1. health and fitness
2. disorders
3. mental disorder
4. depression

Psykiatriens 9. Forskningsdag
6. november 2014, AUH Risskov
AU
AARHUS
UNIVERSITET
Indhold Dagens program Side 3 Side 5 Side 7 Foredragsprogram Abstracts ‐ foredrag Posteroversigt Side 19 Abstracts ‐ posters Side 23 1 2 Dagens program 12:00 Sandwich i Vandrehallen og postervandring i Den Ny Festsal 13:00 Velkomst og introduktion til dagen ved professor Per Hove Thomsen i Auditoriet 13:15 Foredrag i Auditoriet 15:15 Kaffepause i Vandrehallen og postervandring i Den Ny Festsal 16:00 Foredrag i Auditoriet 17:00 Dommerkomiteen voterer 17:15 Taler – præmieoverrækkelse ved professor Per Hove Thomsen i Vandrehallen 17:30 Buffet i kantinen 18:30 Afslutning 3 4 Foredragsprogram Moderator: Poul Videbech 13.15 Jakob Linnet ‐ Forskningsklinikken for Ludomani, AUH Tre myter om dopamin og ludomani 14.00 Pause Moderatorer: Per Hove Thomsen og Ole Mors 14.15 Charlotte Ulrikka Rask ‐ Forskningsklinikken for Funktionelle Lidelser, AUH Helbredsangst hos unge ‐ association med helbredsproblemer og kontinuitet fra barndommen 14.30 Thao Phuong Tran ‐ Translational Neuropsychiatry Unit, AU Sammenhængen mellem inflammation og depression; et funktionelt og morfometrisk, longitudinelt PET/MRI‐studie baseret på en rottedepressionsmodel 14.45 Niels Okkels – Afdeling M, AUH Risskov En gennemgang af 10 års prægraduat forskning i psykiatri. 15.00 Anne‐Mette Lange – BUC, Risskov, Forskningsafsnittet De sociale og personlige omkostninger af ubehandlet ADHD hos voksne 15.15 Pause Moderatorer: Povl Munk‐Jørgensen og Gregers Wegener 16.00 Niklas W. Andersson ‐ Afdeling M, AUH Risskov Depression og risikoen for autoimmun sygdom: prospektive analyser på et landsdækkende repræsentativt sample 16.15 Søren Dinesen Østergaard – Afdeling P, AUH Risskov Klinisk og Psykometrisk validering af Psychotic Depression Assessment Scale 16.30 Christina Weide Fischer ‐ Translational Neuropsychiatry Unit, AU Kronisk inflammation i rotter: adfærd og systemiske adaptationer 16.45 Nicolai Ladegaard – Afdeling Q, AUH Risskov Prosodi hos deprimerede patienter 5 6 Abstracts Foredrag 7 8 The three fallacies of dopamine in gambling disorder Jakob Linnet Forskningsklinikken for Ludomani, Århus Universitetshospital Nørrebrogade 44, bygning 30 DK‐8000 Århus C. Ludomani er en afhængighedstilstand forbundet med dopaminerge dysfunktioner. Foredraget tager udgangspunkt i tre hypoteser om dopaminerge dysfunktioner i ludomani, som forekommer at være fejlslutninger. Den første hypotese antager, at personer med ludomani har lavere baseline bindingspotentiale, hvilket ofte ses ved stofmisbrug; den anden hypotese antager, at spilleaktivitet er forbundet med højere dopaminfrigivelse ved ludomani; den tredje hypotese antager, at gevinster er forbundet med højere dopaminfrigivelse ved ludomani. Det har ikke været muligt at finde belæg for disse hypoteser i positron emissions tomografi (PET) undersøgelser af dopaminfrigivelse ved ludomani. I stedet ser det ud til at dopaminerg kodning af usikkerhed bedre kan redegørelse for de dopaminerge dysfunktioner ved ludomani. Personer med ludomani lider muligvis af en "dobbelt belastningstilstand", hvor dopaminfrigivelse er forbundet med øget spænding, men dårligere problemløsningsadfærd. 9 Health anxiety in preadolescence ‐ concurrent health problems and longitudinal pathways in childhood Charlotte Ulrikka Rask1,2, Anja Munkholm3, Lars Clemmensen3, Martin K. Rimvall3, Eva Ørnbøl1, Pia Jeppesen3,4, Anne Mette Skovgaard5 1
The Research Clinic for Functional Disorders and Psychosomatics, AUH 2
Child and Adolescent Psychiatric Center Risskov, AUH 3
Child and Adolescent Mental Health Center, Mental Health Services, Glostrup 4
Faculty of Health Science, University of Copenhagen 5
Institute of Public Health, Faculty of Health Sciences, University of Copenhagen, Denmark. Objective Epidemiological data on the distribution, persistence and clinical correlates of health anxiety (HA) in childhood are scarce. This study investigated HAA‐symptoms and associated mental and somatic health problems and use of health services in primary care in a general population birth cohort. Method HA‐symptoms were examined in 11‐12 year‐old children (N=1886) from the Copenhagen Child Cohort by the Childhood Illness Attitude Scales (CIAS), together with socio‐demographic information, the child’s medical and mental status and health care utilisation. Regression analyses were used to compare groups with low (N=184), intermediate (N=1539) and high (N=161) HA‐symptom scores. The association between former assessed HA‐symptoms at age 5‐7 years and current HA‐symptoms at age 11‐12 years was examined by Stuart‐Maxwell test. Results HA‐symptoms were significantly associated with emotional disorders and unspecific somatic complaints (p‐values<.001) but not chronic medical conditions. In regression analyses controlling for gender and physical comorbidity children with the highest HA‐symptom score had the highest medical costs in primary care (p=0.027) where they used almost twice more health care than children with the lowest score during the two‐year period preceding inclusion. HA‐symptoms at age 5‐7 years significantly predicted high levels of HA‐symptoms at age 11‐12 years (p<.001). Conclusions Symptoms of HA including hypochondriacal fears and beliefs were non‐trivial in preadolescents as they showed continuity from early childhood and association with emotional disorders, unspecific physical complaints and increased health care costs. Further research of the clinical significance of HA in children is required. 10 Cognitive assessment of depressed rats; iPADs for rodents Thao Phuong Tran, Helle Lyng Christensen, Freja Bertelsen, Arne Møller and Ove Wiborg Translational Neuropsychiatry Unit, Dept of Clinical Medicine, Aarhus University Major depressive disorder (MDD) is a disabling disease associated with significant mortality and health cost. Some of the main symptoms of MDD are anhedonia (loss of general interest) and devastating cognitive impairments or distortions. To identify new therapeutic targets, the focus is on cognitive dysfunctions like: 1) a cognitive bias or selective preference for negative inputs 2) cognitive deficits, which include impairments in attention, short‐term memory and executive functioning. This project focuses on cognitive impairments associated with Chronic Mild Stress (CMS) induced anhedonia. After chronically exposure of rats to unpredictable stressors some of them will, like humans, become anhedonic, while others are able at coping and termed resilient. To assess the cognitive performance of the rats we use the Touch Screen Operant Platform which is highly similar to the human cognitive tests. One of the main tasks is Pairwise Discrimination (PD) learning and reversal. During the PD task, the rats are scored for their ability to acquire new associations (picture A=reward, picture B=punishment), functions known to depend upon the orbitofrontal region of prefrontal cortex and interconnected subcortical areas. After the task has been acquired, the rats have to do reversed learning (picture B=reward, picture A=punishment), addressing cognitive flexibility. With this project, we aim at getting new insights into cognitive impairments associated with stress‐induced depression. 11 Evaluating 10 years of pre‐graduate research in medicine and psychiatry Niels Okkels1,2,3, Marlene Skovgaard3,4, Mette Krogh Christensen5, Niklas Telinius6,7, Ellen‐Margrethe Hauge8 1
Department of Organic Psychiatric Disorders and Emergency Ward (Dept. M), Aarhus University Hospital, Risskov, Denmark. 2
Psychiatric Hospital Augustenborg, Hospital of Southern Jutland, Denmark. 3
Society for Medical Student Research, Aarhus University, Denmark. 4
Graduate School of Health, Faculty of Medicine, Aarhus University, Denmark. 5
Center for Medical Education, Aarhus University, Denmark. 6
Department of Biomedicine, Aarhus University, Denmark. 7
Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Skejby, Denmark. 8
Department of Rheumathology, Aarhus University Hospital, Denmark. Introduction
In Denmark, medical students can apply for an optional, one‐year, pre‐graduate research programme. The programme has existed for 25 years. However, little is known about the main quantitative outcomes; namely scientific publications and continuation to a PhD.‐programme. Also, little is known about the distribution of students between the medical specialties, including psychiatry. Method We included all medical students enrolled in the pre‐graduate research programme (n=687) from 2003‐2012 at Aarhus University, Denmark. We made a systematic literature search on the publications of a sub‐group of the students (n=227). Students were characterized in terms of age, sex, and years of medical school completed at the time of embarking the programme. Students affiliated with psychiatric departments (n=12) were characterized and compared with their peers. Results All together the 227 students published 224 papers. Of these, 90% were original articles and 43% had a student as first author. Fifty‐two percent published ≥1 papers. Twelve out of 687 students (2%) were enrolled at a psychiatric department. Of these, 1 student published 1 paper as second author and none continued in a PhD. Overall, publication was associated with (i) fast completion of the programme, (ii) having a male main supervisor and (iii) continuing to a PhD. Conclusion Scientific publishing and PhD.