceived
psychological health (more positive self-evaluation in
cirrhosis). No significant differences were found between
(non)abstinents regarding any of eight categories of
mental disorder and medical conditions (yes/no) and no
significant differences were found in any self – evaluation
regarding the participation in different kinds of aftercare. Higher proportions of abstinents were found in
condition of after-care participations 24 months after end
of intensive treatment.
Conclusion:
Patients with different co-occurrent disorders did not differ
in abstinence rate. However, membership in after-care
24 months after the end of intensive therapy significantly
contributed to the abstinence rate. Abstinence was found
to be connected with more positive self-evaluations.
Patients with somatic co-occurrent diagnoses tended to
have more positive self-perceptions than patients with cooccurrent mental disorders.
P003
The Australian National Cannabis Prevention and
Information Centre
Jan Copeland (PhD)
National Cannabis Prevention and Information Centre,
University of New South Wales, Sydney, AUSTRALIA
The Australian National Cannabis Prevention and
Information Centre (NCPIC) is a unique government
response to cannabis use and related harms. NCPIC
directs it efforts to the reduction of the demand for
cannabis by preventing uptake and continuing use in the
Australian community. This is addressed by providing the
community with high quality, evidence-based information
on cannabis use, services such as an interactive website
and free national information and helpline, and building
the capacity of service providers to respond to the
intervention needs of cannabis users and their families.
NCPIC is a consortium that has brought together
individuals and organisations that have been working
in parallel for decades. It has assisted in the formation
of new collaborations between substance use research
Centres and clinical services with the mental health sector,
police, indigenous communities, and the media. The
Centre was officially opened on April 29th 2008. The
poster will describe the range of NCPIC activities to assist
mental health and substance use clinicians in the provision
of evidence-based information and interventions and
provide samples of a range of social marketing products
and clinical resources.
P004
Substance Misuse and Re-admission to a Scottish High
Security Psychiatric Hospital
Dr Manjunatha Anantharamu, Specialty Registrar in
Psychiatry, NHS Forth Valley, Scotland
It is a well-known fact that there is a higher prevalence
of substance misuse amongst the mentally ill, with the
highest prevalence found within mentally disordered
forensic populations. There is a well-established link
between substance misuse and violent and other criminal
Major Psychoses and Substance Abuse
75
Poster Abstracts
behaviour. This study was conducted in The State Hospital,
the high secure forensic psychiatric hospital for Scotland
and Northern Ireland.
Our aim was to measure the extent to which drugs and
alcohol were a contributing factor to re-admission to the
State Hospital, the extent these patients had contact with
drugs and alcohol services at The State Hospital and
its influence on re-admission. The study was conducted
by collecting electronic and case file data of patients
readmitted between April 2006 and March 2008. Out
of 85 hospital admissions in this period, 18 were readmissions. 13 (72%) re-admissions had drugs and
alcohol as a contributing factor in their re admission.
Of this cohort 7 (54%), had previous contact with drugs
and alcohol services at the State Hospital.
In 4 (36%) re-admissions with previous contact with
the service, drugs and alcohol were not a contributing
factor. Patients who had contact with the service stayed
out longer in the community after their first discharge by
a mean length of 10 months. Having contact with drugs
and alcohol services and being restricted in terms of legal
status acted as a protective factor against re-admission.
More research is needed to assess the extent of
involvement and impact of drug and alcohol services
following discharge from high secure care.
P005
Personality differences between primary psychoses and
substance induced psychoses
L. Díaz1, D. Martínez1, L. Morro1, G. Mateu1, A Bulbena2,
M. Torrens 1,2.
1
Unitat de Patologia Dual Institut d’Atenció Psiquiàtrica
Salut Mental i Toxicomanies (IAPs) Centre Forum-Hospital
del Mar, Barcelona. Spain.
2
Institut d’Atenció Psiquiàtrica Salut Mental i Toxicomanies
(IAPs) Centre Forum-Hospital del Mar, Barcelona. Spain.
Introduction:
Primary (PP) and substance-induced (SIP) psychoses
show differences in several issues as sociodemographics,
employment data, symptom severity and family substance
abuse. Several studies had suggested that exist an
specific personality profile in schizophrenic patients (high
scores on harm avoidance dimension [HA], low scores
on novelty seeking [NS], reward dependence [RD], selfdirectedness [SD] and cooperativeness [CO] dimensions,
in comparison with controls. Little is know about the
differences in personality between primary psychotic
disorders and substance induced disorders
Objective:
To describe differences in personality dimensions between
PP and SIP in a dual diagnosis unit, using TCI-R.
76
Methods:
We collected sociodemographic data and the scores of
the four temperament and three character dimensions
from the Temperament and Character Inventory Revised
(TCI-R). Psychiatric diagnoses were made through PRISM
Interview, Spanish version.
Results:
- 24 patients admitted with psychosis (87% males; mean
age 33,6+8,26 ) were assessed using TCI-R. Two
groups were performed: PP (N=14) and SIP (N=10).
- Significant differences have been found between PP
and SIP in some character subscales. PP showed
higher scores in two HA subscales (fear of uncertainty
[64,9 + 10,7 vs. 56,3 + 10,6; p<0.05], shyness
with strangers [61,6+6,4 vs 52,7+8,6; p<0,005]),
and in a CO subscale (pure-hearted principles [48+11
vs 39,1+9,3; p=0.05]). They also showed a lower
score in a SD subscale (resourcefulness [38,9+11,9 vs
47,9+8; p=0,05] . Some trends was noticed: PP
showed a higher score in HA dimension (64,8+10,7 vs
56,3+10,6; p=0,06), and a lower score in a RD
subscale (attachment vs detachment [44+10,7 vs
51,8+9,1; p=0,07].
Conclusions
- Significant differences have been found between both
groups (PP vs. SIP) in different character subscales.
- Some trends have been observed between both groups
(PP vs SIP) in a temperament dimension and in a
character subscale.
References:
-Hiroaki, H, Hiroko, N, Ryota, H, Nakabayashi, T,
Saitoh, O, Murray, R, Okabe, S, Kunugi, H. Personality
in schizophrenia assessed with the Temperament
and Character Inventory (TCI). Psychiatry Res. 2008;
160:175-183.
-Smith, MJ, Cloninger, CR, Harms, MP, Csernansky, JG.
Temperament and character as schizophrenia-related
endophenotypes in non psychotic siblings. Schizophrenia
Research. 2008; 104:198-205.
P006
Effect of litter origin on sensitivity of mice to ethanol
PAAVO POKK1 KAI ÕKVA2, TIMO NEVALAINEN3,4,
1Department of Pharmacology, Tartu University, 2Vivarium,
Tartu University, 3National Laboratory Animal Center,
University of Kuopio, Kuopio, Finland and 4Department
of Basic Veterinary Sciences, Veterinary Faculty, University
of Helsinki, Finland,
Since human alcoholism has a significant genetic
component, selected strains of laboratory animals with
different sensitivity to the effects of ethanol have been
introduced for animal studies. However, it is possible that
there are also individual differences in the sensitivity to
ethanol that depend on the litter origin of the animal. Our
Collegium Internationale Neuro-Psychopharmacologicum
aim was to assess whether such differences exist during
chronic ethanol exposure.
Male outbred mice (NIH/S) from 10 litters were evenly
allocated to control and chronic ethanol exposure groups.
During 39 days mice were housed in an inhalation
chamber and exposed to increasing concentrations of
ethanol in the inhaled air. The weight of control and
ethanol-intoxicated mice gradually increased. Starting
from day 3 the weight of mice exposed to ethanol
increased more than that of control mice (p = 0.025), this
effect was observed till day 35 (p = 0.040). Furthermore,
the litter origin of animals also had a significant effect on
weight changes both in control (p = 0.010 on day 35)
and ethanol-treated mice (p = 0.001 on day 35). Raising
blood ethanol levels slowly resulted in the development of
tolerance to the effects of ethanol. During the first 36 days
inhalation period no obvious signs of ethanol intoxication
(sedation, ataxia) were observed. Since blood ethanol
levels gradually increased, from the 37th day part of
mice became heavily intoxicated and had to be removed
from the box. Statistical analysis revealed that there were
significant differences between the sensitivity of mice
from different litters. Consequently, based on tolerance
the litters could be divided into low and high sensitivity
groups.
On the basis of our data it can be proposed that outbred
mice from different litters differ in their sensitivity to ethanol
and inclusion of the litter in statistical analysis can reduce
the number of animals needed to get reliable results.
P007
Comorbidity of substance abuse among schizophrenic
patients: a descriptive and comparative study
AUTHORS: Pérez-García, M.; Mozos-Ansorena, A.; TajesAlonso, M.; Martínez-Formoso, S.; Durán Maseda, M.J.;
Martínez-Gómez, P.; Portillo Díez, J.; Armas- Barbazán,
C.; Páramo-Fernández, M; Brenlla-González, J.; PortelaTraba, B.
Introduction:
Sustance abuse is by far the most common comorbid
problem among schizophrenic patients1. This supposes
a notorious difficulty in managing such patients and the
consequences are extreme. This patients are much greater
users of psychiatric services.2
Objective:
To describe and to compare the sociodemographic and
health differences of schizophrenic patients with or without
comorbid substance abuse.
Materials and Methods:
The sample is made up of 26 patients (average age
= 40.04±11.35 years); being 6 women and 20 men
who respond to the following inclusion criteria: be
admitted, at least on one occasion throughout their
psychopathobiographies, in the Acute Unit of Psychiatry
of the Conxo Hospital; comply with the ICD-10 criteria
for the diagnosis of schizophrenia; being the temporal
period of inclusion since October 2007 to July 2008.
Based on the objective, we separate our sample in
two groups depending on the absence (Group A) or
existence (Group B) of comorbid substance abuse. The
sociodemographic and health variables are analyzed
through a statistic package in the sample, using frequency
tables and distribution graphics.
Results:
A history of substance abuse was reported by 50% of
the patients. SOCIODEMOGRAPHIC PROFILE: The
prevalence of males in group B is a 84.6% vs 69.2 % in
group A. Nobody ended the university studies in group B
vs 7.7% in group A. In both groups prevail the pensioners
(>75%), unmarried state (84.6%), and most of them live
together with own family (>60%). HEALTH PROFILE: In
both groups prevail the paranoid schizophrenia (>75%).
The number of admissions in group B was higher but
the average hospital stay is lower (93.15±56.09 vs
124.62±97.35 days). In relation to the last admission
it has been motivated due to a wrong compliance of the
prescribed treatment in both groups (>84%). The main
difference was the type of admission that it was voluntary
in a 69.2% in group A vs 46.2%. Furthermore, in group
A the 76.9% has not been prescribed with any typical
antipsychotic (neither oral nor depot) but the 76.9% have
been prescribed with long-acting atypical antipsychotic vs
the 61.5% and the 69.2% respectively in group B. The
differences of antipsychotic dose are not relevant among
the groups.
Conclusions:
We coincide with the literature published up to the
date that 50 % of the schizophrenic patients presents
a comorbid substance abuse3, as well as that in the
substance abuse group vs absence group predominates
over the masculine sex, to have few studies, more frequent
psychiatric admissions, that does not exist difference of
antipsychotic dose4 , and in both groups, risperidone
is the long-acting antipsychotic most used, because it
has proved more effective than antipsichotics depot in
improving substance abuse and schizophrenia symptoms
in subjects with dual diagnosis5. But, in spite of more
compliance with atypicals supposed by the literature, in
the group B we find a higher propensity for typical drugs
vs group A6. Besides we do not coincide with the literature
that the duration of admission is longer in group B vs
group A4.
Bibliography:
1. Strakowski ,S.M.,Tohen, M., Stoll, A.L.et all.
Comorbidity in psychosis at first hospitalization.
American Journal of Psychiatry. 1993; 150,
752-757.
2. Jones P. B.; Buckley P. F. Schizophrenia. 2006.
Elsevier. Pág 109-112).
3. Alan S. Bellack. and Carlo C. DiClemente.
Treating Substance Abuse Among Patients With
Major Psychoses and Substance Abuse
77
Poster Abstracts
4. 5. 6. Schizophrenia American Psychiatric Association.
Psychiatr Serv 50:75-80, January 1999
Practice guidelines for the treatment of psychiatric
disorder compendium 2006. Pág 411-414 Vol 1.
Rubio G, Martínez I, Ponce G, Jiménez-Arriero
MA, López-Muñoz F, Alamo C. Long-acting
injectable risperidone compared with
zuclopenthixol in the treatment of schizophrenia
with substance abuse comorbidity. Can J
Psychiatry. 2006 Jul;51(8):531-9.
Janssen B, Gaebel W, Haerter M, Komaharadi
F, Lindel B, Weinmann S. Psychopharmacology
(Berl). 2006 Aug;187(2):229-36. Epub 2006
May 19. Evaluation of factors influencing
medication compliance in inpatient treatment of
psychotic disorders.
P009
DRD4 polymorphism predicts the effect of L-DOPA on
gambling behaviour
Christoph Eisenegger1, Daria Knoch1,2,3, Richard P. Ebstein4,
Lorena R.R. Gianotti5, Peter S. Sándor2, Ernst Fehr1,3
1
Institute for Empirical Research in Economics, Branco
Weiss Laboratory for Social and Neural Systems Research,
University of Zurich, Switzerland
2
Dept. of Neurology, University Hospital Zurich,
Switzerland
3
Collegium Helveticum, 8092 Zurich, Switzerland
4
Scheinfeld Center, Department of Psychology, Hebrew
University, Jerusalem
5
The KEY Institute for Brain-Mind Research, University
Hospital of Psychiatry, University of Zurich, Switzerland
A challenging question in the fields of neuroscience
and addiction research is why some individuals are
more vulnerable than others to addictive disorders.
Pharmacogenetic studies investigating how genetic
variation leads to differential drug response offer a way
to unravel this mystery.
In recent years, impulse control disorders, in particular
pathological gambling, have been described in Parkinson’s
patients; these problems are most likely associated with
dopaminergic treatment. Interestingly, only a subgroup
of Parkinson’s patients develops pathological gambling,
raising the question whether there might be an interaction
between genetic predisposition and dopaminergic drug
administration. By applying a pharmacogenetic approach
in 200 healthy subjects, we observed a differential effect
of dopaminergic stimulation using 300 mg of L-DOPA
on gambling behavior, depending on variation in the
dopamine D4 receptor gene. Carriers of the 7 repeats
allele of the DRD4 exon III variable number tandem
repeat polymorphism show an increased propensity
to gamble after dopamine modulation. These findings
may have implications for the dopaminergic treatment
of Parkinson’s disease patients by offering a genotype
approach for determining individual susceptibilities
for pathological gambling. They may also afford
78
insights into the vulnerability mechanisms underlying
addictive behavior.
P010
Effects of aripiprazole on insight and subjective
experience in individuals with an at-risk mental state:
an open-label trial
Hiroyuki Kobayashi1) 2), Keiko Morita3), Kiyoaki Takeshi3),
Haruo Kashima1), Masafumi Mizuno3)
1)
Department of Neuropsychiatry, School of medicine,
Keio University, Tokyo, Japan
2)
Tokyo-Musashino Hospital, Tokyo, Japan
3)
Department of Neuropsychiatry, School of medicine,
Toho University, Tokyo, Japan
Introduction:
Antipsychotic medication is often associated with adverse
effects that are particularly undesirable for young subjects,
such as pronounced weight gain and sexual dysfunction.
Therefore, medication with antipsychotic for the psychotic
prodrome has caused an ethical issue: such adverse
effects not only pose a risk to false-positive subjects but
may also lead to poor adherence. However, more recent
studies on psychotic prodrome have shown that some
novel antipsychotics are safer and more tolerable for
young people. This study was aimed to investigate whether
the administration of aripiprazole for the treatment of
psychotic prodrome would not only relieve the prodromal
symptoms but also be tolerable in a larger clinical sample
and to evaluate the effect of medication on improvements
in insight and subjective well-being.
Methods:
This study was performed at three sites: a university
hospital, a psychiatric hospital, and a community mental
health clinic. Participants were eligible for enrollment in
the study if they were between the ages of 16 and 40 years
and met the Criteria of Prodromal Syndromes (COPS).
The Structured Interview for Prodromal Syndromes (SIPS)
was performed for patients identified as having an ‘atrisk mental state’. Psychiatric measures included the
Scale of Prodromal Symptoms (SOPS) and the Global
Assessment of Functioning (GAF). The incidence of
akathisia was recorded using the Barnes Akathisia Rating
Scale (BARS). Transition to psychosis was operationally
defined using the Presence of Psychotic Symptoms (POPS)
criteria. Clinical insight was measured using the Scale to
Assess Unawareness of Mental Disorder (SUMD), and
changes in subjective-experience were assessed using the
Subjective Well-being under Neuroleptics Short version
(SWNS). Information on adherence to medication was
collected from not only participants but also their family
or caregivers. During the 1 week prior to beginning
study medication, participants underwent eligibility
and examinations. After beginning study medication,
participants were scheduled for eight weekly visits. Dosing
followed a flexible schedule. Institutional Review Board at
each site approved this procedure.
Collegium Internationale Neuro-Psychopharmacologicum
Results:
Thirty-four treatment-seeking ‘prodromal’ patients
(male, 36.0%; mean age, 23.4 ± 5.6 years) were
enrolled in this study. At the 12-week follow-up
point, 28 participants (82.4%) remained in the trial;
all these patients exhibited symptom alleviation and
an improvement in insight. Although their subjective
well-being scores improved significantly at 4 weeks,
however, they did not change significantly during the 8
weeks of treatment.
Conclusions:
This trial suggests that aripiprazole not only produces
a clinical benefit in prodromal subjects, but also results
in a high adherence to medication, with improvements
in insight and subjective well-being. These results also
support our hypothesis that adherence to medication might
be associated with patient insight and self-experience.
Although further placebo-controlled studies are needed,
aripiprazole might be a first-line treatment for individuals
at imminent risk for psychosis.
P011
The role of cannabis in cognitive functioning of patients
with schizophrenia
Thomas Schnell1, Dagmar Köthe, Jörg Daumann,
Euphrosyne Gouzoulis-Mayfrank
Cognitive deficits are commonly found both in patients
with schizophrenia (SCH) and in people with cannabis use
disorders (CUD). Surprisingly, some small recent studies
reported better cognitive performance in SCH patients
with comorbid cannabis use disorders (SCH+CUD)
compared to other SCH patients.
The aim of the present study was to investigate the residual
impact of CUD and specific patterns of consumption on
cognition in a larger sample of SCH+CUD patients.
We administered a cognitive test battery to 34 SCH and 35
currently abstinent SCH+CUD patients. We explored the
association between patterns of cannabis consumption
and cognitive performance. Potential confounds
with influence on cognitive ability were assessed and
controlled for.
SCH+CUD patients had poorer academic achievements
and lower vocabulary scores, but they performed better
in tests of verbal and working memory, visuomotor speed
and executive function. More frequent cannabis use was
associated with better performance in attention and
working memory tasks.
Although our findings might be interpreted as beneficial
effect of cannabis use on cognition in patients with
schizophrenia, we favour an alternative interpretation:
The better cognitive functioning of SCH+CUD patients
may rather reflect a relatively lower vulnerability to
psychosis compared to the SCH group. Lower vulnerability
may correspond to a higher level of functioning such as
cognitive ability. This conclusion is consistent with the view
of cannabis playing a critical role in the manifestation of
psychosis in at least some of the SCH+CUD patients.
Department of Psychiatry and Psychotherapy, University
Hospital of Cologne, Kerpener Str. 62, 50924 Cologne,
Germany; mail: [email protected]
1
P012
Neuroprotective effect of amitriptiline, haloperidol,
sulpiride at hippocampal and frontal cortex at rats
D. Marinescu, L. Mogoantă, T. Udriştoiu, I. Udriştoiu,
Ileana Marinescu, M. Pirlog
U.M.F. Craiova
Purpose of the study:
The depressive disorders with psychotic symptoms has
a high risk for neuroprotection decrease. This decrease
may be primary, determined by the unbalance of
neurotransmission and glicocorticoid hyperactivity, or
secondary to the antidepressants and mostly antipsychotics.
The use of antidepressants is frequently associated with
neurostructural changes and neuroplasticity decrease
through anticholinergic effects. Antipsychotic induced
hypodopaminergy through the long-term blockade of
the nigrostriatal D2 receptors. The hypodopaminergy
of the prefrontal cortex increases the cognitive
disfunction. Thalamo-amygdalian disconectivity can
aggravate depression and violent disruptive behaviour.
Hypercortisolemia is a valid animal model for stress
through dexametasone administration.
Methods used:
We formed 9 study lots (N1 – Dexametasone; N2 –
Haloperidole; N3 – Sulpiride; N4 – Dexametasone +
Aitriptiline, N5 – Dexametasone and Haloperidole; N6
– Dexametasone and Sulpiride; N7 – Dexametasone
and Haloperidole and Amitriptiline; N8 – Dexametasone
and Sulpiride and Amitriptiline; N9 – Control lot). Each
lot had 5 male adults rats (200-250g), held through
the study duration (21 days) in temperature, humidity,
food and ambient stressless conditions. The studied
substancies were administrated intraperitoneal, daily, for
21 days, saline solution equivalent to: amitriptiline (2mg/
kg/day) haloperidole (0.20mg/kg/day), dexametasone
(0.20mg/kg/day) and sulpiride (8mg/kg/day) in two
equal doses, at a 12 hour interval (08:00 – 20:00). In
day 11 and 21 the rats were sacrificed and the sample
brain was histopathologically processed through specific
colouring and fixation techniques and we evaluated the
neuroprotection comparing the cytoarchitectural changes
in frontal cortex and hippocamp.
Major Psychoses and Substance Abuse
79
Poster Abstracts
Results:
Frontal cortex and hippocamp were the most intensely
affected even since the 10th day after dexametasone,
amitriptiline and haloperidole and less affected
after sulpiride.
The association haloperidole - dexametasone and
amitriptiline - dexametasone induced intense pinocytosis
accompanied by vacuolisation with massive neuronal
loss at the VI, V, and IV frontal cerebral layers. The
pinocytosis and vacuolisation are also observed at the
hippocampal level.
Conclusions:
Haloperidole
has
a
significant
decrease
in
neuroprotection.
Sulpiride (first atipical antipsychotic) demonstrated an
neuroprotective effect.
The hypercortisolemia (dexametasone) and amitriptiline
amplifies the neuroprotection decrease through the
cholinergic blockade mechanisms. In the depressive
disorder with psychotic symptoms, we recommend the
association between antidepressant without anticholinergic
effects with atypical antipsychotics.
P013
Psychometric structure of pcl-r in alcoholic patients.
Guillermo Ponce, Mercedes Navío, Roberto Rodríguez,
Janet Hoenicka, Miguel Angel Jiménez-Arriero, Tomás
Palomo and the Psychosis and Addiction Research Group
(PARG)
Departarment of Psychiatry, University Hospital 12
Octubre, Madrid, Spain
CIBERSAM. Madrid, Spain
Introduction:
There is abundant literature regarding the use of the
Psycophathy Checklick Revised (PCL-R) in prison samples
but only a few investigations have been carried out in
samples with substance use disorders (SUD), and they
have yielded opposite results with respect to the factorial
structure of the scale.
Aims:
Evaluate the psychometric characteristics of PCL-R in a
sample with SUD, specifically alcohol dependence.
Methods: The study included 369 alcoholic patients
males who had requested detoxification in the Addictive
Behaviours Unit of the “12 de Octubre” Hospital, in Madrid
(UPRA). PCL-R was applied by trained Psychiatrists.
Results: The use of PCL-R in our sample exhibits a good
consistency (Cronbach’s alpha coefficient=0.94) and
reliability (kappa=0.88).Factorial analysis shows a
bifactorial structure with two potential facets for each one,
and variance for this four-factors solution was 78.33%.
Moreover, in our sample, PCL-R score did not follow a
normal distribution.
80
Conclusion: Our results shows psycopathy appears to be
a categorical condition by contrast with prison samples
with a great frequency of psychopathic individuals, or
community samples, with a very low rate of psycopathy.
References:
Hare RD, Harpur TJ, Hakstian AR, Forth AE, Hart
SD,Newman JP. (1990)The Revised Psychopathy Checklist:
reliability and factor structure. Psychological Assessment,
2, 338-341.
McDermott P.A., Alterman A.I., Caccioca J.S.Generality
of psychopathy Checklist- Revised factors over substance
dependent patients. J.Consult. Clin. Psychol. 2000;
Feb.68 (1).: 181-186
Patrick CJ, Hicks BM, Nichol PE, Krueger RF.A
bifactor approach to modeling the structure of the
psychopathy checklist-revised J Personal Disord. 2007
Apr;21(2):118-41
Ponce G, Hoenicka J, Jiménez-Arriero MA, RodríguezJiménez R, Aragüés M, Martín-Suñé N, Huertas E, Palomo
T.DRD2 and ANKK1 genotype in alcohol-dependent
patients with psychopathic traits: association and
interaction study Br J Psychiatry. 2008 Aug;193(2):121-5
Walters GD, Duncan SA, Mitchell-Perez K.The latent
structure of psychopathy: a taxometric investigation of
the Psychopathy Checklist Revised in a heterogeneous
sample of male prison inmates. Assessment 2007
Sep;14(3):270-8.
P014
Substance abuse and cognitive function in schizophrenia
Roberto Rodriguez-Jimenez(1,2), Alexandra Bagney(1), Isabel
Martinez-Gras(1,2), Guillermo Ponce(1,2), Janet Hoenicka(1,2),
Eva Maria Sanchez-Morla EM(3), Ana Aparicio(4), Maria
Aragues(1,2), Gabriel Rubio(1,2), Miguel Angel JimenezArriero(1,2), Jose Luis Santos(4), Tomas Palomo(1,2); and
Psychosis and Addictions Research Group(1).
(1) Servicio de Psiquiatría. Hospital Universitario
12 de Octubre. Madrid, Spain.
(2) CIBER de Salud Mental (CIBER-SAM), Instituto de
Salud Carlos III. Madrid, Spain.
(3) Hospital General Universitario. Guadalajara,
Spain.
(4) Hospital Virgen de la Luz. Cuenca, Spain.
Cognitive function in schizophrenia has been associated
with different factors, such as age, duration of illness,
number of previous psychotic episodes, negative
symptoms and positive symptoms. Substance use has also
been associated with cognitive function in schizophrenia.
However, contradictory results have been found regarding
the influence on cognition of comorbid substance use
disorders (SUDs), that is, of dual diagnosis. Our aim was
to study the relationship between cognitive (executive)
Collegium Internationale Neuro-Psychopharmacologicum
function and a) age, b) duration of illness, c) number of
psychotic episodes, d) positive symptoms, and e) negative
symptoms, in a sample of schizophrenic patients, and
secondly to study whether these relationships persisted
after stratification of the sample according to the presence
or absence of SUD history. A sample of 203 schizophrenic
patients were evaluated for psychotic symptoms using the
PANSS, and assessed using a neuropsychological battery
that included the Wisconsin Card Sorting Test, the Trail
Making Test, and the Stroop Task in order to calculate
a composite cognitive score of executive function. Linear
regression analyses were performed, with the cognitive
score as the dependent variable, and age, duration of
illness, number of psychotic episodes, positive PANSS
score and negative PANSS score as independent variables.
For the total sample, the regression model showed three
variables to be significant predictors of the cognitive
score: age (p=0.004), number of episodes (p=0.027),
and PANSS negative score (p=0.003). However, once
the sample was stratified, the regression model showed
age (p=0.011) and number of episodes (p=0.011) to be
predictor variables for the cognitive score in the group
of schizophrenic patients with SUD history, while age
(p=0.028) and PANSS negative score (p=0.006) were
predictors in the group of schizophrenic patients without
such history.
P015
Clinical differences in schizophrenia patients related to
substance abuse
M.T. Bel, A. Falces C. Conesa, V. Fabregat, R. Borrego,
A. Corominas.
Centre de Salut mental de Mollet del Valles- Hospital de
Mollet- Barcelona (Spain)
Objective:
By this study we want to see clinical differences between
schizophrenic patients in relationship to their previous or
continued alcohol and drug abuse.
Methods:
A sample of 45 patients who attended to a Psychiatric
Rehabilitation Center were tested for severity of illness
by using PANSS ( Positive and Negative Syndrome Scale
for Schizophrenia) at entering the study and 5 years later.
They are 14 women and 31 men , with a mean age of
37,58 years, Sd 6,81 , range 25 to 48 ys, had a mean
Total PANSS score of 66,64 , Sd 14,34 and after 5 years
of 58,76 , Sd 13,68. Previous alcohol abuse was recorded
in 20 patients (44,4%) from total sample, previous drug
abuse was recorded in 12 patients (26,7%). After 5
years alcohol was recorded for continued abuse in 11
patients (24,4 % ) and other drugs-mainly cannabis- were
abused in 7 patients (15,6%).
Results:
Relationship between PANSS score and alcohol and
substance abuse was tested by T-test and were significative
for previous ( Student’s T
-30,746; Sign <0,05)
and continued alcohol (Student’s T -28,873; Sig. <0,05)
and substance abuse in both times of study (Student’s
T for previous substance abuse -30,746; Sig. <0,05;
Student’s T for continued substance abuse -28,555;
Sig. 0,05)
Conclusions:
We conclude that abuse of drugs and alcohol leads to a
worse prognosis of illnes in schizophrenia as measured
by clinical status scales (PANSS).
Drugs use in schizophrenia can be postulated as a way of
self treatment of negative symptoms and anxiety caused
by illness.
P017
A DTI Tractography Study of the Cingulum Bundle in
Euthymic Bipolar I Disorder
Louise
Emsell1*,
Alexander
Leemans2,
Camilla
1
3
Langan , Gareth Barker , Wil. van der Putten1,
Peter McCarthy1, Rachel Skinner1, Colm McDonald1
and Dara M. Cannon1
1
Clinical Neuroimaging Laboratory, NUI Galway, Ireland,
2
CUBRIC,Cardiff, United Kingdom, 3Insitute of Psychiatry,
London, United Kingdom
Introduction:
Evidence from the field of structural neuroimaging
implicates subtle white matter abnormalities in bipolar
disorder (BD) in brain regions involved in affective
regulation and executive function. One region that
emerges consistently is the cingulate cortex. This
preliminary data DTI tractography study sought to identify
trait related white matter microstructural abnormalities in
the major white matter tract associated with the cingulate
cortex: the cingulum bundle, in an entirely euthymic cohort
of patients.
Method:
DTI data was acquired on 15 euthymic BD type I and 19
healthy control (HC) subjects using a 64 gradient direction
sequence, (b=1300) collected on a Siemens 1.5T MRI
scanner. Diagnosis of BD-I was determined by DSM-IV
SCID and euthymia confirmed both 1 month prior to, and
on the day of testing using the Beck Depression Inventory,
Altman Self-Rating Scale for Mania, Young Mania
Rating Scale and Hamilton Rating Scale for Depression
(threshold <6). Exclusion criteria for all subjects included
neurological or co-morbid psychiatric disorders, learning
disability, drug and alcohol abuse within the last year,
and loss of consciousness >5 mins. Ethical approval was
obtained from the University College Hospital Galway
(UCHG) Clinical Research Ethics Committee. All subjects
provided written informed consent.
Whole brain tractography was performed by a single
blinded rater using ExploreDTI (www.ExploreDTI.com) and
the cingulum bundle extracted using three ‘AND’ regionsof-interest (ROI) gates. Median fractional anisotropy (FA)
Major Psychoses and Substance Abuse
81
Poster Abstracts
and apparent diffusion coefficient (ADC) were calculated
for the dorsal portion of the cingulum between the anterior
and posterior gates.
Results:
Tractography reliability was determined by blinded retracking of bilateral cingula in 10 subjects (intra-class
coefficient >.95). There were no significant group
differences in age (p=0.999) or gender (p=0.798).
There was no significant difference in the mean median
FA or ADC between groups in either the left or the right
cingulum (p>0.05). There was however, a significant
effect of age on FA in the right cingulum (p=0.01). An
inter-hemispheric asymmetry (Left>Right) in FA but
not ADC was detected in both groups (T-paired=8.8;
p=3.5x10-10).
Discussion:
We detected left-sided laterality in the FA of BD and
HC groups which may reflect the known morphological
asymmetry of the cingulate cortex. However, this
preliminary sample size may not have provided the
power to detect group based differences in FA or ADC in
the cingulum bundle. Future work will expand the sample
size studied, incorporate parcellation of the cingulum
into sub-sections, such as rostral and parahippocampal
divisions, and explore High Angular Resolution Diffusion
Imaging (HARDI) based estimations of the diffusion
signal to improve the sensitivity of tractography
based analyses.
P020
Using single trial electroencephalography (EEG) and
functional Magnetic Resonance Imaging (fMRI) to
investigate the effects of nicotine on responses to a visual
oddball task in schizophrenics and controls.
T. Warbricka,b*, A. Mobaschera,b, J. Brinkmeyera,b,
F. Mussoa, T. Stoeckerb, G.R. Finkb,c , J.N. Shahb,
G. Winterer a,b
a
Neuropsychiatric Research Laboratory, Department
of Psychiatry, Heinrich-Heine University, Duesseldorf,
Germany
bInstitute of Neurosciences and Biophysics, Helmholtz
Research Center Juelich, Germany
c
Department of Neurology, University of Cologne,
Germany
Introduction:
The prevalence of smoking is much higher in schizophrenics
than in the general population. Given that nicotine can
improve performance on cognitive tasks it is possible that
schizophrenics use smoking as a form of self medication to
improve the cognitive deficits associated with schizophrenia.
Investigating the effects of nicotine on cognitive processes
is a key factor in understanding the role of nicotine use
in schizophrenics. There is evidence to suggest increased
noise, or variability, in electroencephalography (EEG)
and functional magnetic resonance imaging (fMRI) data
82
in schizophrenics compared to control subjects. Single
trial analysis of responses to cognitive tasks allows us to
investigate this variability across trials. Using simultaneous
EEG-fMRI we aim to investigate the effects of nicotine on
the single trial variability of responses to a cognitive task
in schizophrenics and control subjects.
Methods:
12 schizophrenics (7 smokers) and 15 controls (7 smokers)
performed a visual oddball task (reversing checkerboard)
after an acute challenge of 1mg nicotine or placebo.
EEG and fMRI data were recorded simultaneously during
the task. EEG data was corrected for scanner related
artefact using Brain Vision Analyzer 2. Single trial P3
amplitude values were then extracted for target stimuli.
We performed conventional General Linear Model
(GLM) analysis of the fMRI data using FSL. In addition we
included the single trial P3 amplitude as an additional
regressor in the GLM.
Results:
For schizophrenics and controls our conventional analysis
revealed activation in brain areas associated with target
detection tasks (pre-frontal, medial frontal and temporoparietal regions). Thus far our ongoing single trial analysis
has revealed additional activation in the central opercular
cortex, post central gyrus and insula for control subjects in
the placebo condition but not the nicotine condition.
Discussion:
Our preliminary results show that including single trial EEG
parameters in the analysis of fMRI data can differentiate
the effects of nicotine and placebo challenges on brain
activation patterns. This is achieved by modelling the single
trial variability of responses to a decision making task.
We suggest that the absence of additional EEG informed
activation in the nicotine condition is due to reduced
single trial variability. It is plausible that this reduced
variability is responsible for the improved attentional
performance that is often attributed to nicotine. Given the
evidence for additional noise/variability in EEG and fMRI
data from schizophrenics we anticipate a similar finding
for the single trial EEG informed analysis of data from
our schizophrenic group. We aim to provide evidence
for a mechanism by which nicotine improves attention in
schizophrenics.
P021
Differential activation of the attentional network by
nicotine in schizophrenics, healthy smokers and nonsmoking controls
A. Mobaschera,b, T. Warbrick a,b, J. Brinkmeyer a,b,
F. Mussoa, T. Stoeckerb, G.R. Finkb,c, J.N. Shahb, G.
Winterer a,b
aNeuropsychiatric Research Laboratory, Department
of Psychiatry, Heinrich-Heine University, Duesseldorf,
Germany
bInstitute of Neurosciences and Biophysics, Helmholtz
Collegium Internationale Neuro-Psychopharmacologicum
Research Center Juelich, Germany
cDepartment of Neurology, University of Cologne,
Germany
Introduction:
The proportion of smoking individuals amongst people
suffering from schizophrenia is substantially higher than
in the general population. There is also evidence that
this group of psychiatric patients may abuse nicotine
as a “self-medication” to treat some symptoms of their
disease, for instance cognitive deficits. In this ongoing
study the effects of acute nicotine on brain function during
the performance of an attentional task is studied.
Methods:
Thus far 36 subjects were investigated: 12 schizophrenics
(smokers and non-smokers), 12 non-smoking controls
and 12 smoking control subjects. Subjects performed a
visual oddball task (checker board reversal) after acute
challenge with 1mg nasal nicotine or placebo.
Echo-planar imaging using a 3T scanner was performed
to detect the task-related BOLD (blood oxygen level
dependent) effect. General linear model image analysis
was performed using SPM5. In the main analysis
infrequent target stimuli were contrasted with frequent
non-target stimuli.
Results:
We found activation of a distributed network of brain
regions, namely in the temporo-parietal, medial frontal,
and prefrontal cortex in response to target stimuli in all
3 groups. However, when the nicotine condition was
contrasted with the placebo condition different activation
patterns were obtained for the three groups. Moreover,
schizophrenics exhibited also deactivation in response to
nicotine in the left parietal cortex whereas no significant
deactivation was found in healthy smokers and nonsmokers.
Discussion:
Our preliminary data confirm that nicotine increases
the BOLD effect in structures of the attentional network
during task performance consistent with the notion of
an “activating” effect of nicotine. However, nicotine may
activate different regions in smokers and non-smokers.
Moreover our data suggest a more complex pattern of
activation and deactivation in schizophrenics.
from animal experiments. Similar results have been
demonstrated in humans (Lang et al. 2007). Smokers
with 10 hours abstinence of nicotine showed a significant
stronger inhibition in terms of short afferent inhibition
(SAI) and diminished intracortical facilitation (ICF). Here
we aimed to investigate if these differences of cortical
excitability between smoking and not smoking individuals
are caused and enhanced by nicotine consumption or if
smoking individuals reduce enhanced inhibition by acute
nicotine intake. Therefore different parameters of cortical
excitability were recorded before and after nicotine
consumption in smokers and nonsmokers.
Methods: 12 otherwise healthy smokers and nonsmokers
participated in our study. Cortical excitability was
investigated by means of paired pulse TMS and SAI before
and after administration of nicotine spray and nicotine
patch respectively.
Results:
Compared to nonsmokers, smokers showed a
significantely stronger SAI and diminished intracortical
facilitation before nicotine. After administration of
nicotine, intracortical facilitation in smokers increased
significantly, while nonsmokers showed a stronger
intracortical inhibition. With regard to SAI, smokers
showed no changes in inhibition after nicotine, whereas
nonsmokers had a stronger inhibition under nicotine.
Conclusions:
Our results suggest that nicotine can compensate
for diminished facilitation in smokers, probably by
compensating an excisting deficiency. Conversely, in
nonsmokers nicotine intake leads to increased inhibition.
These results argue for different acute effects of nicotine
on cortical excitability in smokers and nonsmokers.
P023
Ethnic Differences in the Prevalence of Substance Use in
First Episode Psychosis Patients
Jo Harta, Craig Morgana, Kim Donoghueb, Rodolfo
Mazzoncinic, Kevin Morgana, Paola Dazzana, Gillian
Doodyb, Gerard Hutchinsond, Peter B. Jonese, Robin M.
Murraya, Paul Fearona.
a
Institute of Psychiatry, Kings College London, UK;
b
University of Nottingham, UK; cUniversity of Verona,
Italy; dThe University of the West Indies, Trinidad and
Tobago; eUniversity of Cambridge, UK.
Different impact of nicotine on cortical excitability in
smokers and nonsmokers
Michael A. Nitsche, Bernd Dudda, Nicolas Lang, Walter
Paulus, Jessica Grundey
Georg-August-University, Dept. Clinical Neurophysiology,
Goettingen, Germany
Background:
There have been numerous reports of high rates of
psychosis in Black Africans and Black Caribbeans in the
U.K. One possible contributing factor proposed is high
levels of substance use, particularly cannabis use in Black
African and Black Caribbean populations. We sought to
examine the prevalence of substance use in a sample of
First Episode Psychosis (FEP) patients.
Objective:
Chronic nicotine intake influences cortical excitability
via functional and structural CNS changes, as known
Method:
We collected evidence on the prevalence of substance use
in a sample of First Episode Psychosis (FEP) patients, as
P022
Major Psychoses and Substance Abuse
83
Poster Abstracts
part of the AESOP study. Data relating to substance use
in the previous year were collected through interview and
case records.
Results:
We found that 49% of White British subjects used one or
more substances in the previous year (n=108), compared
with 48% of Black Caribbean (n=52; Adj. OR 1.01, 95%
CI 0.58-1.76) and 30% of Black African subjects (n=18;
Adj. OR 0.37, 95% CI 0.19-0.74). When we looked
specifically at cannabis use, we found that 44% of White
British subjects used cannabis in the previous year (n=97),
compared with 47% of Black Caribbean (n=51; Adj.
OR 1.27, 95% CI 0.73-2.12) and 28% of Black African
subjects (n=17; Adj. OR 0.45, 95% CI 0.22-0.89). All
odds ratios are adjusted for diagnosis, age, gender,
educational level and employment status.
Conclusion:
There was no evidence to suggest that substance use was
more common in any one ethnic group.
P025
P024
The prevalence of psychoses among in-patients with
alcohol related problems
Bodnar Boris, Breznoscakova Dagmar, Palova Eva
1st Department of Psychiatry, University Hospital, Kosice,
Slovak republic
Introduction:
Substance abuse is very common in people with any
psychiatric disorders even psychotic ones. Out of them
alcohol is still most frequently abused. Almost 50%
individuals with schizophrenia abuse either alcohol – 33%
or other drugs 27,5%. There is higher prevalence (3,8%)
of schizophrenia among people with alcohol dependence
than in general popultion (Regier et al., 1990). Alcohol
and drug dependence are very common also in patients
with bipolar affective disorder (Kessler et al., 1997). To
be able to differentiate in between „endogenous“ and
toxic psychosis is still an unmet need.
Patients and methods:
845 in-patients (650 men, 195 women) at the 1st
Department of Psychiatry in Kosice, Slovakia in years
1998-2002 were analyzed because of alcohol related
problems. Diagnoses of disorders related to alcohol
abuse and/or psychotic disorders were based on clinical
interview according to the International Classification
of Diseases – 10th revision. Data were obtained
retrospectively from patients´ files.
Results:
More than ¾ of the patients fit into diagnostic criteria for
alcohol dependence (active dependence or withdrawal
state). In group of male patients the diagnosis of
schizoaffective disorder (F25) was found in 0,3% and
nonorganic psychotic disorder (F28) in 0,2% patients. 0,5%
84
of female patients was diagnosed with schizoaffective
disorder (F25) and in the same proportion - 0,5% with
schizotypal disorder (F21). Bipolar affective disorder
(F31) was diagnosed in 0,2% of men and 1% of women.
Discussion:
Very low prevalence of psychotic disorders and actually
no schizophrenia was found in our sample of patients
with alcohol-related problems. Main reason why
comorbidity of psychotic disorders is so underestimated
is traditionally different approach to alcohol-related
problems. In case of schizophrenia or its relapse, for
example, alcohol dependence is usually considered to
be rather a complication of main disorder (psychosis)
than a separate diagnosis. That is why administratively
only psychosis is diagnosed. In past ‚social aspect“ was
considered, too – commorbidity with alcohol abuse could
result in loss of disability pension, so „dual-diagnosis“ in
patients with severe psychosis was avoided. As a result of
this approch we now can see extremly small number of
the patients with „dual-diagnosis“.