‐recruitment was associated with fast completion and early enrolment in the pre‐graduate research programme. A relatively low proportion of students were affiliated with psychiatric departments. 12 De sociale og personlige omkostninger af ubehandlet ADHD hos voksne Anne‐Mette Lange Aarhus University Hospital, Research Department, Centre for Child & Adolescent Psychiatry
Oplæget er baseret på undersøgelsen: The Private and Social Costs of ADHD: COST ANALYSIS By “CASA” – “Cost Analysis Study group for ADHD”: David Daley, Rasmus Højbjerg Jacobsen, Anne‐Mette Lange, Anders Sørensen, and Jeanette Walldorf. The Rockwool Foundation Research Unit Study Paper No. 69: 2014 Introduktion De samlede sociale og personlige økonomiske konsekvenser af ADHD har ikke hidtil været belyst. Tidligere undersøgelser har haft en række metodologiske begrænsninger, og været baseret på forsikringsdatabaser, og typisk taget udgangspunkt i omkostninger i forhold til sundhedsydelser. Ved brug af de danske registre er dette studie et forsøg på at opnå et estimat af de sociale og personlige omkostninger af ADHD hos voksne ved at sammenligne gruppen med en matched kontrol gruppe. Metode En gruppe af 1431 individer diagnosticeret med ADHD, uden anden ko‐morbiditet blev identificeret ud fra de danske registre. Gruppen blev sammenlignet på en række outcomes med en gruppe af søskende uden ADHD og komorbiditet. Resultater ADHD medførte signifikant større personlige omkostninger (lønindtægt og uddannelsesstatus) og sociale omkostninger (overførselsindkomster, manglende skatteindtægter, kriminalitet, trafikulykker, anbringelser, og sundhedsydelser) for gruppen af individer med ADHD sammenlignet med gruppen af søskende uden ADHD. Diskussion Resultaterne fremhæver den betydelige indvirkning, som ubehandlet ADHD har for voksne, både personligt og samfundsmæssigt. Konsekvenserne ved ubehandlet ADHD drøftes og konkrete tiltag for at nedbringe de høje omkostninger fremlægges. 13 Depression and the risk of autoimmune disease: A nationally representative, prospective longitudinal study Niklas W. Andersson Afdeling M, AUH Risskov Background Depression has been associated with various inflammatory‐related physical conditions, such cardiovascular and neurodegenerative diseases. Yet, little is known about the association between depression and autoimmune diseases (ADs). Objectives This study examined the association between depression and risk of AD, investigating the temporal and dose‐response nature of these relationships. Methods A prospective study including approximately 1.1 million people was conducted using linked Danish registries. 145,217 participants with depression were identified between 1995 and 2012. Survival analyses were used to estimate the relative risk of AD among those with, compared to without, depression. Analyses were adjusted for gender, age, and mental disorders. Results Depression was associated with increased risk of a wide range of ADs. One depressive episode was associated with 40% increased risk of any AD (IRR=1.40, 95% CI=1.31‐1.50), while having 4 or more depressive episodes showed a 112% increase in risk (IRR=2.12, 95% CI=1.01‐4.44) suggesting a dose‐response relationship. Results indicated a general increased risk of AD following the emergence of depression (during first year, IRR=1.29, 95% CI=1.05‐1.58, and persisting after 11 years or more IRR=1.53, 95% CI=1.34‐1.76). Conclusion Depression appears to be associated with increased risk of the onset of a range of ADs. The pattern of these associations is suggestive of a dose‐response relationship and the increased risk of ADs was not confined to a specific time period following the onset of depression. Depression may play a role in the etiology of certain autoimmune conditions. Further research is needed to validate and clarify present findings. 