Superstitious conditioning can model delusions following
chronic but not acute ketamine
Freeman TP, Morgan CJA, Klaasen E, Das R, Stefanovic A,
Hunt S, & Curran, HV
The NMDA-receptor antagonist ketamine can induce
a range of psychotic-like symptoms such as delusions,
both when administered acutely and among drugfree recreational users. However it is not clear whether
‘acute’ or ‘chronic’ ketamine can provide a better model
of delusions in schizophrenia. Theoretically, delusion
formation in psychosis has been linked to elevated
levels of ‘superstitious conditioning’ or the erroneous
association of outcomes with events. The present study
aimed to objectively assess superstitious conditioning
following acute ketamine administration (experiment 1)
and among ketamine users (experiment 2). Experiment
1: used an independent groups, double blind design with
three groups: placebo (n=16), low dose ketamine (n=15;
75mg/kg), and high dose ketamine (n=16; 150mg/kg).
In the superstitious conditioning task, participants were
required to choose 2 out of 3 stimuli in order to score
the most points. However in each of the 72 trials the
points were awarded randomly, not contingent on actual
responses. Superstitious conditioning was measured as
the extent to which certain stimuli were chosen more than
others during the task, and whether ‘patterns’ were noticed
or not according to post task reports. No differences
were found in superstitious conditioning, despite dose
dependent ketamine-induced increases in PSI and BPRS
scores. Experiment 2: used an independent groups design
to assess superstitious conditioning among ketamine
users (n=17) polydrug users (n=19) and healthy controls
(n=18). Ketamine users were matched with polydrug
controls for drug use other than ketamine, and all groups
were matched for premorbid verbal IQ. Superstitious
Collegium Internationale Neuro-Psychopharmacologicum
conditioning was increased among drug users compared
to healthy controls, and among ketamine users compared
to polydrug controls, as indexed by choices made during
the task and post task reponses. The main findings of this
study were that acute ketamine did not induce changes
in superstitious conditioning among healthy volunteers,
yet repeated exposure to ketamine, and to a lesser
extent polydrug use, increased the propensity to adopt
superstious conditioning. This study replicated previous
findings of delusions in ketamine users using a novel,
objective measure, and is consistent with animal literature
suggesting that chronic NMDA receptor antagonism can
provide a better model of schizophrenia than acute. Due
to the cross-sectional nature of the study, it may be limited
by pre-existing differences among drug users, individual
differences in vulnerability to ketamine’s psychotomimetic
effects, and difficulties in quantifying lifetime drug use.
Nevertheless, if clinically validated, our novel task
assessing superstitious conditioning may have important
practical applications.
P026
Clinical characteristics of psychotic patients treated in a
community centre (CAS Barceloneta) for substance abuse
disorders in Barcelona
Castillo, C. Astals, M. Francina, F. Torrens, M.
Introduction:
CAS Barceloneta is an ambulatory treatment centre for
patients with any substance abuse or dependence disorder
in Barcelona (Spain). Placed in a general hospital,
attends some 300 new patients each year and the main
substances of abuse are Alcohol (45%), Cocaine (30%)
and Heroin (15%). Available data about prevalence of
psychiatric disorders in addicted patients suggests that
affective and anxiety disorders are the most frequent
diagnoses, personality and psychotic disorders are
less frequent.
Objective:
To describe a sample of psychotic patients with any
substance use disorder treated in a community centre for
substance abuse disorders.
Method:
The study included a total of 503 patients (73% males,
mean age: 43 years) who were in treatment in the last six
months in the centre. From the total studied population,
34 (7%) patients fulfilled criteria of any psychosis. The
socio-demographic data, psychiatric and toxicological
variables were recorded and a descriptive analysis was
carried out.
Results:
The main characteristics of the sample were: males
(85%), mean age: 39 years. Main psychotic diagnoses
were Schizophrenia, (47%), Substance Induced Psychotic
Disorder (20%), Delusional Disorder (12%), Schizoaffective
Disorder (12%), Psychotic Disorder NOS (6%) and
Schizophreniform Disorder (3%). Main substance use
dependence diagnoses were Heroin (41%), Alcohol
(29%), Cocaine (21%) and Cannabis (9%).
Conclusions:
The rate of psychosis diagnosis found in the sample was
similar to those described in previous studies.
Most of the psychotic disorders were in the group of heroin
dependence patients. It could be explained because they
were enrolled in a methadone maintenance treatment
program with a high retention rate.
P027
THE THERAPEUTIC MANAGEMENT OF SUBSTANCE
USERS WITH COMORBID PSYCHOTIC DISORDER IN
AN OUTPATIENT INDIVIDUAL PROGRAM FOR DRUG
ADDICTION TREATMENT
V. Koutras1,2,, L. Iliopoulou1,3, E. Fidi1, S. Thomos1, K.
Komninou1, S. Gonta1, D. Lagou1,
V. Basogianni1, A. Fotiadou3
1.
Counseling Center for Combating Drug Abuse Ioannina,
Greece (S.S.K.N.N.I.)
2.
University of Ioannina, Department of Preschool
Education, Greece
3. General Hospital of Ioannina “G. Hatzikosta”, Greece
Objectives:
In the present study we intend to show how the provision
of therapeutic services in an outpatient individual
psychotherapeutic program for drug addiction treatment
is influenced by the possibility of treatment of comorbid
psychotic disorders, and to suggest also effective practices
in this field.
Method:
The Counseling Center for Combating Drug Abuse
operates for fifteen years and constitutes the only service
for the treatment of drug addiction in our district. It is
a fact that in Greece substance users with comorbid
psychotic disorders are not usually acceptable in mental
health services or in drug addiction treatment centers.
The provision of therapeutic services to substance users
with comorbid psychosis came up as a need, since the
implications of psychosis to substance users are particularly
often (Kessler et al, 1994). A psychiatrist who works in
the program as an inside cooperator, collaborates for the
provision of these services.
The therapeutic procedure includes motivation for the
immediate interruption of substance use, diagnostic
approach, administration of antipsychotic treatment,
valuation of compulsory hospitalization, informing of and
cooperation with the family environment, administration
of naltrexone to heroin users, frequent sessions.
Results:
The parallel treatment of psychotic disorder and substance
abuse seems to be particularly important for the user’s
therapeutic progress.
Major Psychoses and Substance Abuse
85
Poster Abstracts
The complete abstinence from substance use ensures
remission of psychotic symptoms, or recovery in case
the disorder is drug induced, with the appropriate
administration of antipsychotic treatment (atypical
antipsychotics) and this secures more permanent
abstinence from substances in future. The acquisition of
empathy and the understanding of the effect of substances
in the emergence and therapy of psychosis – whether
psychosis preexists or comes as a result of drug use or
of withdrawal syndrome - have a positive impact in the
therapeutic process (Ziedonis et al, 2000).
The therapeutic alliance that will develop with the
attendant doctor, and the feeling of care and hope
that will be communicated to the user, are particularly
important elements for the holding in the therapy and the
compliance with medication.
Conclusions: Provision of integrated therapeutic services,
gives the possibility to a drug addiction treatment program
to address to all substance users, and also to take care
of many of the problems which can emerge during
treatment. Users with comorbid psychosis constitute a
high risk group regarding the holding in the therapy, the
relapse and their social exclusion. The demand for prompt
diagnosis and optimal patient management could be
accomplished by the cooperation of mental health and
drug addiction treatment services for the development of
treatment and hospitalization services for this particular
group of substance users.
References:
Kessler RC, McGonagle KA, Zhao S, et al: Lifetime and
12-month prevalence of DSM-III-R psychiatric disorders in
the United States: results from the National Comorbidity
Survey. Arch Gen Psychiatry 51:8-19, 1994.
Ziedonis D, Williams J, Corrigan P, et al: Management
of substance abuse in schizophrenia. Psychiatr Ann
30:67-75, 2000.
P028
Behavioural studies of Δ9-tetrahydrocannabinol and
cannabidiol in heterozygous transmembrane domain
Neuregulin 1 mutant mice
Leonora Long1,3,4, Rose Chesworth1,3,4, Jonathon Arnold1,2,
Tim Karl1,3,4
Schizophrenia Research Institute, Sydney, Australia.
School of Medical Sciences (Pharmacology) and Bosch
Institute, University of Sydney, Sydney, Australia.
3
Garvan Institute of Medical Research, Sydney,
Australia. 4Prince of Wales Medical Research Institute,
Sydney, Australia.
1
2
Objective:
Cannabis consumption is associated with increased risk
of developing schizophrenia in susceptible individuals.
We investigated the acute behavioural profiles of the
primary psychotomimetic constituent Δ9-THC and the
non-psychoactive phytocannabinoid cannabidiol (CBD)
86
in a battery of schizophrenia-relevant tests in adult
heterozygous transmembrane domain Neuregulin 1
mutant (Nrg1 HET) mice.
Methods:
Female Nrg1 HET mice and their wild type-like littermates
received injections of vehicle or Δ9-THC (5 or 10 mg/kg)
in a quasi-randomised, counterbalanced within-subjects
design. Male Nrg1 HET mice and their wild type-like
littermates received injections of vehicle or CBD (1 or
50 mg/kg) in a similar design. Following each injection,
mice were tested in measures of locomotor activity (open
field test), anxiety (elevated plus maze, light-dark test),
sensorimotor gating (prepulse inhibition) and working
memory (Y maze).
Results: Female Nrg1 HET mice displayed increased
baseline levels of locomotor activity, exploration and
anxiolytic-like behaviour. They were more sensitive to the
locomotor suppressant and anxiogenic effects of Δ9-THC
(5 mg/kg) in the open field test and less sensitive to the
anxiogenic effects of Δ9-THC (5 and 10 mg/kg) in the
light-dark test. Δ9-THC (10 mg/kg) enhanced prepulse
inhibition (PPI) in wild type-like mice but disrupted PPI at
5 mg/kg in Nrg1 HET mice. CBD (1 mg/kg) enhanced
PPI in both wild type-like and Nrg1 HET male mice, while
CBD (50 mg/kg) had no effect.
Conclusion:
Female Nrg1 HET mice are more sensitive to the acute
effects of Δ9 THC in several schizophrenia-relevant
behavioural tests. The effects on PPI appear to be sexspecific since they are in contrast with previous findings
in male Nrg1 HET mice. CBD, at a relatively low dose,
displays antipsychotic-like effects in sensorimotor gating,
extending findings from acute studies in rodents and
humans. Preliminary immunohistochemical analysis
suggests that CBD (1 and 50 mg/kg) alters the profile
of c-fos immunoreactivity produced by dexamphetamine
in the nucleus accumbens and prefrontal cortex. Analysis
of CBD-induced c-fos immunoreactivity in Nrg1 HET
mice will elucidate possible mechanisms for these
behavioural data.
P029
Insecure attachment and impulsivity-inattention problem
in adolescent with substance abuse or internet addiction
Young Sik Lee M.D.*, Ph.D., Sung Il Cho M.D.*,
Hyung Tae Baek M.D.*, Tae Young Choi M.D.**, Ph.D.
Bock Ja Ko M.D., Ph.D**.
*Department of Psychiatry, College of Medicine, ChungAng University Hospital, Seoul, Korea
**Department of Psychiatry, College of Medicine, Catholic
University of DaeGu, Daegu, Korea
***Seoul School Health Center, Seoul, Korea
Objectives:
In contrast to recent decline of smoking and alcohol
drinking in adults, those along with internet addiction in
adolescents are rapidly increasing, which have become a
Collegium Internationale Neuro-Psychopharmacologicum
major social issue around the world. Substance addiction
and behavior addiction such as internet addiction are
now assumed to have common biological causes.
Conduct disorder and attention-deficit hyperactivity
disorder, commonly known as ADHD, are the examples
of the well-known comorbid disorders or precursors of
substance abuse.
Formation of an insecure attachment will develop
negative beliefs that interact with genetic and biological
vulnerability and environmental risk factors, which causes
various behavioral problems and psychopathology in
adolescence and adulthood. Therefore, addiction in
adolescence can be speculated to have close relationship
with attachment formation.
Thus, this study was done to confirm the assumption that
insecure attachment formation and impulsivity-inattention
problems are major risk factors of addiction problems
in adolescent.
Methods:
Through mass surveys with Seoul School Health Centre,
255 adolescents in smoking or alcohol abstinence
program and 1,933 middle and high school students in
Seoul metropolitan area were assessed by self-reporting
scales: Adolescent Drinking Index(ADI), Fagerstrom
Tolerance Questionnaire, Young Internet Addiction Scale,
Revised Adult Attachment Scale(RAAS), and Conner and
Well’s self-reporting scale for ADHD(CASS). Subjects were
classified to 4 groups by presence of substance abuse or
internet addiction; non-addiction group, internet addiction
group, substance addiction group and combined internet
and substance addiction group.
Results:
Significant correlations were found between attachment
formation and internet addiction, in dependence,
anxiety, and closeness(r=-0.185, r=0.248, r=-0.147,
p<0.01, respectively). Impulsivity-inattention problems
had positive correlations with all of internet addiction,
alcohol dependence and nicotine dependence(r=0.345,
r=0.211, r=0.187, p<0.01). With attachment
formation, the four groups showed significant difference
in dependence(F=19.427, p<0.01), anxiety(F=28.926,
p<0.01), and closeness(F=12.853, p<0.01). The internet
addiction group and the substance-internet addiction
group showed lower scores in dependence and the
internet addiction group had the lower scores in closeness.
Anxiety was higher in the internet addiction group and the
substance-internet addiction group than other groups. In
addition, the four groups showed significant difference
in impulsivity-inattention problems(F=83.857, p<0.01),
of which the substance-internet addiction group showed
the highest scores, and the non-addicted group scored
the lowest.
Conclusion:
This study strongly suggests that insecure attachment
formation and impulsivity-inattention problems are the
major risk factors of adolescent addiction problems,
which may play some role in screening, preventing and
treating the addiction problems.
KEY WORDS: Adolescents’ addiction, Attachment,
Impulsivity-inattention problem
P030
Risk factors for the psychotic symptomatology in the
addiction disorder
Dr .Claudia Radut primary psychiatrist, Emergency Military
Clinical Hospital “Dr. Sefan Odobleja” Craiova Romania
Dr.Alexandru Tiugan Senior Lecturer, University for
Medicine and Pharmacy, Craiova ROMANIA
The neuro-biochemical modifications at the level of
cerebral citoarchitecture and in the dopaminergic,
serotoninergic and gabaergic system induced by the
disadaptative use of alcohol offer an etiopathogenic
support for the development of the acute or chronic
psychotic board.
Objectives:
Identification of vulnerability factors for psychotic
decompensations in alcoholism and their influence on the
evolution of basic pathology.
Methods and results:
In a retrospective study over 10 years on a number of 650
subjects fulfilling the DSM IV-R criteria for the addiction
disorder, a lot of 96 subjects was chosen (14,51%) with at
least one psychotic decompensation.
Out of them, 80% (53 subjects) manifested the presence
of a vulnerable somatic ground (modified hepatic
constants, epilepsy seizures, cerebral signs), and for
10% (10 subjects) the computerized tomography showed
ventriculomegaly and temporal – parietal atrophy.
The recurrence of the psychotic symptomatology was
observed 58 of the selected subjects (60%), most of them
with a second episode in the first two evolution years.
Conclusions:
Psychotic decompensations (especially the ethanol
withdrawal
with
perception
disorders)
appear
predominantly in patients with somatic vulnerability
(neurologic and hepatic influence).
The recurrence of the psychotic board is correlated
with some therapeutic resistance, with an increased
deterioration index and a quasi-permanent impulsiveness
and interpretative background.
Major Psychoses and Substance Abuse
87
Poster Abstracts
P031
Drug induced psychosis and first-episode primary
psychosis with concomitant drug abuse
Massimo C. Mauri, Filippo Dragogna, Ilaria F. De Gaspari,
Chiara Rovera, Alessandro Colasanti, A. Carlo Altamura
Department
of
Clinical
Psychiatry,
Clinical
Neuropsychopharmacology Unit, IRCCS Ospedale
Maggiore Policlinico Mangiagalli e Regina Elena, Via
F.Sforza 35, 20122 Milano, Italy
[email protected]
Co-occurrent drug abuse is a very frequent condition
among patients presenting their first episode of psychosis,
prevalence rates ranging between 25 and 60%.
The comorbidity of schizophrenia and substance abuse
is associated with more frequent relapses, more positive
symptoms and depression, cognitive impairment, and
a poorer outcome and treatment response. It has been
hypothesised that substance abuse could trigger psychotic
symptoms in vulnerable individuals.
The study included 48 patients at the first hospitalization
for psychosis diagnosed as Primary Psychotic Disorder
with comorbid Drug Abuse (PPDA) and Substanceinduced Psychotic Disorder (SIPD) following DSM-IV TR
diagnostic criteria.
Diagnostic and psychopathological assessments made at
baseline and at follow-up were compared, in order to
study the diagnostic stability and the clinical course over
a long term follow up.
Mean age at onset of psychotic symptoms was 26.94
(±6. 73 SD) years. Abuse of more than one drug was
found in 56.4% of the cases. Cannabis resulted as the
most common substance of abuse with a prevalence of
the 85.4% (41 cases) in our sample. Cocaine was used in
18 cases (37.5 %).
Mean duration of follow up was 4.96 years (±3.81 SD,
range 1-15).
At the time of their first admission for psychosis, 25 (52.1%)
and 23 (47,9%) patients were diagnosed as having PPDA
and SIPD, respectively.
Persistence of drug abuse occurred in a similar percentage
of cases amongst baseline diagnoses (52 % and 60.9 %
for PPDA and SIPD groups, respectively).
A shift to Schizophrenia occurred in a similar percentage
of cases: 40.0 % and 34.8% of PPDA and SIPD patients
respectively received a diagnosis of Schizophrenia at
follow-up. Only 4 patients with a baseline diagnosis of
SIPD (17.4%) maintained the diagnosis at follow up.
The two groups were substantially similar regarding
diagnostic stability: a diagnosis of Schizophrenia at
follow-up occurred in a similar percentage of cases. Only
a minority of SIPD patients maintained the diagnosis of
Substance-Induced Psychosis at follow-up.
There was no evidence that SIPD patients had more
tendency to improve their symptomatology after cessation
of drug abuse, compared to PPDA patients.
Up to now, available data regarding the long-term
stability of the distinction between Primary Psychosis with
88
comorbid drug abuse and Substance Induced Psychosis
are insufficient. Despite of the cited-above limitations,
the present results, suggesting that such distinction tends
to vanish over a long-time, are in line with other studies
showing that Substance-Induced Psychotic Disorders
are often followed by development of persistent
psychotic conditions.
Caton CL, Hasin DS, Shrout PE, Drake RE, Dominguez
B, First MB, Samet S, Schanzer B: Stability of early-phase
primary psychotic disorders with concurrent substance use
and substance-induced psychosis. Br J Psychiatry 2007;
190:105-11
Arendt M, Rosenberg R, Foldager L, Perto G, MunkJorgensen P: Cannabis-induced psychosis and subsequent
schizophrenia-spectrum disorders: follow-up study of 535
incident cases. Br J Psychiatry 2005; 187:510-5
Mathias S, Lubman DI, Hides L: Substance-induced
psychosis: a diagnostic conundrum. J Clin Psychiatry
2008; 69(3):358-67
DeLisi LE: The effect of cannabis on the brain: can it
cause brain anomalies that lead to increased risk for
schizophrenia ? Curr Opin Psychiatry 2008; 21: 140-50
P032
Psychosis and abuse of substances in an ambulatory
program of dual pathology
L. Grau-López, C. Barral, C. Roncero, L. Fernández, B.
Gonzalvo, M. Rovira, M. Casas Brugué
Introduction:
Over 50 % of patients with psychiatric disorders have
a substance use disorder (SUD). Moreover, it has been
described that 47% of patients with a diagnosis of
psychosis have a drug addiction. In Spain there are only
a few centres that provide an integral attention to patients
with dual diagnosis (DD) and there are not ambulatory
programs for the treatment of DD patients.
Objective:
To describe the characteristics of patients with psychosis
and SUD in the ambulatory program of dual pathology
of the outpatient drug clinic (CAS Vall d’Hebron) of the
Hospital Universitari Vall d’Hebron (HUVH).
Material and methods:
We included patients with psychotic disorder and SUD who
demanded attention in the CAS HUVH from September,
2007 to September, 2008. The protocol variables of the
study were: demographic data (gender, age, studies
degree, occupation and marital stage), psychiatric
diagnosis using the SCID I and SCID II test, and addiction
of substances.
Results:
Collegium Internationale Neuro-Psychopharmacologicum
Of 69 patients included in program of dual Pathology,
56.5% had psychotic disorder: 17.4% schizophrenia,
24.6% psychotic not specified disorder and 14.5%
esquizofective disorder. Of them the 84% were men. The
mean of age was 35 +/-8 years. Most of patients (79%)
lived with their parents. No patients had high-degree
studies, but 71.8 % had basic studies. Only the 18% had
a job occupation.
The 84.6% of patients with psychotic disorders was
polydrug addicts. The drugs that were more commonly
consumed were cocaine (79.5%), alcohol (69.2%),
cannabis (53%) and heroine (43.6%)
Conclusions:
Patients with psychotic disorder and SUD in our ambulatory
program for dual pathology were mainly men, singles,
with basic studies and without occupation. The principal
substance of consumption in psychotic dual patients was
cocaine.
The patients present high level of psychopathology and
social problems
The knowledge of patients characteristics can help us for
offering a specific treatment.
P033
Polysmonographic Results of Patients with Depression
Before and After Switching from Bupropion Sustained
Release to Bupropion Extended Release
Lauren Lazowski and Roumen Milev. Depratment of
Psychiarty and Centre for Neuroscience, Queen’s
University, Kingston, Canada.
Background:
Bupropion, a norepinephrine and dopamine reuptake
inhibitor, is an effective antidepressant. Frequent side
effects include initial insomnia and reduced sleep
efficiency, especially when taken at night (Thase, 2005).
In Canada, two forms of the compound exist, sustained
release (SR) and extended release (XL). The bupropion
SR formulation cannot be given as more than 150
mg in a single dose, and higher doses are commonly
required for the treatment of depression. A second dose
must be given at least 8 hours later in order to avoid
reaching high plasma concentrations and to reduce
risk of seizures. The twice a day dosing may result
in increased complaints of insomnia, due to a peak
plasma concentration occurring just before sleep, and
have reduced treatment compliance compared to once
daily dosing (Fava et al, 2005). Objectives: Primarily,
to examine the effect of switching patients experiencing
a major depressive episode from bupropion SR to
bupropion XL on sleep efficiency. Secondarily, to compare
objective and subjective sleep quality in these patients
when treated with bupropion XL versus bupropion SR and
to assess the impact of this change on overall treatment
of depression. Methods: 20 patients (12 female, 8 male)
experiencing a major depressive episode who were taking
bupropion SR twice daily were switched to the same dose
of bupropion XL once daily. Polysomnographic, illness
severity and subjective sleep quality measures were taken
before switching, 3-4 and 21-28 days after switching to
the XL formulation (open-label). Results: No significant
changes in total sleep time, sleep efficiency, number of
awakenings, latency to sleep, or respiratory disturbance
index were seen after switching to the XL formulation. As
well, there were no significant changes in subjective sleep
quality, as measured by the Pittsburgh Sleep Quality Index.
However, there was a significant decrease in depressive
symptoms, as measured by the Montgomery Asberg
Depression Rating Scale, from baseline (19.93 ± 2.30 )
to day 21-28 (12.85 ± 1.79 ) and a significant decrease
in daytime somnolence, as measured by the Epworth
Sleepiness Scale, from 8.3 ± 5.7 at baseline to 6.9 ±
4.5 3-4 weeks after switching formulations. Conclusions:
Switching from Bupropion SR twice daily to Bupropion XL
once daily does not significantly alter sleep efficiency or
quality. However, switching from the SR to XL formulation
may have contributed to the significant reduction in
severity of depressive symptoms and daytime sleepiness.
Reference:
1. Thase, M et al. J Clin Psychiatry. 2005; 66: 974-981.
2. Fava, M. et al. Prim Care Companion J Clin
Psychiatry.2005,7:106-113
P034
Cannabis Use and Sub Clinical Psychotic Symptoms:
is Public Mental Health at Risk?
Authors:
Christian D. Schubart, MD MSc 1, Marco P.M. Boks, MD
PhD1, Iris E.C. Sommer, MD PhD1, Elemi J. Breetvelt, MD
MSc 1, Sterre L. Beetz, MSc1, Willemijn van Gastel, MSc1,
Roel A. Ophoff, PhD 1,2, René S. Kahn, MD PhD1.
Affiliations:
1. Rudolf Magnus Institute of Neuroscience, University
Medical Centre Utrecht, Department of Psychiatry,
The Netherlands.
2. University Medical Centre Utrecht, Department of
Medical Genetics, Utrecht, the Netherlands.
Objective of the study:
Cannabis is the most frequently used illicit substance in
most parts of the world. The estimated lifetime cannabis
exposure of the current generation of adolescents in the
Netherlands is about 45%. In Europe the age of onset
of cannabis use is decreasing 1. Since adolescence is a
crucial life stage for social, educational and emotional
development, disruption of this development may have
severe consequences. Numerous large longitudinal
studies and several systematic reviews indicate that
cannabis increases the odds of developing a psychotic
disorder 2. These adverse effects of cannabis use are
most pronounced among those exposed to THC at
young age 3. Until now most studies have focused on
full blown psychotic disorders, and it remains obscured
Major Psychoses and Substance Abuse
89
Poster Abstracts
to what extent cannabis exposure influences the chance
of causing psychotic symptoms that persist beyond
acute intoxication but do not directly lead to a clinical
psychotic disorder according to DSM-IV. However sub
clinical psychotic phenomena may have a strong impact
on mental functioning and general wellbeing and the
widespread use of cannabis among adolescents raises
serious concern about the impact of cannabis on public
mental health. Previous studies addressing the impact of
THC on psychotic symptoms were relatively small and
typically measure cannabis exposure in terms of frequency
of cannabis use or a DSM-IV diagnosis of cannabis
dependency. We here report on a large population
study (N=13.888) on the association between quantity
and initial age of THC exposure and the experience of
psychotic symptoms in the general population.
Reference List:
1. Monshouwer K, Smit F, de GR, van OJ, Vollebergh
W. First cannabis use: does onset shift to younger
ages? Findings from 1988 to 2003 from the Dutch
National School Survey on Substance Use.
Addiction 2005; 100(7):963-970.
Methods:
To asses psychotic symptoms an online version of the
Community Assessment of Psychic Symptoms (CAPE)
questionnaire was used. As a proxy measure of THC
exposure, cannabis use expressed in the amount of euros
(€) consumed per week was used. Initial age of cannabis
use was categorized. In a representative subgroup, the
influence of the use of concomitant drugs was analyzed.
Outcome measures were the odds of belonging to the top
10% incidence and distress of psychotic symptoms and
psychiatric hospitalization in the medical history corrected
for the influence of age, gender, educational level and
use of other drugs.
P035
Summary of Results:
A total of 13.888 respondents participated in this study
(table 1). Using cannabis initially after the age of 15 years
and using less than € 10, - per week, did not increase
the odds of belonging to the 90th percentile of psychotic
symptoms (figure 1 & 2). Participants that used more than
€ 10, - per week showed an association between the
amount of cannabis use and the experience of psychotic
symptoms in a dose dependent manner. Using cannabis
before the age of 12 years was associated with a corrected
odds ratio of 2.13 (95%CI 1.5-3.1). Furthermpre,
this subgroup has an OR of 4.39 (95%CI 2.8-6.8) for
having at least one psychiatric hospitalization in the
medical history.
Conclusions:
The results of this study suggest that regular but moderate
cannabis use and an initial use after the age of 15 years,
is not associated with an increase in the experience of
psychotic symptoms in the general population. However,
starting cannabis use at younger age is strongly associated
with a higher chance of experiencing distressing psychotic
symptoms. Moreover, heavy cannabis use is associated
with a higher prevalence of psychotic symptoms in a dose
dependent manner. Policymakers need to take measures
to protect young adolescents by informing the general
public on the psychiatric risks of cannabis use, especially
in the young.
90
2. Moore TH, Zammit S, Lingford-Hughes A et al.
Cannabis use and risk of psychotic or affective
mental health outcomes: a systematic review.
Lancet 2007; 370(9584):319-328.
3. Konings M, Henquet C, Maharajh HD, Hutchinson
G, van OJ. Early exposure to cannabis and risk
for psychosis in young adolescents in Trinidad.
Acta Psychiatr Scand 2008; 118(3):209-213.
Alexithymia, Hypochondriasis and Obsessive-Compulsive
symptoms in patients with Chronic Prostatitis
Psychiatrists1: Georgios Moussas, Kalliopi Tournikioti,
Panagiota Korkoliakou, Styliani Nika, Christos
Christodoulou, Lefteris Lycouras
Internists2 : Sotiris Tsiodras, Georgios-Michael Gourgoulis,
Periklis Panagopoulos, Styliani Sympardi, Helene
Giamarellou
1
Dept of Psychiatry, Attikon Univerity Hospital,
Athens, Greece
2
4th Dept of Internal Medicine, Attikon Univeristy
Hospital, Athens, Greece
Background:
Chronic prostatitis has been considered a psychosomatic
illness. Nevertheless, the psychological profile of patients
suffering from it, has not been fully elucidated yet. Anxiety
related disorders such as phobic anxiety, somatization
and obsessive-compulsive features have been observed
in men with chronic prostatitis.
Methods:
Patients diagnosed with chronic prostatitis at a tertiary
care ID clinic have been evaluated for the presence of
alexithymia, hypochondriasis and obessive-compulsive
symptoms using the following psychometric tools: Toronto
Alexithymia Scale (TAS-20), Whiteley-Index and LeytonTrait Obsessional Inventory. Patients were categorized
according to the NIH Consensus Classification System for
prostatitis category and the Chronic Prostatitis Symptom
Index (CPSI) was also administered. Association of
psychiatric symptoms with chronic prostatitis has been
performed.
Results:
Forty-five patients have been evaluated so far (mean
age 42, S.D. 11.1) with mean CPSI score 18.3 (S.D.
8.6). Mean Whiteley score was 32.5 (S.D. 8.7), mean
Leyton-Trait score 12.8 (S.D. 3.2), and mean TAS-20 total
score was 46.2 (S.D. 12.1). Abnormal Whiteley score
was noted in 46% of patients whereas abnormal Leyton-
Collegium Internationale Neuro-Psychopharmacologicum
Trait score in 63.1%. Correlation coefficients showed a
significant association between CPSI and TAS-20 total
score (r=0.473, p=0.03), between Whiteley Index score
and TAS-20 total score (r=0.387, p=0.01) and between
Whiteley-Index score and Leyton-trait score (r=0.39,
p=0.01). Increasing age was associated with increased
TAS-20 external orientation of emotions subscale (r=0.44,
p=0.005).
Conclusion:
Chronic prostatitis is frequently associated with
psychopathology, mostly hypochondriasis, obsessivecomplulsive symptoms and alexithymia. Management of
these patients should include psychological and psychiatric
consultation and appropriate therapeutic inteventions.
P039
Correlations between treatment response of aripiprazole
and somnolence : preliminary study
Kyung Hee Jung, M.D.1; Yong Jin Lee, M.D.2; Jeong Min
Song, M.D.2; Sung Doo Won, M.A.1; Yang Weon Bang,
M.D.1; Im Yel Kim, M.D.1
Keyo hospital, Dept of psychiatry, Uiwang-City,
South-Korea 1
Shinae hospital, Dept of psychiatry, Gimchen-City,
South-Korea 2
Object:
Somnolence is a common side effect of atypical
antipsychotics. Sedating medications can be useful in
reducing the acute agitation in the early period of treatment.
However, excessive sedation is considered an unwanted
side effect of treatment for patients with schizophrenia.
Aripiprazole is known as an agent with minimal sedating
properties. However, in our clinical experiences, there
seems to be better clinical improvement in patients who
tended to be sedated in the early period of treatment with
aripiprazole. In order to determine whether appearance
of somnolence in early treatment period with aripiprazole
influences treatment response, the effect of aripiprazole
in acute patients with schizophrenia was examined.
Method:
Patients with a DSM- diagnosis of schizophrenia (N=25:
M=10, F=15; mean age=37.8, SD=12.43) were recruited
to treat with aripiprazole (mean 17.1mg/day, SD=10.35)
for 6 weeks. They were divided into groups experiencing
somnolence(N=6) or non-somnolence(N=19) after the
first week of therapy with aripiprazole 10mg/day at A.M.
Efficacy measures included the Positive and Negative
syndrome Scale (PANSS) total, PANSS positive, PANSS
negative, PANSS general, the Clinical Global Impressions
(CGI)-severity of illness, and the CGI-improvement
scores. Quality of subjective excessive daytime sleepiness
was assessed by the Epworth Sleepiness Scale(ESS). To
examine relations between efficacy and somnolence,
measurements were conducted by correlation analysis
and t-test.
Result:
All subjects were not significantly different in the duration of
illness(t=1.041, p=0.309), admission numbers(t=1.648,
p=0.113), and total duration of admission(t=1.073,
p=0.294). Correlations among the PANSS total, PANSS
positive, PANSS negative, PANSS general scores and
somnolence were positive(r=.666, .670, .517, .690,
respectively). Correlation between the CGI-I scores and
somnolence was negative(r=-.634). In both somnolent
and non-somnolent groups, aripiprazole treatment
produced significantly lower PANSS total scores and CGI
improvement scores from the baseline. The somnolent
group, however, had significantly greater reduction from
the baseline in PANSS total(t=-3.914, p<.001), PANSS
positive(t=-2.99, p=.007), PANSS negative(t=-2.005,
p=.057), PANSS general(t=-4.438, p<.001) scores.
The somnolent group got the lower point than the nonsomnolent group in the CGI-I scores(t=4.261, p<.001).
Conclusion:
Appearances of somnolence in the early period of
treatment were related to efficacy in aripiprazole treatment.
This finding suggests that early onset somnolence
in aripiprazole treatment could be a prediction index
of efficacy.
P040
Prognosis in dual diagnosis
Pablo Martínez-Gómez, María José Duran-Maseda, Silvia
Martínez-Formoso, María Tajes-Alonso, Alfonso MozosAnsorena, Manuela Pérez-García, Julia Portillo Díez,
Mario Páramo- Fernández
Department of Psychiatry. Complejo Hospitalario
Universitario. Santiago de Compostela. Spain.
Background:
Bipolar disorder –BD- associated with substance
misuse disorders –SMD-(so-called dual diagnosis
–DD-) determines a worse prognois, according diverse
epidemiological issuess. In general population the dual
diagnosis in bipolar disorder showes figures of prevalencia
about 61 % in bipolar disorder type I and 48 % in bipolar
disorder type II.
Method:
We made a retrospectively study in a sample of 190
inpatients with diagnosis of bipolar disorder admitted in
acute psychiatric ward between 1998 and 2007. The aim
of this study is to compare two cohorts of patients with
and without dual diagnosis in regarding the number of
psychiatric hospital admissions, number of psychoactive
drugs used in each hospital admission and the time of
average hospital stay.
Major Psychoses and Substance Abuse
91
Poster Abstracts
Results:
The 14´2 % of the patients with bipolar disorder is
associated with substance use disorders in our sample.
This group of patients showed lower time average
hospital stay (21´0251 days vs 24´1494 days, p >
0,05), higher number of psychoactive drugs used in each
hospital admission(4,7241 vs 4,0799,p= 0,005) and
higher number of hospital readmissions (2´30 vs 1´43
,p=0´001).
Conclusions:
The dual diagnosis in bipolar disorder worsens the
prognosis of these patients (regarding the number
of psychiatric hospital admissions and number of
psychoactive drugs used in each hospital admission) an
increase the health bill, according similar issues like this.
P041
Early adolescent exposure to cannabis is associated with
negative symptoms in psychosis
Demjaha A, Di Forti M, Morgan C, Stahl D, Mondelli V,
Marques T, Papparelli A, Prescott C, Luzi S, Russo M, Stilo
S, Wiffen B, Murray R
Objective:
Cannabis use, particularly in early adolescence, is
associated with the risk of developing psychosis. A
number of studies have reported more prominent positive
symptoms, increased thought disturbance, but fewer
negative symptoms in those who use cannabis. It is unclear,
however, whether psychopathology differs in those who
commenced cannabis use in early adolescence. We
examined the association of cannabis use with different
symptom profiles in a first onset psychosis sample and
explored whether early cannabis users are symptomatically
distinct from their older counterparts.
Method:
Positive and Negative Symptom Scale (PANSS) was
used to assess psychopathology of 93 patients who
had presented to specialist mental health services with
a first episode of psychosis. The relationship between
positive, negative and general psychopathology PANNS
scores, and lifetime cannabis use was examined,
employing t test statistics. The symptom scores were then
compared between those who used cannabis before and
after age 16.
Results:
Lifetime cannabis use was significantly associated with
higher scores of positive symptoms (p=0.008). With
regards to the age of cannabis use, early users tended
to have more negative (but not positive) symptoms when
compared to those who started using cannabis after age
16 (p= 0.015).
92
Conclusion:
Our preliminary data indicate that early adolescence
exposure to cannabis may be associated with more
prominent negative symptoms; adolescence could be
a sensitive period of neurobiological vulnerability to
cannabis.
P042
Influence of cannabis use in plasma leptin levels in a drug
naive sample of first episodes of psychosis.
Moreno-Calle T, Perez-Iglesias R, Martinez-Garcia O,
Vazquez-Barquero JL, Crespo-Facorro B.
Introduction:
There are several studies reflecting the influence of
antipsychotic treatment on the alteration of leptin plasma
levels. There is also evidence for a role of leptin in
regulating endocannabinoid synthyesis and activation of
CB1 receptors and its effects in appetite regulation.
Aim of the study:
To explore the effect of cannabis use in plasma leptin levels
in a drug naïve sample of first episodes of psychosis.
Materials and methods:
A cross-sectional study was conducted in a sample of non
affective psychosis referred to a first episode program in
the region of Cantabria (Spain). The sample was formed
by 174 patients (66 females and 108 males) accepted
in the program from 2001 to 2005, fulfilling the next
inclusion criteria: patients aged 15–60; meeting DSMIV criteria for a principal diagnosis of a non-affective
psychosis; living in the catchment area; no prior treatment
with antipsychotic medication or, if previously treated, a
total life time of adequate antipsychotic treatment of less
than 6 weeks; current psychotic symptoms of moderate
severity or greater assessed by one of the five items of
the Scale for the assessment of positive symptoms (SAPS).
The exclusion criteria were mental retardation and
fulfilling DSM IV criteria for drug dependence. Written
consent was obtained from the participants. Clinical,
analytical and socidemographical data were obtained at
baseline, including cannabis use, as well as fasting leptin
plasma levels. Data analysis was performed with SPSS
14.0. Separate analysis were conducted both in males
and females according to gender differences in normal
leptin levels and sex-dependant alterations in drug naïve
first episodes of psychosis leptin plasma levels suggested
by previous research. Relationship between cannabis
use and continuous variables with normal distribution
was assessed with Student T, whereas with non-normal
distributed variables Mann Whitney test was performed.
A univariate analysis was conducted covariating by other
significant variables that could be acting as confusing
factors such as bmi and age.
Collegium Internationale Neuro-Psychopharmacologicum
Results:
Among females 21.2% (14) were cannabis smokers. Leptin
levels in non smokers were higher than in the smoker
group (mean of 13.53+-9.51 vs 7.65+-3.06), although
it didn’t reach statistical signification. After covariating by
age and bmi as likely confounding factors it remained
statistically unsignificant ( mean 13.40+-9.69 vs 7.65+3.06; p 0.3).
In males, 63.0% (68) were cannabis users. Leptin levels
were found to be higher in non cannabis user group
compared to cannabis users (mean 6.95+-6.58 vs
3.16+-2.78; p<0.0001). This difference remained
significant after covariating by age and bmi, that could
be acting as confounding factors (mean 7.39+-6.85 vs
3.18+-2.81; p 0.008).
Discussion:
Cannabis use was found to decrease leptin levels in our
male sample even after covariating for possible confusion
factors. This could be altering the effects of leptin levels
in regulating the endocannabinoid concentration in
the hypothalamus. Among the female sample the data
followed the same trend, but didn’t reach statistical
signification, probably due to the smaller sample size.
Further research is needed to clarify this issue and its
stability in a longitudinal follow up.
P043
Cannabis, age of onset and clinical presentation in the
early phases of bipolar disorder.
Moreno-Calle T, Mayoral-vanSon J, Caballero P, Gomez
E, Higuera A, Villacorta C, Vazquez-Barquero JL, ArtalSimon J.
Introduction:
Cannabis is the most commonly abused drug among
individuals with bipolar disorder. Cannabis use is known
to worsen the prognosis of different mental disorders,
including bipolar disorder. Few studies have attempted
to study the influence of cannabis use in the clinical
characteristics in the early phases of bipolar disorder.
Aims of the study:
To explore the relationship between cannabis use, age of
onset and clinical presentation in a sample of subjects in
early phases of bipolar disorder.
Materials and methods:
A cross sectional study was conducted in a sample of
bipolar disorder patients in the early phases of the disorder
from the Early Phases of Bipolar Disorder Program
(JANO) of Cantabria, Spain, a region of about half a
million inhabitants. The inclusion criteria of the program
were fulfilling DSM IV criteria for Bipolar Disorder, type I
or II, being less than ten years since the first depressive
episode, less than five years since the first manic episode
and being able to sign an informed consent. The
exclusion criteria were having a severe comorbid organic
disease, dementia, mental retardation and substance
dependence. Clinical and sociodemographical variables
were studied in our sample. Primary outcome was the
relationship between cannabis use and age of diagnosis
of bipolar disorder, and the secondary outcome was
to describe the influence of cannabis use in clinical
presentation of bipolar disorder. Statistical analysis was
performed with SPSS 14.0. Chi square was used with
dychotomic variables and to test the relationship between
cannabis use and continuous variables Mann Whitney test
was performed.
Results:
43 patients fulfilled the inclusion criteria. 7 of them
(16.3%) were cannabis users. There were no differences
in sex distribution of cannabis user group and the nonuser group. Age of diagnosis of bipolar disorder was
significantly younger among the cannabis user group
( 26.31+-6.31 vs 36.06+-11.1; p 0.005). There were no
differences in the total number of episodes, the number
of manic, depressive or mixed episodes, the number
of hospitalizations or the rate of family history of
bipolar disorder.
Conclusions:
Cannabis users were diagnosed in earlier ages when
compared to cannabis non-users. This study design does
not allow us to understand the direction of this relationship,
could it be a reflection of self medication in more severe
patients or cannabis could be precipitating the onset of
the disorder. However the similarity in the number of
episodes, the rate of hospitalization and the family history
in both groups suggests that the later explanation is more
likely to be happening. Further research is needed in
this area.
P044
Cigarette smoking is associated with depression and
suicide idea in patients with schizophrenia
Jin-Sang Yoon,1 Sung-Wan Kim,1 Jae-Min Kim,1 and
Suelin Yoon.2
1
Department of Psychiatry, Chonnam National University
Medical School, Gwangju, Republic of Korea
2
Psychiatry Research, IOP, King’s College, London, UK
Objective:
Cigarette smoking is prevalent in patients with
schizophrenia. This study was aimed to determine
the characteristics of schizophrenia patients with
cigarette smoking.
Method:
A total of one hundred and forty five patients with
schizophrenia were participated in this study. Patients with
six scores or higher in Fagerstrom Nicotine Dependence
Scale were classified as heavy smoker. The Positive and
Negative Syndrome Scale, Social and Occupational
Functioning Assessment Scale, Calgary Depression Scale
Major Psychoses and Substance Abuse
93
Poster Abstracts
for Schizophrenia (CDSS), Subjective Wellbeing under
Neuroleptics Scale, Beck Depression Inventory, Simpson–
Angus Scale, Barnes Akathisia Scale, and Abnormal
Involuntary Movement scale were administrated.
and cocaine dependence comorbidity. Evolution was
described by means of Kaplan-Meier method. One CoxRegression prediction model (Forward method, Likelihood
Ratio, PIN 0.05, POUT 0.10) was tested.
Results:
Twenty seven patients (18.5%) were classified as heavy
smoker and thirty seven patients (25.3%) were light smoker.
CDSS score was significantly higher in patients with heavy
smoker than in those with non-smoker and light smoker
(p=0.008). Suicide idea was also significantly more
frequent in patients with heavy smoker (55.6%) compared
to patients with non-smoker and light smoker (30.5% and
27.0%, respectively; p=0.033). Other psychopathology
and extrapyramidal side effects were not significantly
different according to the smoking status.
Results:
Treatment was maintained during one mean time of
10.30 mounts (SD: 15.8). Treatment was suppressed
due to remission in 13 cases (12.1%), due to insufficient
response or intolerance in 19 cases (17.8%), and 69
patients (64.5%) maintain treatment at the end of the
follow-up. Median time to relapse was 7.7 mounts (95%
CI 5.4 to 10.0). None of the predictors were included
in the model, suggesting that they do not modify the
therapeutic effect of naltrexone.
Conclusions:
Cigarette smoking is associated with depression and
suicide idea in patients with schizophrenia. Longitudinal
study is warranted to find out the causal relationship
among smoking, depression, and suicide idea.
P045
Effectiveness of naltrexone in the treatment of alcohol
dependence: longitudinal study of clinical predictors.
Vargas ML, Bermejo A, Boizas J, Del Brio AM, Fernandez
ML, Franco MA.
Addictive Behaviour Unit. Psychiatric Service. Complejo
Asistencial de Zamora. Spain.
Correspondence: [email protected]
Aims:
The opiate receptor antagonist naltrexone is one effective
treatment indicated in the treatment of alcohol dependence.
It acts mainly by reducing alcohol craving and alcohol
reward. A short-term treatment of naltrexone significantly
decreases the relapse in alcohol consumption with one
Risk Ratio of 0.64 (1). The aim of this study is to know if
the effectiveness of the treatment with naltrexone depends
on clinical factors that could modify the therapeutic effect
in real clinical conditions.
Method:
It was conducted one observational study analyzing clinical
predictive factors of the effectiveness of naltrexone (50
mg/day) in the treatment of alcohol dependence. It was
retrospectively studied one sample of 107 out-patients
(88 male -82.2 %-; 19 female -17.8 %-) with alcohol
dependence. The mean age when starting treatment was
41.7 years (SD: 9.8). Seventy-eight patients (72.9 %) did
not have any other dependence, while 29 patients (27.1
%) had comorbid cocaine dependence. There not exists
dual pathology in 55 patients (51.4 %), but 17 (15.9 %)
had any personality disorder, 15 (14.0 %) had affective
disorders, 12 (11.2 %) had any psychotic disorder and
6 (5.6 %) had any other dual diagnosis. As effectiveness
variable it was used the time to first relapse in alcohol
consume after treatment beginning. There were studied
four putative clinical predictors: sex, age, dual diagnosis
94
Conclusion:
The effectiveness of naltrexone in the treatment of alcohol
dependence do not depend on the effect of sex, age, dual
diagnosis nor cocaine dependence comorbidity.
1.Srisurapanont M, Jarusuraisin N. Opioid antagonists
for alcohol dependence. Cochrane Database Syst Rev
2005(1):CD001867.
P046
Cannabis use in first psychotic episode: differences in
premorbid adjustment and early symptoms.
A.Barajas1, I.Baños1, E.Huerta1, A.Miñambres1, M.Pardo2,
M.Planella1, J.Usall1, B.Sánchez2, M.Dolz2, S.Ochoa1.
1.
Unidad de Investigación, Sant Joan de Déu-SSM
(Barcelona, Spain). Fundació Sant Joan de Déu.
2.
Hospital de Sant Joan de Déu (Barcelona, Spain).
Introduction:
Nowadays, there is an increasing interest in the role of
cannabis use in first psychotic episode. Prevalence rates
of cannabis use in this population is 86%(Edwards et al.
2006). Arndt et al. (1992) showed that psychotic patients
who use cannabis had better premorbid adjustment than
those who do not use cannabis.
General objective:
To compare different cannabis’ consumers groups vs.
non-consumers, in a sample of people who suffer a first
psychotic episode, in relation to premorbid adjustment
and early psychotic symptoms.
Methods:
Longitudinal study of 53 consecutive cases with a
first psychotic episode. Inclusion criteria: two or more
psychotic symptoms; age between 12 to 45 years old; first
consultation to the medical center of study; less than 6
months since the first contact with the medical service; and
less than a year of symptoms’ evolution. The assessment
methodology includes: sociodemographic questionnaire,
PANSS and PAS. One-way ANOVAs were used to compare
different cannabis’ consumers groups vs. non-consumers
on symptoms and premorbid functioning. Bonferroni
corrections were applied for ANOVAs (SPPS 12.0).
Collegium Internationale Neuro-Psychopharmacologicum
Results:
In our sample, 66.7% were male and 52,8% were aged
less than 18. 60,4% of the people in the sample consume
cannabis, and within this group 68.8% consume cannabis
on a dayly basis. Significant differences are obtained
between group of cannabis consumers (everyday users)
( =0,15) vs. non-consumers ( =0,36) in premorbid
social adjustment (p=0,005). Likewise, significant
differences are obtained for the social dimension in each
stage of the individual vital cycle (Childhood: consumers
=0,14 vs. non-consumers
=0,35; p=0,028) (Early
adolescence: consumers
=0,12 vs. non-consumers
=0,35; p=0,002) (Late adolescence: consumers =0,22
vs. non-consumers =0,41; p=0,062).
In the same way, after comparing the group of consumers
(everyday consumers and occasional consumers) with
the group of non-consumers a tendency towards the
significance is also observed in positive dimension of
the PANSS (consumers =25,14 vs. non-consumers
=21,10; p=0,063). No other differences are observed
in relation to PANNS scores.
Conclusion:
In our sample, patients who consume cannabis have a
better social premorbid adjustment than those who don´t
consume cannabis. These differences are observed in
all the stages of the vital cycle (childhood, early and late
adolescence. Patients who consume cannabis exhibit
stronger positive symptomatology at the beginning of the
episode. This result suggests a more violent beginning
of the psychotic episode in the case of the patients who
consume cannabis. In addition to this, these results seem
to suggest that patients who have a first psychotic episode
and who consume cannabis show better premorbid social
functioning than patients who don’t consumer cannabis.
These results could indicate a greater ability to get the
substance in consumers group.
Keywords:
cannabis; first episode; psychosis; adjustment premorbid;
symptomatology.
References:
Arndt, S., Tyrrell, G., Flaum, M., Andreasen, N.C..
Comorbidity substance abuse and schizophrenia: the
role of pre-morbid adjustment. Psychological Medicine,
1992. 22(2): 379-388.
Edwards, J., Elkins, K., Hinton, M., Harrigan, S.M.,
Donovan, K., Athanesopoulos, O., McGorry, P.D.
Randomized controlled trial of a cannabis-focused
intervention for young people with first-episode psicosis.
Acta Psychiatrica Scandinavica, 2006. 114(2): 109-117.
This study was supported by Spanish Ministry of
Health: Fondo de Investigaciones Sanitarias of Spain
(FIS PI05/1115); Instituto Carlos III of Spain, Centro
de INVESTIGACIÓN BIOMÉDICA EN RED DE SALUD
MENTAL CIBERSAM and Fundación Caja Navarra.
P047
Association study of cocaine- and amphetamine-regulated
transcript and schizophrenia
Renan P. Souzaa, Jeffrey A. Liebermanb, Herbert Y. Meltzerc,
James L. Kennedya
a
Neurogenetics Section, CAMH, Toronto, ON, CANADA;
b
Department of Psychiatry, Columbia University, NY, USA;
c
Departments of Psychiatry and Pharmacology, Vanderbilt
University, Nashville, TN, USA.
Cocaine- and amphetamine-regulated transcript (CART)
peptide is a neuropeptide involved in feeding, drug
reward, and stress. A previous report have failed to find
any association among rs2239670 and schizophrenia
in a Korean population. We hypothesized that the
polymorphism of CART gene might be related with
susceptibility to schizophrenia. We examined six CART
variants (rs10515114, rs10515115, rs10515116,
rs3846658, rs3857384, rs7731997) in 220 matched
case-control subjects according to DSM-IV criteria. Our
results have shown no allelic or genotypic association
among any of these six CART variants and schizophrenia
in our sample. Studies in larger and independent samples
are needed to confirm our findings.
P048
DARPP-32 expression in rat brain after electroconvulsive
stimulation
Daniela V. F. Rosa1, Renan P. Souza1, Alexandre G. Barros,1,
Fabrício F. Lima,1, Gustavo Feier2, João Quevedo2 and
Marco A. Romano-Silva1
1
Departamento de Saúde Mental, Universidade Federal
de Minas Gerais, Av Alfredo Balena,190, Belo Horizonte
30130-100 Minas Gerais, Brazil;
2
Laboratorio de Neurociências, Programa de Pós Graduação em Ciências da Saúde, Universidade do
Extremo Sul Catarinense, 88806-000 Criciúma, SC,
Brazil. Financial support: CNPq, CAPES and FAPEMIG
Induction of seizures in the form of electroconvulsive
therapy (ECT) has been used in the treatment of
psychiatric disorders for more than 60 years. Particularly
in the treatment of severe major depression, evidence
for the effectiveness and superiority of ECT over other
treatments is clear and convincing, but little progress has
been made in the mechanisms underlying its therapeutic
or adverse effects. The aim of this work was to analyze
the expression of DARPP-32 (a protein with a central
role in dopaminergic signaling) and pDARPP-32 Thr34
in striatum and prefrontal cortex (PFC) of Wistar rats
subjected to acute or chronic electroconvulsive stimulation
(ECS). Rats were submitted to a single stimulation (acute)
or to a series of eight stimulations, applied one every
48 hours (chronic). Animals were killed for collection of
tissue samples at time zero, 0.5, 3, 12, 24, and 48 hours
after stimulation in the acute model and at the same time
intervals after the last stimulation in the chronic model.
Immunoblot was used to analyze protein expression.
Major Psychoses and Substance Abuse
95
Poster Abstracts
DARPP-32 is a cytosolic protein that is selectively enriched
in medium spiny neurons in the neostriatum. When
DARPP-32 is phosphorylated by cAMP-dependent protein
kinase (PKA) on Thr34, it is converted into a potent
inhibitor of protein phosphatase-1(PP-1). DARPP-32
Thr34 phosphorylation leads to an increase in the state of
phosphorylation of downstream PP1 substrates, including
several neurotransmitter receptors and voltage-gated ion
channels. Our results indicated that acute ECS does not
produces changes in the expression of DARPP-32 neither
pDARPP-32 Thr34 but, interestingly, chronic ECS increased
expression of DARPP-32 and pDARPP-32 Thr34 in several
time frames, in striatum and PFC, after last stimulation.
Results on expression of proteins involved in signaling
pathways are relevant for neuropsychiatric disorders and
treatment, in particular ECT and can contribute to shed
light on the mechanisms related to its mechanism.
P050
Quetiapine Monotherapy in Chronic Posttraumatic
Stress Disorder: A Randomized, Double-Blind, PlaceboControlled Trial
Jose Canive, M.D., Mark Hamner, M.D., Lawrence A.
Calais, R.N., C.C.R.C., Sophie Robert Pharm.D., Gerardo
Villarreal, M.D., Valerie Durkalski, Ph.D., Yusheng Zhai,
M.S.P.H.
Background:
Antidepressants are mainstay treatments for PTSD.
Atypical antipsychotics also may be effective in reducing
symptoms of PTSD in patients who are refractory to
other treatments.
This study investigated the efficacy of monotherapy
with quetiapine, an atypical antipsychotic, in patients
with chronic PTSD.
Method:
A double-blind, randomized, placebo-controlled trial
was conducted. There was a one week placebo phase
followed by a twelve week randomized phase. Eighty
patients entered the study and 77 had as least one
efficacy assessment. The primary outcome measure was
the Clinician-Administered PTSD Scale (CAPS). A number
of secondary rating instruments were also administered
including the Positive and Negative Symptom Scale
(PANSS), Clinical Global Impressions -Severity of Illness
Scale (CGI-S), the CGI-Improvement Scale (CGI-I), the
Hamilton Rating Scale for Depression (HRSD), the Hamilton
rating Scale for Anxiety (HRSA) and other psychosocial and
safety measures. Results: There was a significant decline
in CAPS composite scores in quetiapine-treated patients
as compared with placebo (intent-to-treat analysis, last
observation carried forward, p=0.0070, 2-tailed) and on
re-experiencing (p=0.0019) and hyperarousal symptom
(p=0.030) subscales but not on the avoidance subscale
(p=0.56). Greater improvement was observed in the
CGI-S (p=0.0030), the CGI-I (p=0.030) and the PANSS
composite scores (p=0.0135). The HRSA (p= 0.020) and
HDRS (p=0.0093) also declined with active medication.
96
The average dose of quetiapine was 258 mg daily (range:
50 to 800 mg daily).
Conclusion:
These results suggest that quetiapine monotherapy is
efficacious in the treatment of PTSD. Larger controlled
trials are needed to better define the role of quetiapine
and other atypical antipsychotics alone or as adjuncts in
treating patients suffering from PTSD.
Educational Objectives:
At the conclusion of this session, the participant should
be able to to review mainstay treatments for PTSD,
review literature regarding atypical antipsychotics in this
population, and discuss the results of this controlled trial
of quetiapine in PTSD.
Literature references:
Hamner MB, Deitsch SE, Brodrick PS, Ulmer HG,
Lorberbaum JP: Quetiapine treatment in patients with
posttraumatic stress disorder: an open trial of adjunctive
therapy. J Clin Psychopharmacology 2003: 23(1):
15-20.
Hamner MB, Robert S: Emerging roles for atypical
antipsychotics in chronic posttraumatic stress disorder.
Expert Rev Neurotherapeutics 2005: 5(2):267-75.
PO51
CLINICAL AND PSYCHO-SOCIAL CO-RELATES OF
SUBSTANCE DEPENDENCE IN PSYCHOSIS: PERCEIVED
REASONS AND CONSEQUENCES
1. Sahoo Saddichha *, BA MBBS DPM
National Partner,
Division of Clinical Research,
Emergency Management and Research Institute,
Hyderabad, India
E-mail: [email protected]
Ph: +919000013816 2. Ravi Prakash, MBBS DPM
Resident in Psychiatry,
Central Institute of Psychiatry,
Ranchi, India
3. Baxi Neeraj Prasad Sinha, DPM, MD, DNB
Crisis Resolution and Home Treatment,
University Hospital of North Tees,
Cleveland, UK.
4. Christoday Raja Jayant Khess, MD
Professor and Head of Addiction Psychiatry,
Central Institute of Psychiatry,
Ranchi, India
* Corresponding author.
Background:
Substance use is a common co-morbidity with psychotic
illnesses. Several theories exist to explain this link, but
with evidence existing for all, it is difficult to delineate the
exact link. This study aimed to evaluate the reasons and
consequences for substance use in patients with psychosis
and compare it with an age, sex and tobacco-use matched
Collegium Internationale Neuro-Psychopharmacologicum
control sample without psychosis.
Method: Consecutively admitted patients were divided
into two groups, substance dependence without psychosis
(SD) (n=32) admitted in our Addiction Unit, and psychotic
illness with substance dependence admitted in our
Inpatient Psychosis Unit, called dual-diagnosis group
(DD) (n=62), and administered SCAN for diagnoses as
well as asked open ended questions to evaluate reasons
and consequences for substance use.
Results and discussion: There were significant differences
in reasons for maintenance and relapse of both cannabis
and alcohol, the two most common substances, between
the two groups. While the SD group (56% & 78%
respectively) attributed both maintenance and relapse to
external factors such as nature of work, social milieu or
peer pressure, the DD group (82% & 89% respectively)
attributed them to internal factors such as enhancement
of positive mood and withdrawal (p<0.05).
Conclusion: An inner vulnerability seems to exist for
individuals with psychosis rendering them susceptible
to the possible precipitating effects of cannabis and/or
alcohol. Targeting perceived internal factors may play
a useful role in management and possibly identification
and prevention of psychosis in vulnerable individuals in
the future.
Clinical Implications:
• Substance maintenance in psychosis to cope with
negative moods, to feel energetic or feel good, and
to reduce withdrawal or to get high.
• Course and pattern of dependence differs between
patients with and without psychosis, with the former
being especially vulnerable to the neuro-modulating
effects of cannabis and alcohol.
• Testing the beliefs provided by patients for using
substances or providing individuals with alternative
ways to achieve these effects can be an important
component of treatment.
Limitations:
• Relatively small sample size may limit generalizability
of our findings.
• Open ended interview technique may have attracted
some bias in answering the questions.
• Possibility of recall bias.
Key Words:
Substance
dependence;
Psychosis;
Reasons;
Consequences; Clinical and psycho-social correlates.
P052
Next-Generation GRII Antagonist Prevents and Reverses
Antipsychotic-Induced Weight Gain
Coleman Gross, Robert Roe, Christine Blasey, Joseph
Belanoff
Affiliation: Corcept Therapeutics
Background:
Previous animal studies demonstrated that mifepristone,
a glucocotricoid antagonist and progesterone receptor,
can reverse and prevent olanzapine-induced weight
gain (Beebe, 2006). Rats administered mifepristone also
had less abdominal fat compared with rats taking only
olanzapine.
The goal of the current pair of animal studies was to
investigate the ability of CORT 108297, a newly-identified
selective glucocorticoid antagonist (no progesterone
activity), to both reduce and prevent olanzapineassociated weight gain.
Method:
Reduction of Olanzapine-Induced Weight Gain. In this
56 day experiment, rats (n=72) were allowed to eat a
normal diet. For the first 35 days, 12 rats received vehicle
and 60 rats received olanzapine. Then, these 60 animals
were randomized to receive additionally, for 21 days,
one of the following: vehicle, olanzapine, CORT-108297
(20mg/k), CORT-108297 (60mg/k), CORT-108297
(120mg/k), or mifepistone (60mg/k).
Prevention of Olanzapine-Induced Weight Gain. In
this 21 day experiment, a group of naive rats (n=72)
were randomized to one of the six conditions: vehicle,
olanzapine only, olanzapine plus CORT-108297
(20mg/k), olanzapine plus CORT-108297 (60mg/k),
olanzapine plus CORT-108297 (120mg/k), or olanzapine
plus mifepistone (60mg/k).
In both experiments, weight and food consumption
were measured every two days, and abdominal fat was
measured at study end.
Results:
In experiment 1, rats assigned to olanzapine only gained
significant weight throughout the study. Rats who received
adjunctive 108297 after day 35 subsequently lost
significant weight; and, the amount of weight loss was
linearly related to dose of 108297. Rats administered
108297 plus olanzapine had significantly less abdominal
fat than rats assigned to only olanzapine.
In experiment 2, rats who took olanzapine plus 108297
gained significantly less weight than rats receiving only
olanzapine.
Conclusion:
CORT 108297, a pure glucocorticoid antagonist appears
to have the potential to block the weight gain caused by
atypical antipsychotics. Eventually, this novel compound
may be tested in clinical trials with humans.
Major Psychoses and Substance Abuse
97
Poster Abstracts
P053
Mifepristone Reduces Weight Gain Associated with
Risperidone Use
Coleman Gross1, Christine Blasey2, Karen Hafez1, Joseph
Belanoff1
Affiliations: 1Corcept Therapeutics, 2Corcept Therapeutics
and Stanford University
Objective:
The purpose of this study was to evaluate the efficacy
of mifepristone, a glucocorticoid antagonist, for the
prevention of antipsychotic-induced weight gain. Our
previous randomized controlled trials demonstrated
that mifepristone significantly mitigated the weight gain
associated with olanzapine, an antipsychotic known for
deleterious side effects including weight and metabolic
changes. The current study tested the role of mifepristone in
the mitigation of weight gain due to another antipsychotic:
risperidone. Like olanzapine, risperidone use has also
been associated with weight changes, although to a
lesser extent.
Methods:
Healthy, Indian males (BMI>18 and <23 kg/m2) were
enrolled in a three-arm randomized clinical trial conducted
in an institutional setting. Participants were randomized to
receive either risperidone plus placebo, risperidone plus
mifepristone, or mifepristone plus placebo. Participants
were dosed daily for 28 days. The primary endpoint was
the change in weight from baseline to day 28. Secondary
endpoints included changes in food intake, abdominal
fat, and waist circumference.
Results:
Analyses of covariance indicated that the group receiving
risperidone plus placebo gained significantly more
weight compared with the group receiving risperidone
plus mifepristone (p<.01). Groups differences were also
observed on several secondary endpoints.
Conclusions:
Preliminary results indicate that participants taking
risperidone gained significant weight in a short period
of time. However, participants taking mifepristone in
conjunction with risperidone gained significantly less
weight and had less abdominal fat. The potential for
mifepristone to reduce the substantial health risks
associated with antipsychotic use is discussed.
P054
Smoking patterns and motives in early psychosis patients:
a matched control study
Sherry H. Stewart,1,2 Heather G. Fulton,2 Sean P. Barrett,2,1
Kimberley Good,1,2,3 Ron Leslie,4 Alissa Pencer,5,1,2 David
Whitehorn,3 & Heather Milliken1,3
1
Department of Psychiatry, Dalhousie University, Halifax,
Nova Scotia, Canada
2
Department of Psychology, Dalhousie University, Halifax,
Nova Scotia, Canada
3
Nova Scotia Early Psychosis Program, Halifax,
Nova Scotia, Canada
4
Department of Pharmacology, Dalhousie University,
Halifax, Nova Scotia, Canada
5
Izzak Walton Killam Health Centre, Halifax,
Nova Scotia Canada
Smoking rates are extremely elevated among individuals
with psychosis both in comparison to individuals with other
psychiatric disorders and, particularly, in comparison to
individuals from the general population. However, little
research has examined how and why individuals with
psychosis use tobacco. Moreover, few studies have made
direct comparisons of psychosis patients who smoke to
smoking controls without psychosis. In the present study,
sections of the Addiction Severity Index (McLellan et al.,
1985), the Fagerstrom Test for Nicotine Dependence
(Heatherton et al., 1991), the Time Line Follow Back
method (Sobell & Sobell, 1992), and the Reasons for
Smoking test (Ikard et al., 1969) were used to assess
early psychosis patients’ patterns of current and lifetime
tobacco use, and their motives for smoking, in comparison
to age- and gender-matched controls without psychosis.
Smokers with psychosis smoked more cigarettes per
day (p < .01), and were less likely to use tobacco with
other substances like cannabis or alcohol (p < .05), than
control smokers. Smokers with psychosis also reported
greater tobacco dependence levels on the Fagerstrom (p
< .01). In regression analyses, patient status predicted
tobacco dependence levels over and above other
variables (e.g., previous substance use; R2 change=.34,
p < .05). Smokers with psychosis also scored significantly
higher on the Addiction/Craving scale of the Reasons for
Smoking test than current smoker controls (p < .01). No
differences between these two groups were found on the
other smoking motives scales of the Reasons for Smoking
test. Results provide insight into how and why patients with
psychosis use tobacco, and suggest ways that we might
tailor cessation programs to better serve this population.
Note:
This study was funded through grants from the Dalhousie
University Department of Psychiatry Research Fund,
and the Canadian Tobacco Control Research Initiative
Interdisciplinary Capacity Enhancement program.
98
Collegium Internationale Neuro-Psychopharmacologicum
P055
Background:
Combat related Post Traumatic Stress Disorder (PTSD) is a
serious, disabling condition which often fails to respond to
pharmacotherapy. Although Tiagabine has demonstrated
some benefit in civilian PTSD, there are no studies
investigating its effectiveness in war related trauma.
Objective:
To investigate the effects of Tiagabine given as
monotherapy in Vietnam combat veterans with PTSD.
Methods:
Seven Vietnam veterans diagnosed with PTSD were
randomly assigned Tiagabine or matching placebo as
part of a multicenter study on the effects of Tiagabine
in Post Traumatic Stress Disorder. Subjects were treated
for twelve weeks with flexible doses of Tiagabine or
placebo up to 16 mg per day followed by 12 months
of open label Tiagabine for those consenting to continue
the study. Symptom severity was evaluated using
the Clinician Administered Post Traumatic Stress Test
(CAPSS), the Treatment Outcome PTSD Scale (TOP-8),
the Davidson Trauma Scale (DTS), the Connor Davidson
Resilience Scale (CD-RISC), as well as the Clinical
Global Impression Severity (CGI-S) and Clinical Global
Impression Improvement (CGI-I) ratings administered at
weeks 2, 4, 8, and 12 during double-blind treatment and
monthly during open-label therapy.
Results:
Subjects were markedly ill prior to randomization (mean
CGI-S=5.0). Following 12 weeks double-blind treatment,
mean total CAPSS scores decreased from 86.7 to 66.0
in the active treatment group and from 73.8 to 69.0 in
placebo treated subjects. Two of the three subjects on
active medication and one of the four on placebo were
rated “much improved” or “very much improved” on the
CGI-I. Open-label treatment with Tiagabine for months
resulted in a decrease in mean total CAPSS scores from
77.0 at open label baseline compared to 65.5 at end
of treatment. Of the four subjects involved in the openlabel phase, three were judged “much improved” while
the fourth subject showed no benefit. Less than a 10%
difference between Tiagabine treated subjects and
placebo was obtained on other rating scales. Nausea and
sedation were the most common adverse events during
up-titration however no subject withdrew from the study
due to side effects.
Conclusions:
These preliminary results from a small post hoc subgroup
of Vietnam combat veterans suggest that monotherapy
with Tiagabine may benefit symptoms of combat
related PTSD. Larger sample sizes are needed to verify
these findings.
P056
Clinical characteristics of obsessive compulsive disorder
with schizophrenia
Min-Seong Koo, M.D.1, Ho Suk Suh, M.D.2, Chan-Hyung
Kim, M.D 3
1
Department of Psychiatry, College of Medicine,
Kwandong University
2
Department of Psychiatry, Pocheon Cha University,
3
Department of Psychiatry, College of Medicine, Yonsei University, Seoul, Korea,
Objectives:
We investigated the prevalence of obsessive compulsive
disorder (OCD) among patients with schizophrenia. We
also investigated the differences in the psychotic symptoms
and suicidality between patients with schizophrenia who
did or did not have OC symptoms.
Method:
Seventy-one subjects with the DSM-IV diagnosis of
schizophrenia were evaluated by the Structured Clinical
Interview for DSM-IV Axis I disorders, the Yale-Brown
Obsessive-compulsive Scale and the Positive and Negative
Syndrome Scale.
Results:
The OCD patients with schizophrenia were 20 (28.2%)
among 71 subjects. The 20 subjects with OCD had
significantly more severe negative and total psychotic
symptoms evaluated with PANSS than subjects without
OCD. The schizophrenia with OCD had significant higher
recent suicidal attempt rate than the subjects without
OCD.
Conclusions:
The results of this study suggest the possibility that OCD
symptoms in schizophrenia may be related to negative
symptoms and the OC symptoms may be related to the
impulsivity expressed as suicidal attempts.
Key words: Obsessive compulsive disorder • Schizophrenia
• Clinical characteristic.
P057
Clinical Predictors of Drug Response in Patients with
Obsessive-Compulsive Disorder
Min-Seong Koo, M.D. 1, Chan-Hyung Kim, M.D.2, Ho Suk
Suh, M.D. 3
1
Department of Psychiatry, College of Medicine,
Kwandong University
2
Department of Psychiatry, College of Medicine,
Yonsei University,
3
Department of Psychiatry, Pocheon Cha University,
Seoul, Korea
Objective:
The aim of this study was to evaluate which clinical
variables might influence the antiobsessional response
to proserotonergic drugs in a sample of patients with
Major Psychoses and Substance Abuse
99
Poster Abstracts
obsessive-compulsive disorder(OCD). Methods: Two
hundred forthy-nine patients with DSM-IV OCD underwent
mean 13-month treatment with selective serotonin reuptake
inhibitors. According to treatment response, defined as a
reduction of the Yale-Brown Obsessive Compulsive Scale
total score >35% and CGI 1 or 2, patients were divided
into two groups. Results: One hundred fourteen patients
responded to treatment and one hundred thirty five
patients did not. Responders had a significant high long
duration of treatment, short duration of pre-treatment
medication and higher frequency of drug naïve cases
and lower baseline Y-BOCS scores. Conclusion: The pretreatment factors including pre-treatment period, drug
naïve or not and baseline OCD symptoms and the factor
of duration of treatment may influence drug treatment
response in OCD patients.
Key words:
Obsessive compulsive disorder · Clinical predictors · Drug
response · Treatment duration.
P058
The development of psychosis in adolescence: associations
with depression, anxiety and drug use
C. J. Mackie; N.C. Castellanos; & P. J. Conrod. Institute of
Psychiatry, King’s College London, UK.
Background:
There is limited information about the evolution and
development of early onset psychosis symptoms across
adolescence. This study examined the trajectories of
psychosis in a sample of adolescents at elevated risk for
substance misuse and assessed whether development of
psychosis was associated with increases in depressive,
anxiety and drug use.
Methods:
319 adolescents (Mean age 14) who showed personality
risk factors for substance misuse comprised the current
sample. Developmental trajectories were defined using
questions on psychotic-like experiences adapted from
the Diagnostic Interview Schedule (Costello et al., 1982)
which are shown to be predictive of future schizophrenia
(Poulton et al. 2000) at four 6 month intervals (T1, T2,
T3 and T4). Main outcomes measures included nicotine
use, cannabis and cocaine use, quantity and frequency of
alcohol use, alcohol problems (Rutgers Alcohol Problems
Index, White & Labouvie, 1989), and depression
and anxiety symptoms (Brief Symptom Inventory;
Derogatis, 1993).
Results:
Three developmental subgroups of psychosis symptoms
were indentified through general growth mixture
modelling: 1) Early Onset/Persistence 2) Late Onset/
Increasing 3) Low. At all four time points, adolescents
with Early Onset/Persistence psychosis reported higher
scores in depression and anxiety (p < .0005) and at T3
100
and T4 higher rates of alcohol use (p < .04). At T3 and
T4, adolescents with a Late Onset/Increasing psychosis
reported higher rates of smoking, cannabis and cocaine
use (ps < .04) and higher number of alcohol use problems
(p < .02).
P059
Paranoid thinking, schizotypal personality traits and
cannabis use in relation to emotional decision-making
Stephanie Lynch, John JD Turner, Kirstie Soar
and Lynne Dawkins
Recreational Drugs Research Team, School of Psychology,
University of East London, Romford Road, London
E15 4LZ.
Background & Aims:
Recent work exploring the link between THC and psychosis
has begun to look into sub-psychotic behavioural features
and functions which may be affected by cannabis use.
For example, our previous work has shown a possible
effect of cannabis on schizotypy and associative learning
(Lynch and Turner, 2006). In the current pilot study, we
extended this examination of psychosis-linked features in
cannabis users: looking at paranoia, as a common trait
in psychotic experiences and as a widely reported sideeffect of cannabis use, schizotypy and performance on
the Iowa Gambling Task (IGT); an emotionally nuanced
measure of decision-making abilities.
Method:
A culturally and ethnically diverse sample of 55
undergraduate psychology students (11 males, 44
females; mean age 27), completed the Paranoid
Thoughts Scale (PTS; Green et al, 2008), Schizotypal
Personality Questionnaire SPQ; Raine 1991), a drug use
proforma and were then assessed on the IGT (Bechara et
al, 1994).
Results & Discussion:
As shown in previous studies, scores on the PTS (SR and
IP scores) and the SPQ (total, IP, CP, DT) were all positively
associated with each other (all p<0.05). There was a weak
but non-significant negative correlation between SPQ total
score and IGT performance (p= 0.09); suggesting that
those who displayed more psychotic-like personality traits
also took more risks during the decision-making task.
A weak trend was also found between the last time people
reported smoking cannabis and higher scores on the SR
subscale of the PTS (p=0.07); which links to previous
research showing that acute effects of cannabis can help
produce or exacerbate paranoid experiences. Performance
on the IGT was not clearly associated with cannabis use,
with a multiple regression analysis revealing that the only
significant predictor of scores on this task was the last
time participants had smoked tobacco (p =0.02); the
best scores being for those who had smoked on the day
of testing, as opposed to non-smokers or those who had
Collegium Internationale Neuro-Psychopharmacologicum
not smoked for 24 hours or more prior to testing. This
effect supports previous findings of cognitive facilitative
effects of nicotine; which may also have masked negative
effects of other drug use, including cannabis.
The IP subscale of the PTS was the only predictive trait
measure for decision-making with high scorers taking
fewer risks during the IGT (p =0.04); which indicates
that there was some type of affective contribution in
responding to this task; in particular higher levels of
anxiety, stress and/or some underlying paranoia led to
them being more responsive to threat (i.e. higher risk/less
reward) during the gambling task.
P061
The effects of antidepressants on BDNF productions
in PBMC culture of healthy subjects
Bun-Hee Lee, Yong-Ku Kim
Department of Psychiatry, College of Medicine,
Korea University, Seoul, Korea
Purpose:
We explored the effects of antidepressant agents on
Brain-derived neurotrophic factor (BDNF) productions in
peripheral blood mononuclear cells of healthy subjects.
Method: BDNF production was examined in culture
supernatants of unstimulated and LPS+PHA-stimulated
whole blood. Various drugs and various drug levels
(amitryptiline HCl: 10ng/ml, 100ng/ml, 1ug/ml, paroxetine
HCl: 5ng/ml, 50ng/ml, 500ng/ml, mirtazapine HCl:
5ng/ml, 50ng/ml, 500ng/ml, venlafaxine HCl: 15ng/
ml, 150ng/ml, 1.5ug/ml) were administered into culture
grounds, and then the unstimulated and stimulated whole
blood was cultured for 48 hours at 37 in a humidified
atmosphere containing 5% CO2.
Results:
The BDNF productions were not significantly altered in
unstimulated cultures with amitryptiline HCl, paroxetine
HCl, mirtazapine HCl, and venlafaxine HCl. There were
no significant changes of stimulated BDNF productions by
paroxetine HCl, mirtazapine HCl, and venlafaxine HCl.
However, stimulated BDNF productions were significantly
increased in supernatants with amitryptiline HCl (p=0.003).
There were no significant differences in unstimulated/
stimulated BDNF productions among each drug level of
amitryptiline HCl, paroxetine HCl, mirtazapine HCl, and
venlafaxine HCl.
Conclusions:
Our findings suggest that amitryptiline HCl might stimulate
the BDNF productions of peripheral blood cells. However,
paroxetine HCl, mirtazapine HCl, and venlafaxine HCl did
not alter BDNF production of blood cells.
P062
Differential effects of cannabis on the subjective
cognitive vulnerability in schizophrenic patients and
healthy controls
Ada Stadelmeier, Johannes Rentzsch, Zsofia Szirmak,
Daniela Knuth, Nicole Mauche, Sophia Wagner, Maria C.
Jockers-Scheruebl
Department of Psychiatry, Charité-University Medicine
Berlin, Germany
Introduction:
Cognitive impairments are a key feature of schizophrenia
and may be the most important determinant of disease
outcome. There is also some evidence for deficits in
cognitive functions in chronic cannabis users. However,
the influence of cannabis misuse on cognitive functioning
in patients with schizophrenia is not well understood. In
a former study we found better cognitive functioning in
abstinent schizophrenic patients with previous regular
cannabis misuse (Jockers-Scherübl et al., 2007).
Aim of study:
The aim of our on-going study project is to verify und
extend these results with particular respect to subjective
cognitive vulnerability.
Methods:
In an 2x2 study design so far 38 schizophrenic patients
(16 cannabis abusers and 22 nonabusers) and 54
healthy controls (27 cannabis abusers, 27 non- abusers)
were administered the “Subjective-Effects-of-Cognitive
Vulnerability-Scale” (DEV) whose items describe cognitive
every-day failures and correlate with the continous
performance test (CPT). In addition other objective
neuropsychological tests like the Trail-making-test
were carried out. All subjects had to be abstinent from
cannabis for at least 28 days; consumption of other illegal
drugs more than 5 times lifetime or misuse of alcohol
or any further axis I diagnosis according to ICD-10 led
to exclusion.
Results:
On the whole schizophrenic patients reached a higher
DEV mean score than healthy
controls. However, schizophrenic patients with regular
cannabis abuse prior to the first psychotic episode reached
a lower score meaning less every-day impairment. The
opposite occurred in the control group.
Conclusion:
Regular cannabis abuse seems to have a differential
effect on subjective cognitive functioning in schizophrenic
patients and healthy controls.
Key Words:
BDNF, culture, amitryptiline, paroxetine, mirtazapine,
venlafaxine
Major Psychoses and Substance Abuse
101
Poster Abstracts
P064
The Prevalence of Alcohol, Psychostimulant, and
Psychedelic Drug Abuse Among 15 to 35 years old
Tehranis in the year 2005
Mustafa Homdieh, “Sedighe Taraghigah”
Objective:
This cross-sectional study study has been performed
to give us a comprehensive view on the prevalence of
alcohol, psychostimulant, and psychedelic drug abuse
among teenagers and adults ranging 15 to 35 years old
residing in Tehran during the first 6 months of the year
2005.
Materials and Methods:
8175 individuals 15 to 35 years old from the 22
city councils participated in a survey from January to
June 2005.
Results: In answer to the question about psychostimulant
drug abuse, 89.5% answered “No”, 7% answered “Yes”
and 3.6% did not answer this question. The prevalence
of psychedelic drug abuse was 3.8%, psychostimulant
drug abuse was 7.2%, and alcohol abuse was 25.7%.
The mean age in each group of substance abusers was
similar to that of the whole sample, and the gender
distribution was significantly higher in5ng/ml, 50ng/ml,
500ng/ml, venlafaxine HCl: 15ng/ml, 150ng/ml, 1.5ug/
ml) were administered into culture grounds, and then the
unstimulated and stimulated whole blood was cultured
for 48 hours at 37 in a humidified atmosphere containing
5% CO2.
Results:
The BDNF productions were not significantly altered in
unstimulated cultures with amitryptiline HCl, paroxetine
HCl, mirtazapine HCl, and venlafaxine HCl. There were
no significant changes of stimulated BDNF productions by
paroxetine HCl, mirtazapine HCl, and venlafaxine HCl.
However, stimulated BDNF productions were significantly
increased in supernatants with amitryptiline HCl (p=0.003).
There were no significant differences in unstimulated/
stimulated BDNF productions among each drug level of
amitryptiline HCl, paroxetine HCl, mirtazapine HCl, and
venlafaxine HCl.
Conclusions:
Our findings suggest that amitryptiline HCl might stimulate
the BDNF productions of peripheral blood cells. However,
paroxetine HCl, mirtazapine HCl, and venlafaxine HCl did
not alter BDNF production of blood cells.
Key Words:
BDNF, culture, amitryptiline, paroxetine, mirtazapine,
venlafaxine
102
P064
The impact of substance misuse on brain structure in
subjects at high risk of developing schizophrenia
Welch KA, McIntosh AM, Job DE, Whalley HC, Moorhead
WJ, Owens DCG, Lawrie SM and Johnstone EC
Background:
Ventricular enlargement and reduced prefrontal volume
are among the most consistently replicated findings
in schizophrenia.1 Both are present in first-episode
subjects,2,3 and the latter may be detectable even
prior to the onset of clinical disorder.4,5 Substance
misuse is significantly more common in people with
schizophrenia6 and is associated with similar structural
brain abnormalities.7,8 However, no prospective study
has yet demonstrated an association between substance
misuse, brain abnormality and risk of schizophrenia.
Methods:
Substance misuse history, structural imaging data and
clinical information were collected on 147 subjects at
high risk of schizophrenia for genetic reasons. Prefrontal
and ventricular volumes were obtained by hand-tracing
these structures using established protocols. Misuse
of alcohol, cannabis or tobacco was then related to
regional brain volumes, with correction for potential
confounders. Multivariate regression was used to account
for correlations between these variables. Finally, we
established whether substance misuse was associated
with later risk of schizophrenia.
Results:
Increased ventricular volume was associated with both
alcohol and cannabis use in a dose-dependent manner.
Alcohol consumption was also associated with reduced
frontal lobe volume. Multiple regression analyses found
that both alcohol and cannabis were significant predictors
of these abnormalities when simultaneously entered into
the statistical model. Furthermore, alcohol and cannabis
misuse were also associated with an increased subsequent
risk of schizophrenia.
Discussion:
Here we provide prospective evidence that the use of
cannabis or alcohol in young people at high genetic risk
of schizophrenia is associated with brain abnormalities
and with later risk of psychosis. These findings suggest
that a close family history of schizophrenia may render
the brain particularly sensitive to the risk-modifying effects
of these substances.
References:
1. Lawrie SM, McIntosh AM, Hall J, Owens DG, Johnstone
EC. (2008) Brain structure and function changes
during the development of schizophrenia: the
evidence from studies of subjects at increased genetic
risk. Schizophrenuia Bulletin 34, 330-340.
Collegium Internationale Neuro-Psychopharmacologicum
2. Vita, A, De Peri, L, Silenzi, C, et al. (2006) Brain
morphology in first-episode schizophrenia: a meta analysis of quantitative magnetic resonance imaging
studies. Schizophrenia Research 82, 75 –88.
Benzodiazepine Withdrawal Symptom Questionnaire,
Visual Analogue Scale, Hamilton Depression Rating Scale
and Hamilton Anxiety Rating Scale. Serum Benzodiazepine,
Serotonin and Escitalopram were detected.
3. Hirayasu, Y, Tanaka, S, Shenton, ME, et al. (2001)
Prefrontal gray matter volume reduction in first episode
schizophrenia. Cerebral Cortex 11, 374 –381.
Results:
80% in the Escitalopram and 60% in the placebo groups
experienced successful benzodiazepine Withdrawal.
Analysis of Tyrer Benzodiazepine Withdrawal Symptom
Questionnaire score revealed a statistically significant
difference between the two studied groups indicating
that Escitalopram attesting to a decrease in the number
and intensity of withdrawal symptoms. These results
supported by significant improvement in Hamilton Anxiety
Rating scale, Hamilton Anxiety Rating scores and Visual
Analogue Scale.
4. Job DE, Whalley HC, McConnell S, Glabus MF, Johnstone
EC, Lawrie SM. (2003) Voxel based morphometry
of grey matter densities in subjects at high risk of
schizophrenia. Schizophrenia Research 64:1–13.
5. Diwadkar VA, Montrose DM, Dworakowski D, Sweeney
JA, Keshavan MS. (2006) Genetically predisposed
offspring with schizotypal features: an ultra
high-risk group for schizophrenia? Progress in
Neuropsychopharmacology and Biological Psychiatry
30, 230–238.
6. Dixon L. (1999) Dual diagnosis of substance abuse
in schizophrenia: prevalence and impact on outcomes.
Schizophrenia Research 35(suppl), S93-S100.
7. Krill JJ, Halliday GM, Svoboda MD, Cartwright H.
(1997) The cerebral cortex is damaged in chronic
alcoholics. Neuroscience 79, 983–998
8. Kril JJ & Halliday GM. (1999) Brain shrinkage in
alcoholics: a decade on and what have we learned?
Progress in Neurobiology 58, 381-7
P065
Evaluation of Escitalopram in the treatment of
Benzodiazepines Withdrawal Symptom
Ashraf M. Emara1, Mahmoud A. Omara2 and Mohamed
A. Abd El-Hay3
Forensic medicine & Clinical Toxicology1, Chemistry2 and
Neuropsychiatry3 departments, 1&3Faculty of Medicine
and 2Eduction (Kafer Elshekh), Tanta University, Egypt.
Background:
Benzodiazepines withdrawal can be associated with
symptoms that interfere with success of its gradual
withdrawal.
Aims:
Assessment of the possible efficacy of Escitalopram in
treating benzodiazepine dependence.
Methods:
Sixty male Egyptian benzodiazepine dependent subjects
were included in the present study. The study duration
was fourteen weeks, including six weeks experimental
treatment (gradual withdrawal phase), divided into four
phases. Subjects were given 20 mg of Escitalopram or
placebo twice daily for 10 weeks from the beginning of the
study. The withdrawal symptoms were assessed by Tyrer
Conclusions:
Escitalopram is helpful in management of Benzodiazepines
withdrawal.
P066
Risperidone long acting injection in bipolar disorder and
polysubstance use: a case report
S. Trandafir - Alexandru Obregia Hospital, Unit VII,
Bucharest - Romania
Comorbidity between substance abuse disorders and
mental illness, is notably prevalent in general population
with a prevalence up to a 86%. This association is known
as dual diagnosis. DD. Many bipolar I patients develop
comorbid substance use , often a poly drug use , with the
worst outcome .
I present a case of dual diagnosed patient , resistant
and non compliant to treatment , who showed prolonged
mood stabilization and reduction in use and craving for
alcohol , cannabis with risperidone long acting injection.
P.T. a 26 year old , diagnosed with Bipolar First Degree
Disorder and Polisubstance Use since adolescence . The
patient comes from a disorganised family with a mother
that is a scientific researcher in mathematics in the USA
and the father is remarried and lives with his wife and
their 10 years old daughter. As a teenager, the patient
has lived in the USA with his mother for a while, he had a
job and went to school but he left because he had started
using marihuana and cannabis. His mother sent him
back to the country because of the severe measurements
taken towards the drug users in the USA. He had lived
with his biological father and his new wife for a while but
the boy couldn’t fit into the family.
In the year 2006, at the age of 26, the patient presented
behaviour disorders, expansive disposition, loquacity,
delirious ediation with a mystic character- mania
with psychotic features and disruptive behaviour:
symptomatology for which the patient was hospitalized.
Major Psychoses and Substance Abuse
103
Poster Abstracts
In 2007 P.T. showed several manic episodes that required
prolonged hospitalization. Inter-episodes phases were
characterized by mood liability work impairment and
daily substance use .Treatments prescribed : zyprexa 20
mg/day , valproic acide 1200 mg/day were quickly and
autonomously discontinued after demision for sedation ,
cognitive impairment , non-compliance and begun also
cannabis use, and alcohol .
September 2007 the patient began the treatment on
Risperidone 6mg per day, valproic acide 1200 mg/
day for 3 weeks; After continue treatment only with
Rispolept Long Acting 50 mg every second week. For
the first time, P.T. showed compliance to pharmacological
and psychotherapical - family therapy treatment coming
to psychiatric unit as required by his physician. Mood
symptoms improved up to a complete stabilization,
without relapses.P.T . stopped cannabis assumption ,
reduced alcohol use till a complete abstinence without
craving.
Response for cannabis was slower, proved by urine drug
screen performed randomly .He had been going to a
psychotherapy group programme for 8 weeks.
At this time ,T.P. is still euthimic , adherent and content
with treatment .He doesn’t use alcohol , and cannabis .
Conclusions:
This case –report highlights risperidon long acting ‘s
effectiveness in mood stabilization , along with tolerability
, and a possible contribution to polisubstance craving
and use remission. More researches are needed to
establish the benefits of long acting risperidone in regard
to polysubstance use, many in particular to cannabis
and alcohol.
References:
1.Martin S.D., Libereto SE,Pratt DJ ,et all , Clinical
experience with the long-acting injectable formulation of
the atypical antipsychotic, rieperidone , Curr .Med .Ress
Opin 2003;19;298-305
2. Kane JM, Eerdeken M , KeithSJ, et all , efficacy and
safty of novel long acting risperidone microspheres
formulation , Am Jpsychyatry ,2003;61125-32
P067
Illicit substance misuse does not have a detrimental effect
on executive function and working memory in first episode
psychosis
Kim. Donoghue1, Rodolfo. Mazzoncini2, Jozella. Hart2,
Jolanta. Zanelli2, Abraham. Reichenberg2, Craig. Morgan,
C2, Paul. Fearon2, Paola. Dazzan2, Robin. M. Murray2,
Peter. B. Jones3, Gillian. A. Doody1.
1
Division of Psychiatry, University of Nottingham,
Nottingham, U.K.
2
Institute of Psychiatry, Kings College London,
London, U.K.
3
Department of Psychiatry, University of Cambridge,
Cambridge, U.K.
104
Introduction:
There is evidence of a detrimental effect of illicit drug use on
cognitive function in healthy individuals. Due to cognitive
impairment being a feature of psychotic disorders such
as schizophrenia and bipolar disorder, there is concern
that a psychotic disorder plus the misuse of illicit drugs
may result in a more pronounced deficit in cognitive
function. The aim of this study is to investigate the effect of
illicit substance misuse on executive functioning and
working memory in individuals with a first-episode
psychotic disorder.
Method:
Neuropsychological tests that assessed executive
function and working memory were administered to
102 first-episode psychosis patient’s, recruited in the
city of Nottingham, as part of the AESOP study, a multicentre epidemiological study of first-episode psychosis.
A comorbid diagnosis of harmful use or dependence
of illicit substances using the International Classification
of Diseases (ICD-10) was assigned by consensus
diagnosis and recreational substance use that did not
meet ICD-10 criteria for harmful use or dependence was
established retrospectively. Participants with harmful use/
dependence of substances (n=15) and participants who
used substances recreationally (n=24) were compared
for their performance on tests of executive function and
working memory with those participants with no history of
substance use (n=55).
Results:
There were no differences in neuropsychological test
performance when comparing either of the two substance
use groups with non-drug users, with the exception of the
Trail making-B test, a test of executive function. When
controlling for age and gender differences, participants
with a diagnosis of harmful use or dependence performed
significantly better than non-drug users. However, there
was no difference in performance between participants
with recreational drug use only and non-drug users.
Conclusion:
Illicit substance misuse in patients with a first episode of
psychosis is not associated with a greater impairment in
executive function and working memory and may even be
associated with better executive function.
P068
[18F]-Labelled benzamides as probes for microPET
studies of amphetamine-evoked dopamine release in
rodent brain
Paul Cumming, Axel Rominger, Erik Mille, Erika Wagner,
Björn Wängler, Franz-Josef Gildehaus, Klaus Tatsch, Peter
Bartenstein
Department of Nuclear Medicine, Ludwig-Maximilans
University, Munich, Germany
Collegium Internationale Neuro-Psychopharmacologicum
Aim:
The competitive binding of benzamide radioligands at
dopamine D2-receptors has been employed to great
effect for molecular imaging studies of dopamine release
in living human brain. However, PET ligands labelled
with C-11 are generally only available at research sites
with cyclotron-radiochemistry facilities, whereas SPECT
methods suffer from limited spatial resolution. Therefore,
we endeavoured to characterize the vulnerability of the
high affinity benzamide ligand [18F]fallypride (FP), and its
lower affinity congener [18F]desmethoxy-[18F]fallypride
(DMFP) to endogenous competition in mouse brain. We
also studied the kinetics of the vulnerability of DMFP
binding in rat brain to amphetamine-evoked dopamine
release.
Methods:
Groups of awake mice were pretreated with saline,
amphetamine (10 mg/kg) or reserpine (5 mg/kg), followed
by i.v. tracer injections. Mice were killed at 2.5 to 90 min
(DMFP) or 2.5 to 210 min (FP). Brains were dissected, and
regional radioactivity concentration measured by gamma
counting. Other groups of mice were anesthetized for FP
or DMFP microPET recordings, in which four mice were
scanned simultaneously. Constructed or measured timeradioactivity curves were used to calculate the binding
potentials (BP) using cerebellum as reference region. In
rat DMFP studies, dynamic emission recordings were
obtained after bolus injection, or at steady-state binding,
during continuous DMFP infusion. Binding potential (BP)
maps were calculated by conventional methods in saline
and amphetamine-treated rats, and transformed into a
standard coordinate system for mouse or rat brain.
Results:
As calculated ex vivo, the BP in striatum was 2.7 for DMFP
was 2.7, versus 19 for FP. The corresponding microPET BPs
were 50% lower. DMPF proved to be highly vulnerable to
amphetamine challenge, declining by as much as 50% in
the microPET studies, as increased by 20% after reserpine
treatment. FP was likewise vulnerable to competition
from endogenous dopamine. Similarly, the bolus and
infusion microPET methods both indicated amphetamine
vulnerability of DMFP binding in rat striatum.
Conclusions:
Both FP and DMFP were highly vulnerable to altered
competition from endogenous dopamine in rodent
striatum. However, the microPET BPs were underestimated,
due to spill-over from striatum, and also spill-in of bone
signal to cerebellum, which was the major factor resulting
in biased microPET estimates, relative to gold standard
ex vivo results. Bolus and steady-state DMFP infusion
methods were both suitable for revealing psychostimulant
action in rat microPET studies. Thus, the [18F]labelled benzamides should make the amphetamine
challenge paradigm accessible to PET centres lacking a
cyclotron unit.
P069
The effects of Δ9-tetrahydrocannabinol on depression
and anxiety
Morgan, CJA, Freeman, T., Schäfer, G., Curran, H.V.
Clinical Psychopharmacology Unit, University College
London, Gower St, LONDON, WC1E 6BT
Background and Aims:
The link between cannabis use and psychosis has been
subject to a good deal of media and scientific attention,
whilst the association between cannabis use and mood
disorders has been less well researched. Their has been
some suggestion that the main constituent of cannabis,
Δ9-tetrahydrocannabinol (THC) may acutely have antidepressant properties (Serra & Fratta, 2007) and that the
second most abundant cannabinoid cannabidiol (CBD)
is anxiolytic in humans (Zuardi et al., 2006). This study
aimed to assess the link between cannabis use, mood and
mood disorders link using THC acid levels measured from
urine samples and CBD and THC levels in naturalistically
smoked cannabis.
Method:
106 cannabis users and 33 non-cannabis using controls
were tested on 2 separate occasions –while the cannabis
users were intoxicated with their own naturalistically
smoked cannabis and again when drug free – for state
anxiety, euphoria and anhedonia, depression, trait
anxiety, dependence and vulnerability factors such as
childhood trauma.
Results:
Level of THC acid in urine was found to be a significant
predictor of depression in vulnerable individuals.
Cannabis dependence also strongly predicted depression.
State anxiety, anhedonia and euphoria were all higher
in cannabis users when intoxicated. These symptoms
decreased when drug free, though anhedonia remained
significantly higher in daily cannabis users on the drug
free day compared to recreational users and controls.
Acutely THC, CBD or the ratio of the two cannabinoids
in smoked cannabis were not associated with euphoria,
anxiety or anhedonia.
Conclusions:
Greater THC levels in urine of cannabis users and
dependence on the drug were found to be associated
with increased incidence of depression. This elevation of
depressive symptoms may be related to lifestyle factors
associated with regular cannabis use or may possibly
be related to disruptions of the endocannabinoid system
from prolonged, heavy use of the drug.
Major Psychoses and Substance Abuse
105
Travel Information
Travel by Car
As Edinburgh is located at the heart of the Scottish Motorway network, it is relatively easy to travel by car. To help plan your
journey, the following websites may be useful:
The AA Route Planner
www.theaa.com
MultiMap
www.multimap.com
Travel by Train
Edinburgh is extremely accessible by train. The Great North Eastern Railway (GNER) is the fastest intercity railway in the
UK, with a journey time of approximately 4 hours between Edinburgh (Waverley) and London (King’s Cross).
Edinburgh train station has great rail links to other major cities; York, Newcastle, Inverness and Aberdeen are all about 2
hours travel by train, and Glasgow is just 50 minutes on the First Scotrail shuttle service which leaves Waverley train station
every 15 minutes. The following companies can provide more information:
National Rail Enquiries
08457 48 59 50
Virgin Trains
08457 22 23 33
Travel by Bus
Travelling by bus to Edinburgh is a great option especially for those on a budget. There are regular coach services to
Edinburgh from all major UK cities. The following companies can provide more information:
National Express
08705 80 80 80
Scottish Citylink
08705 50 50 50
Travel Line Scotland
08706 08 26 08
Travel from Airport
By bus- Public bus services stop outside the UK Arrivals doors on the terminal forecourt.
Airlink 100 to city centre
There is an express bus service to Edinburgh city centre. The frequency of the service is from every 10 minutes at peak
times through the day, to every 30 minutes at night. The journey takes approximately 25 minutes and terminates at
Waverly Bridge, near to the main railway station (Waverly) and bus station and is just off the city’s main street, Princes
Street.
Travel by taxi
Taxis (cabs) are available from a designated rank beside the coach park outside the UK arrivals hall. A typical journey
time to the city centre takes around 25 minutes and fares vary according to the distance travelled. Many of the taxis are
wheelchair accessible.
More information can be found on the Edinburgh International Airport website www.edinburghairport.com
106
Collegium Internationale Neuro-Psychopharmacologicum
List of delegates
Ercan Abay, Janssen Cilag Turkey, Turkey
Mohamed Ali Abdel Azez Ghazy, Almanea, Saudi Arabia
Aytul Gursu Abdulhussein Hariri, Erenkoy Ruh Sagligi Ve Hastaliklari Egitim Ve
Arastirma, Turkey
Klaus Abel, Lundbeck Australia, Australia
Maria Jose Abella Arosa, Spain
Abdulwahd Abojaziah, Al Bostan, Saudi Arabia
Mohamed Abou Zaid, Psychiatry Hospital, Kuwait
Abiodun O. Adewuya, Lagos State University College of Medicine, Nigeria
Hakan Adigüzel, Santa Farma, Turkey
Claudio Ague, SEPT NHS UK, UK
Beny Ahuva, Eli Lilly Israel, Israel
Nikolaos Aivalis, Lundbeck Hellas, Greece
Zelkif Akgul, Sanofi Aventis Turkey, Turkey
Zeynep Bodur Akgul, Bornova Acil Yardim Ve Travmatoloji Hastanesi, Turkey
Ali Akkök, Pasabahce Devlet Hastanesi, Turkey
Selami Aksoy, Karsiyaka Devlet Hastanesi - Izmir, Turkey
Umut Mert Aksoy, Santa Farma, Turkey
Hatice Aksu, Sanofi Aventis Turkey, Turkey
Muhammet Gokhan Aksu, Sanofi Aventis Turkey, Turkey
Majid Al Abdullah, Hamad Medical Complex, Qatar
Hassan Al Amry, Assir Central Hospital, Saudi Arabia
Osama Al Ibrahim, Al Amal Hospital, Saudi Arabia
Rashad Al Senosy, Gizan Psychaitry Hospital, Saudi Arabia
Krasimira Aldinova, Bulgaria
Abdelsamad Algeshi, Aramco, Saudi Arabia
Javed Ehtesham Ali, Cape Breton Regional Hospital, Canada
Khalaf Al-Jomaa, Al-Amal Mental Health Complex, Saudi Arabia
Tunc Alkin, Janssen Cilag Turkey, Turkey
Koksal Alptekin, Sanofi Aventis Turkey, Turkey
Hassan Al-Rawy, Al-Sherief, Saudi Arabia
Saleh Al-Shebil, King Fahd National Guard Hospital, Saudi Arabia
Murat Altýn, Tokat Devlet Hastanesi, Turkey
Nawaf Al-Zeidi, Al-Amal Mental Health Complex, Saudi Arabia
Þenol Anaç, Ozel Imperial Hastanesi, Turkey
Manjunatha Anantharamu, NHS Forth Valley, United Kingdom
Spyridon Apostolou, Lundbeck Hellas, Greece
Gokhan Arabul, Balikesir Devlet Hastanesi, Turkey
Mikkel Arendt, Department for Psychiatric Research, Aalborg Psychiatric Hos,
Denmark
Zhera Arikan, Gazi Ün. Tip Fakültesi, Turkey
Konstantinos Asimakopoulos, Lundbeck Hellas, Greece
Atilla Aslan, Schering Plough, Turkey
Suat Sabri Aslan, Sanofi Aventis Turkey, Turkey
Abdel Rahman Assal, Al Hada Military Hospital, Saudi Arabia
Monica Astals Vizcaino, Laboratories Janssen Cilag, Spain
Figen Atalay, Haydarpasa Numune Hastanesi - Istanbul, Turkey
Genul Aydogan, Janssen Cilag Turkey, Turkey
Ýlke Aydogmuþ, Aksehir Devlet Hastanesi, Turkey
Ozlem Devrim Aykanat, Afyonn Kocatepe Devlet Hastanesi, Turkey
Larry Nanjul Ayuba, Northgate Hospital, UK
Alexandra Bagney, Spain
Piet Bakx, Forensic Psychiatric Hospital Veldzicht, The Netherlands
Ceyhan Balci Sengül, Santa Farma, Turkey
Ilias Balias, Lundbeck Hellas, Greece
Yang Weon Bang, Keyo Hospital, South Korea
Montserrat Bañuelos Piñol, Sant Joan de Deu/Servei Sawt Mental, Spain
Juan Carlos Barbolla Sancho, H.De Neuropsiquiatria Pontevedra/Centro Sawd
Lerez, Spain
Ana Maria Cerqueira Barbosa, Janssen Cilag Portugal, Portugal
Maria Basta, Lundbeck Hellas, Greece
Charalampos Bastas, Lundbeck Hellas, Greece
Khalid Bazaid, Aramco Hospital, Saudi Arabia
Mª Teresa Bel, Fundacio Hospital de Mollet, SPAIN
Joseph Belanoff, Corcept Therapeutics, United States
Lütfullah Beþiroglu, Yuzuncu Yil Universitesi Tip Fakultesi, Turkey
Sunar Birsoz, Sanofi Aventis Turkey, Turkey
Jose Maria Blanco Lobeiras, Hospital Provincial Potenepra, Spain
Boris Bodnar, University Hospital, Slovak republic
Madlena Borisova, MBAL “Ivau Rilski” Psychiatric Practice, Bulgaria
Aslý Bostancý, Bahcelievler Semt Poliklinigi, Turkey
Nesrin Karamustafalioglu Bozkan, Bakirkoy Ord. Prof. Dr. Mazhar Osman Ruh
Sagligi ve, Turkey
Maja Bundalo Boi, Slovenia
Victoria Burtea, Brasov Hospital, Romania
Francisco Lima Buta, Janssen Cilag Portugal, Portugal
Seher Çakmak Yuvanc, Santa Farma, Turkey
Sibel Çakýr, I.U Istanbul Tip Fakultesi, Turkey
Recep Calik, Ankara Egitim ve Arastirma Hastanesi, Turkey
Celal Çalikusu, Santa Farma, Turkey
Jose Canive, Raymond G. Murphy VA Med Center, USA
Tarik Canpolat, Janssen Cilag Turkey, Turkey
Qiuyun Cao, Nanjing Gulou Hospital, China
Luciano José Cardoso Moura, Janssen Cilag Portugal, Portugal
Robin Carhart-Harris, University of Bristol, UK
Jonathan Carne, Consultant Forensic Psychiatrist, Australia
Claudio Castillo, Hospital del mar, Spain
Ahmet Çelikkol, Santa Farma, Turkey
Esen Cengizler, Sanofi Aventis Turkey, Turkey
Mehmet Emin Ceylan, Barkirkoy Ruh ve Sinir Hastaliklari Hastanesi - Istanbul,
Turkey
Kalaitzi Chrysanthi, Greece
Zhongjun Chu, GlaxoSmithKline China, China
Rahmi Cihan, Sanofi Aventis Turkey, Turkey
Aylin Citken, Sanofi Aventis Turkey, Turkey
Massimo Clerici, University of Milano Bicocca, Italy
Lucinda Cockayne, Cameron Hospital, UK
Susanna Maria Colciago, Universita di Milano, Italy
Jan Copeland, University of NSW, Australia
Blanca Coromina Coll, Janssen Cilag, Spain
Maria Alexandra Corte Real, Janssen Cilag Portugal, Portugal
Behcet Cosar, Sanofi Aventis Turkey, Turkey
Ozlem Coskun, Janssen Cilag Turkey, Turkey
Ian Creese, Rutgers, USA
Paul Cumming, Klinikum Grosshadern, Germany
Wanglei Dai, The Second Affiliated Hospital of Wenzhou Medical College,
China
Magda Dantas, Janssen Cilag Portugal, Portugal
Hussain Dardas, K.F.H.U, Saudi Arabia
Natalia del Campo, University of Cambridge, UK
Selim Demirci, Sanofi Aventis Turkey, Turkey
Arsime Demjaha, Institute of Psychiatry, UK
Abdulnabi Derbas, Salmaniya Medical Complex, Bahrain
Lorena Di Carlo, Lundbeck Australia, Australia
Maria Dimitrakoudi, Hospital Castalia, Greece
Christina Dimitriou, General Hospital Larisa, Greece
Georgios Dimopoulos, Lundbeck Hellas, Greece
Kim Donoghue, University of Nottingham, England
Vitor Manuel Rodrigues dos Santos, Janssen Cilag Portugal, Portugal
Lora Drianovska-Tzoueva, Bulgaria
David Duncan, Saskatchewan Hospital, Canada
Todd Durell, Eli Lilly and Company, USA
Emmanuel Edeki, Lagos State University, Nigeria
Lumisa Edward, Youth Crime Watch uganda, Uganda
Christoph Eisenegger, Institut for Empirical Research in Economics, Switzerland
Adel El Zaid, Psychiatry Hospital, Kuwait
Yasein Elgadal, ARAMCO, Saudi Arabia
Sukru Kaya Elverici, Sanofi Aventis Turkey, Turkey
Ivar Elvik Jørgensen, Stavanger University Hospital, Norway
Brett Emmerson, Royal Brisbane & Women’s Hospital, Australia
Louise Emsell, NUI Galway, Ireland
Cengiz Epikmen, Sanofi Aventis Turkey, Turkey
Orkun Eray, GSK Turkey, Turkey
Duygu Erdagdu, Janssen Cilag Turkey, Turkey
Gonul Erdal, Ankara Yuksek Ihtisas Egitim ve Arastirma Hastanesi, Turkey
Ibrahim Eren, Janssen Cilag Turkey, Turkey
Kenan Eren, Santa Farma, Turkey
Gamze Ergil Altýn, Tokat Recep Yazicioglu Devlet Hast., Turkey
Sahap Erkoc, Janssen Cilag Turkey, Turkey
Mehmet Eryilmaz, Santa Farma, Turkey
Ilhan Eslek, Sanofi Aventis Turkey, Turkey
Ulrich Ettinger, Institute of Psychiatry, UK
Bilge Evren, Santa Farma, Turkey
Cüneyt Evren, Santa Farma, Turkey
Orietta Cinzia Facincani, University of Milan, Italy
Anna Falces Bascompte, CSM Mollet, Spain
Major Psychoses and Substance Abuse
107
List of delegates
Gabor Faludi, Semmelweis University Kutvolgyi Clinic, Hungary
Hazem Farghaly, Al-Amal Mental Health Complex, Saudi Arabia
Lisa Fawcett, Royal Brisbane & Women’s Hospital, Australia
Sean Feeney, Kent & Medway NHS & Social Care Trust, England
Susana Margarida Fernanades Fonseca, Janssen Cilag Portugal, Portugal
Leonor Manuela Ferreria Carneiro, Janssen Cilag Portugal, Portugal
Matjaz Ficko, PLIVA Slovenia, SLOVENIA
Loretina Florescu, County Hospital Targoviste, ROMANIA
Androniki Fotiadou, General Hospital Ioannina, Greece
Dimos Fotopoulos, Greek Organisation Against Drugs - Okana, Greece
Dimos Fotopoulos, Greece
Tom Freeman, UCL, United Kingdom
Heather Fulton, Dalhousie University, Canada
Aikaterini Georgopoulou, Lundbeck Hellas, Greece
Alexandros Gerontas, Psychiatr General Hospital Athens, Greece
Dimitrios Geroukalis, Lundbeck Hellas, Greece
Vrasidas Giannakopoulos, Lundbeck Hellas, Greece
Dimitrios Gkalios, Lundbeck Hellas, Greece
Aziz Mehmet Gokbakan, Dr. Ekrem Tok Ruh ve Sinir Hastaliklari Hastanesi,
Turkey
Burcu Goksan, Istinye Devlet Hastanesi, Turkey
Ali Saffet Gonul, Ege Universitesi Tip Fakultesi Hastanesi, Turkey
Kimberley P Good, Dalhousie University, Department of Psychiatry, Canada
Peter Grimes, The Spinney Psychiatric Hospital, UK
Ping Gu, GlaxoSmithKline China, China
Xiuling Gu, Beijing Chao-Yang Hospital, China
Mustafa Kadri Gucer, Akdeniz Universitesi Hastanesi - Antalya, Turkey
Cassiano Antonio Guimarães Pacheco Santos, Janssen Cilag Portugal, Portugal
Ali Riza Gulbahar, Sanofi Aventis Turkey, Turkey
Tugba Guven, Sanofi Aventis Turkey, Turkey
Oren Hagay, Eli Lilly Israel, Israel
Mary Hamilton, Sheffield Health & Social Care NHS F.T, UK
Christer Härnryd, Construct Of Mind, Sweden
Jo Hart, Institute of Psychiatry, UK
Tonje Hegranes, Stavanger University Hospital, Norway
Cécile Henquet, Maastricht University, The Netherlands
Amelia Hill, North Sydney Central Coast Area Health, Australia
Debra Hoffmeyer, Clinical Innovations, Inc., USA
Jiri Horacek, ZENTIVA CZ, Slovakia
Sibylle Hornung-Knobel, Isar-Amper-Klinikum, Germany
Luchezar Hranov, University Hospital in Neurology & Psychiatry, Bulgaria
Tarek Ibrahim, Erfan and Bagedo Hospital, Saudi Arabia
Lygeri Iliopoulou, General Hospital of Ioannina, Greece
Inna Ioannidou, Lundbeck Hellas, Greece
Erdal Isik, Ankara Gazi Universitesi Tip Fakultesi, Turkey
Süreyya Isik, Santa Farma, Turkey
Hasmet Iþýklý, Kasimpasa Askeri Hastanesi, Turkey
Lorraine Johnstone, Directorate of Forensic Mental Health, UK
Kyung Hee Jung, Keyo Hospital, South Korea
Jiang Kaida, Shanghai Mental Health Center, China
Yousuf Kamal Mirza, IBN Sina, Oman
Selma Kandil, Janssen Cilag Turkey, Turkey
Sukriye Kaplan, Janssen Cilag Turkey, Turkey
Selami Karaaslan, Sanofi Aventis Turkey, Turkey
Pervin Karakas, Bartin Devlet Hastanesi, Turkey
Oguz Karamustafalioglu, Istanbul Sisli Etfal ve Arastirma Hastanesi, Turkey
Aysem Özlem Kaya, Schering Plough, Turkey
Cemal Kaya, S. Urfa Devlet Hastanesi, Turkey
Ahmet Nuri Kibaroglu, Haseki Egitim ve Arast. Hast., Turkey
Daniël Kleinloog, Centre for Human Drug Research, Netherlands
Aysegul Koc, Sanofi Aventis Turkey, Turkey
Wilfried Köhler, Buergerhospital Frankfurt, Germany
Monique Konings, GGzE, Centre of Acute Psychiatry, the Netherlands
Ramazan Konkan, Bakirkoy Ord. Porf. Dr Mazhar Osman Ruh Sagligi Ve, Turkey
Demet Korezlioglu, Santa Farma, Turkey
Michail Kosmidis, Lundbeck Hellas, Greece
Dimitrios Kountouras, Psychiatr General Hospital Athens, Greece
Konstantinos Kousidis, General Hospital Larisa, Greece
Feride Manisali Kulayeva, Urla Devlet Hastanesi, Turkey
Jelena Kunovac, Excell Research, USA
Celalettin Kutcan, Yavuz Selim Devlet Hastanesi, Turkey
Ibrahim Kutluer, Santa Farma, Turkey
Aylin Kýlýç, Santa Farma, Turkey
108
Marc Laruelle, GlaxoSmithKline R & D Ltd, UK
Arseniy Lavrov, i3 Research, UK
Kuang Li, 1st Affiliated Hospital Chongqing University of Medical Scie, China
Naizhong Li, Huashan Hospital of Fudan University, China
Shuying Li, The First Affiliated Hospital of Zhengzhou Hospital, China
Baohua Liang, Xuanwu Hospital of Capital Medical University, China
Jean-François Liégeois, University of Liège, Belgium
Lois Ligate, Trellis, Canada
Fang Lin, Fujian Province Coalmine Center Hospital, China
Liming Lin, GlaxoSmithKline China, China
Li Liu, The First Hospital of China Medical University, China
Charalampos Lixouriotis, General Hospital of, Greece
Leonora Long, Prince of Wales Medical Research Institute, Australia
Dan Lubman, University of Melbourne, Australia
Selda Lüleci, Esenyurt Devlet Hastanesi, Turkey
Stephanie Lynch, University of East London, UK
Xin Ma, Beijing An Ding Hospital, China
Bill MacEwan, University of British Columbia, Canada
Clare Mackie, Institute of Psychiatry, KCL, UK
Takuya Maemoto, Astellas Pharma Inc, Japan
Rozalina Makelova, ODPZS - Prof. Temkov, Bulgaria
Maria Makowska, Prince Charles Hospital, Australia
Evgenia Makri, Lundbeck Hellas, Greece
Emma Malcolm, Newcastle University, UK
Chenhui Mao, GlaxoSmithKline China, China
Carla R. Marchira, Novartis Indonesia, Indonesia
Dragos Marinescu, University Hospital Craiova, Romania
Vasileios Marinos, Lundbeck Hellas, Greece
Hugh Marston, Schering Plough Research Institute, UK
Ricardo Martinez, Spain
Elefterios Mastoridis, General Hospital Kilkis, Greece
Jaqueline Mayoral Van-Son, Janssen Cilag, Spain
Dieter Meier, NeuroSearch, Denmark
Romulo Meira, Santa Izabel Hospital, Brasil
Maria Manuela Santos Mendes Moura, Janssen Cilag Portugal, Portugal
Handan Yilmaz Meteris, Santa Farma, Turkey
Ozmen Metin, Janssen Cilag Turkey, Turkey
Ioana Miclutia, Emergency County Hospital Cluj Napoca, Romania
Roumen Milev, Queen’s University, Canada
Arian Mobascher, Heinrich-Heine University Dusseldorf, Germany
Andy Montgomery, Peninsula Medical School, UK
Teresa Moreno, University Hospital Marques de Valdecilla, Spain
Celia Morgan, University College London, UK
Polyxeni Mourtzouchou, Lundbeck Hellas, Greece
Georgios Mousas, Attikon University General Hospital, Greece
Georgios Moussas, Attikon Hospital, Greece
Michael Nitsche, Georg-August-University, Germany
Zeynep Ocal, GSK Turkey, Turkey
Adegboyega Ogunwale, Neuropsychiatric Hospital, ARO, Nigeria
Melise Ogut, Sincan Dr. Nafiz Korez Devlet Hastanesi, Turkey
Tuncer Ihsan Okay, Sanofi Aventis Turkey, Turkey
Natália Maria Oliveira Fernandes, Janssen Cilag Portugal, Portugal
Osman Aga Onal, Goztepe Egitim Arastirma Hastanesi - Istanbul, Turkey
Ziya Onder, Janssen Cilag Turkey, Turkey
Rabia Fatma Ay Onen, Eskisehir Ozel Umit Tip Merkezi, Turkey
Sinan Orhan, Bursa Inegol Devlet Hastanesi, Turkey
Zahide Orhon, Santa Farma, Turkey
Hande T. Osmanagaoglu, GSK Turkey, Turkey
Cuneyt Muhsin Oy, Sanofi Aventis Turkey, Turkey
Suha Ozaskinli, Sanofi Aventis Turkey, Turkey
Armagan Ozdemir, Janssen Cilag Turkey, Turkey
Hakan Ozdemir, Santa Farma, Turkey
Ali Riza Ozen, Karsiyaka Devlet Hastanesi, Turkey
Ali Özkan, Topcular Semt Poliklinigi, Turkey
Evrim Ozkorumak, Rize Egitim Ve Arastirma Hatanesi, Turkey
Semih Ozlap, Janssen Cilag Turkey, Turkey
Levent Oztekin, Sanofi Aventis Turkey, Turkey
Eylem Özten, Giresun Ilhan Ozdemir State Hospital, Turkey
Havva Ozunalan Ozturk, Istanbul Bakirkoy Dr.Sadi Konuk Egitim ve Arastirma
Hastanes, Turkey
Ozgur Ozturk, Sanofi Aventis Turkey, Turkey
Xiaoping Pan, The First People Hospital of Guangzhou, China
Apostolos Papapostolou, Lundbeck Hellas, Greece
Collegium Internationale Neuro-Psychopharmacologicum
Andreas Papatheodorou, Private Doctor, Greece
Santiago Parada Nieto, Complejo Hospitalario Pontevedra, SPAIN
Hitendra Parmar, Pfizer Ltd, UK
Ioanna Pediaditaki, Lundbeck Hellas, Greece
Cherry Pedler, Lambeth (CSN), UK
Diana Peeva-Teneva, DPB - Kardjali, Bulgaria
Yao Peifen, Shanghai Mental Health Center, China
Joaquim Jorge Peixoto Gonçalves, Janssen Cilag Portugal, Portugal
Tahsin Pektoylan, Cerkirge Devlet Hastanesi, Turkey
Emilia Pereira, Janssen Cilag Portugal, Portugal
Damianos Petrou, Lundbeck Hellas, Greece
Rozalina Petrova, MBAL Iban Seleminski, Bulgaria
Mihail Pirlog, University Hospital Craiova, Romania
Paavo Pokk, Tartu University, Estonia
Guillermo Ponce, Hospital Universitario 12 de Octubre, Spain
Stephen Jay Proud, Nióla Private Psychiatric Hospital, Australia
Claudia Radut, Fabrio Turism, Romania
Francisco Javier Ramon, Spain
Adolfo Revuelta, Spain
Hedva Reznik-Cohen, Eli Lilly Israel, Israel
Georgios Rigas, Lundbeck Hellas, Greece
Velez Rita, Janssen Cilag Portugal, Portugal
Zeferino Venade Robeiro, Janssen Cilag Portugal, Portugal
Roberto Rodriguez-Jimenez, Hospital Universitario 12 de Octubre, Spain
Juan Carlos Romero, Spain
Fernanda Maria Leal S. Rosa, Janssen Cilag Portugal, Portugal
Basri Seçkin Ruscuk, Santa Farma, Turkey
Samantha Rushforth, University of Newcastle, UK
Maja Rus-Makovec, University Psychiatric Hospital Ljubljana, Slovenia
Hesham Sabry, Janssen Cilag, Saudi Arabia
Turgay Saglam, Yedikule Psikiyatri Dal Merkezi, Turkey
Saddichha Sahoo, Emergency Management and Research Institute (EMRI), India
Luzia Maria Avelino Sales Delgado, Janssen Cilag Portugal, Portugal
Armagan Samanci, Santa Farma, Turkey
Mehtap Saribas Topuz, Sanofi Aventis Turkey, Turkey
Ali Murat Sarsam, Santa Farma, Turkey
Peter Sayer, Ocean Media Group Ltd, UK
Melike Saygýlý, Seyhan Arastirma Hospital, Turkey
Loris Sayyan, DDPDS, Bulgaria
Thomas Schnell, University of Cologne, Germany
Chris Schubart, Rudolf Magnus Intitute of Neuroscience, Netherlands
Linda Scoriels, University of Cambridge, UK
Murat Seker, Icel Ozel Ozde Tip Merkezi, Turkey
Cem Sengül, Santa Farma, Turkey
Adel Seraj, Soliman Fakeeh Hospital, Saudi Arabia
Firdevs Seyfe Sen, Turgutlu Devlet Hastanesi B Blok, Turkey
Ülkü Sezgin, Santa Farma, Turkey
Hadar Shalev, Eli Lilly Israel, Israel
Shenxun Shi, Huashan Hospital of Fudan University, China
Tianmei Si, 6th Affiliated Hospital of Peking University, China
Sanjay Siddhartha, Canada
José Ferreira Silva, Janssen Cilag Portugal, Portugal
Eirini Simintzi, Lundbeck Hellas, Greece
Ioanna Skandalaki, Lundbeck Hellas, Greece
Karel Slais, Faculty of Medicine, Masaryk University, Czech Republic
Cayne Smith, The Spinney Psychiatric Hospital, UK
Maria Celeste Sousa Silveira, Janssen Cilag Portugal, Portugal
Renan Souza, Centre for Addiction and Mental Health, Canada
Ada Stadelmeier, Charité-University Medicine Berlin, Germany
Mariana Stefkova, Zentiva Group CZ, Slovakia
Theofilos Stergiou, Lundbeck Hellas, Greece
Sherry Stewart, Dalhousie University, Canada
Maya Stoimenova-Popova, University Hospital of Neurology and Psychiatry,
Bulgaria
Stoyan Storyanov, Ozone Laboratories Bulgaria, Bulgaria
Deyau Stoyanov, ODPZS Prof. Temkov, Bulgaria
Lucija Strmsnik, Torrex Chiesi Slovenija d.o.o, Slovenia
David Summers, Queen’s University, Canada
Øyvind Svendsen, Stavanger University Hospital, Norway
Maria Tajes Alonso, Provincial Conxo, Spain
Arzu Tamgac, Istanbul Taksim Arastirma Hastanesi - Istanbul, Turkey
Wenzhong Tang, Shanghai Mental Health Center, China
Maria Pilar Tarrio Otero, Casa del Mar Mollabas, spain
Ivan Tianev, MBAL- Targovishte, Bulgaria
Ahmet Tiryaki, Janssen Cilag Turkey, Turkey
Alexandru Tiugan, Fabrio Turism, Romania
Kaan Toksöz, Santa Farma, Turkey
Judit Tolna, Semmelweis University Department of Psychiatric, Hungary
Demet Topcuoglu, Lundbeck - Turkey, Turkey
Edit Toth Tegene, Orion Pharma, Hungary
Charalampos Touloumis, Psychiatr General Hospital Athens, Greece
Maria -Silvia Trandafir, Prof. Dr. ALEXANDRU OBREGIA Hospital, Romania
Eirini Tserpeli, Lundbeck Hellas, Greece
Faruk Tufekci, Turkey
Verda Tüzer, Ankara Numune Hastanesi, Turkey
Kirsten Tvede, Denmark
Naoki Uchiyama, Astellas Pharma inc, Japan
Alp Ucok, Sanofi Aventis Turkey, Turkey
Ýsmail Unal, Cukurova State Hospital, Turkey
Huseyin Unlu, Yunus Emre Devlet Hastanesi - Eskisehir, Turkey
Lutfu Ural, Janssen Cilag Turkey, Turkey
Bulent Uygur, Usak Devlet Hastanesi, Turkey
Banu N. Uzun, GSK Turkey, Turkey
Vasileiios Vagenas, Lundbeck Hellas, Greece
Maria Beatriz Valadares Santos, Janssen Cilag Portugal, Portugal
Eleni Valergaki, Lundbeck Hellas, Greece
Petar Valkanov, MBAL “Ivau Rilski” Psychiatric Practice, Bulgaria
Peter van Panhuis, NIFP, The Netherlands
Martin Lorenzo Vargas, Lundbeck España SA, Spain
Dilhan Varolgunes, Janssen Cilag Turkey, Turkey
Hatice Vedin, Santa Farma, Turkey
Evangelos Vergis, Lundbeck Hellas, Greece
Spyridon Vervainiotis, Galineio Malathron, Greece
Vesselina Vloeva -Slavcheva, OPDZ-Sofia, Bulgaria
Constantina Vrontou, Greece
Gang Wang, Beijing An Ding Hospital, China
Xueyi Wang, The First Hospital of Hebei Medical University, China
Tracy Warbrick, Kliniken der Heinrich-Heine Universitat Dusseldorf, Germany
Viktoria Weggeberg, Stavanger University Hospital, Psychiatric Clinic, Norway
Killian Welch, Edinburgh University, UK
Anne Kristine Wersland, Stavanger University Hospital, Norway
Sonny Surya Wibatsuh, Novartis Indonesia, Indonesia
Audun Wigestrand, Stavaner University Hospital, Norway
Kim Wolff, Institute of Psychiatry, UK
Sun Xueli, West China Medicine School, China
Mehmet Yahya Öztürk, Santa Farma, Turkey
Elif Gunes Yalcin, Janssen Cilag Turkey, Turkey
Hayriye Dilek Yalvaç Çitil, Menemen Devlet Hastanesi, Turkey
Kun Yang, The 3rd Hospital of Mianyang, China
Aslihan Yapici, Sanofi Aventis Turkey, Turkey
Setsuko Yasugawa, Yatsushirokousei Hospital, Japan
Ibrahim Yenigun, Schering Plough, Turkey
Dogan Yeþilbursa, Bakirkoy Ruh ve Sinir Hast, Turkey
Yan Yifeng, AstraZeneca (wuxi)Trading Co. Ltd, China
Emine Yilmaz, Janssen Cilag Turkey, Turkey
Yalcin Yilmaz, Santa Farma, Turkey
Jin-Sang Yoon, Chonnam National Medical School, Republic of Korea
Suelin Yoon, Institute of Psychiatry, King’s College London, UK
Allan H Young, Institute of Mental Health, Canada
Robyn Young, Connexions Clinic, Australia
Ferda Ýzgiç, Ýzmit Seka Devlet Hastanesi, Turkey
Tayfun Zeren, Bati Poliklingi, Turkey
Jinbei Zhang, 3rd Hospital of Sun Yat-Sen University, China
Kerang Zhang, The First Affiliated Hospital of Shanxi Medical University, China
Shaoping Zhang, Shanghai Hongkou Mental Health Center, China
Jingping Zhao, The Second Xiangya Hospital of Central South University, China
Lu Zheng, Shanghai Tongji Hospital of Tongji University, UK
Cai Zhuoji, Beijing Anding Hospital, P.R. China
Selma Bozkurt Zincir, Janssen Cilag Turkey, Turkey
Major Psychoses and Substance Abuse
109
MAp & key
Contents
Main Attractions
Key Conference Locations
1 Edinburgh Castle and Military Museums E5
41 Edinburgh International Conference Centre (EICC) D6
2 The Palace of Holyroodhouse H5
42 Caledonian Hilton, Princes Street D5
3 St Giles Cathedral F5
43 The Edinburgh Residence, Rothesay Terrace C5
4 Royal Museum of Scotland F6
44 The Bonham, Drumsheugh Gardens C5
5 Museum of Scotland F6
45 Channings Hotels, South Learmonth Gardens B4
6 Royal Botanic Garden D2
46 Grosvenor Hilton Edinburgh, Grosvenor Street C6
7 National Gallery of Scotland E5
47 Marriott Edinburgh, Glasgow Road A6
8 Royal Scottish Academy E5
48 Carlton Edinburgh, North Bridge F5
9 Scottish National Portrait Gallery F4
49 Holiday Inn Edinburgh, Corstorphine Road A6
10 City Art Centre F5
50 Holiday Inn Edinburgh North, Queensferry Road B4
11 Scottish National Gallery of Modern Art B5
51 Fountain Court Apartments, Morrison Street C6
12 Dean Gallery B5
52 Fountain Court Apartments, Grove Street C6
13 Dynamic Earth H5
14 Museum of Childhood G5
15 Scottish Whisky Heritage Centre E5
16 The Edinburgh Dungeon F5
35 Camera Obscura and World of Illusions E5
36 The Real Mary King’s Close F5
40 Scottish Parliament H5
110
Collegium Internationale Neuro-Psychopharmacologicum
43
46
51
44
52
41
42
48
47
49
50
45
Major Psychoses and Substance Abuse
111