14 Clinical and Psychometric Validation of the Psychotic Depression Assessment Scale Østergaard SD, Pedersen CH, Uggerby P, Munk‐Jørgensen P, Rothschild AJ, Larsen JI, Gøtzsche C, Søndergaard MG, Bille AG, Bolwig TG, Larsen JK, Bech P Aarhus Universitetshospital, Risskov. Afdeling P. Background/Objectives Recent studies have indicated that the 11‐item Psychotic Depression Assessment Scale (PDAS), consisting of the 6‐item melancholia subscale (HAM‐D6) of the Hamilton Depression Rating Scale and 5 psychosis items from the Brief Psychiatric Rating Scale (BPRS), is a clinically valid, scalable (unidimensional), and responsive measure for the severity of unipolar psychotic depression (UPD). The aim of this study was to subject the PDAS, and its depression (HAM‐D6) and psychosis (BPRS5) subscales to further clinical and psychometric validation. Methods Patients with clinical diagnoses of UPD assigned at Danish psychiatric hospitals participated in semi‐structured interviews. Video recordings of these interviews were assessed by two experienced psychiatrists (global severity rating of psychotic depression, depressive symptoms and psychotic symptoms) and by two young physicians (rating on 27 symptom items, including the 11 PDAS items). The clinical validity of the PDAS and its subscales was investigated by Spearman correlation analysis of the global severity ratings and the PDAS, HAM‐D6, and BPRS5 total scores. The scalability of the scales was tested by Mokken analysis. Results Ratings from 39 subjects with unipolar psychotic depression and nine patients with bipolar psychotic depression were included in the analysis. The Spearman correlation analysis versus global severity ratings indicated that the PDAS, HAM‐
D6 and BPRS5 were clinically valid measures of both UPD and BPD. According to the Mokken analysis, the scales demonstrated acceptable scalability. Conclusions The clinical validity and scalability of the PDAS and its subscales, the HAM‐D6 and BPRS5, was confirmed in an independent sample. 15 Modelling chronic inflammation in rats: behaviour and whole body adaptations Christina W Fischer, Betina Elfving, Sten Lund and Gregers Wegener Translational Neuropsychiatry Unit, AU Background Inflammation is the body’s first defence system against infections, but exaggerated inflammatory processes may be involved in chronic diseases, ranging from depression to diabetes. Chronic inflammation affects the whole body, from brain function and behavioural adaptations to energy regulation. Objective In order to understand the underlying mechanisms, the aim of this study was to develop a model of chronic inflammation in rats. Specifically, we assessed: 1) behavioural changes, 2) cytokine levels in the brain and in blood, and 3) peripheral adaptations. Methods Sprague‐Dawley rats (n=60) were randomized to receive a single (20h) or chronic (eight weeks) treatment with either lipopolysaccharide (LPS, 600μg/kg, i.p.) or saline. Behavioural tests included: locomotor activity in an open field, and depressive‐like behaviour in the forced swim test. 24 cytokines were investigated using a multiplexing technology (Luminex xMAP) and the Bio‐Plex® 200 platform (Bio‐Rad Laboratories, USA) in serum, frontal cortex, and hypothalamus. Results and discussion Interestingly, chronic LPS treated rats displayed similar sickness behaviour (decreased appetite, low activity level and depressive‐like behaviour) as acute LPS treated rats. However, distinct chronic inflammatory responses were detected; elevated pro‐inflammatory cytokines (IL‐1β and IFN‐γ) in the brain, induced local tissue responses (hepatomegaly and decreased fat mass), and hyperglycemia. Surprisingly, no cytokine changes were observed in serum following chronic LPS treatment, indicating compartment specific responses. Conclusion Taken together, chronic LPS administration induced multiple local inflammatory responses and behavioural adaptions. A model of chronic inflammatory sequelae could elucidate molecular mechanism behind psychiatric symptoms and therefore aid in targeting treatment options. 16 Prosodi hos deprimerede patienter Nicolai Ladegaard Afdeling Q – Afdeling for Depression og Angst, AUH Risskov Affektive lidelser er en af tidens største sundhedsmæssige udfordringer. Forekomsten af affektive lidelser er høj og stigende. Diagnostik og monitorering af psykiske lidelser baseres på kvalitative vurdering af sundhedsfaglige professionelle. Nærværende forskningsprojekt arbejder hen imod at udvikle et elektronisk værktøj, der på baggrund af patienters talemønstre skal understøtte klinikerens vurdering af patientens status. Psykiske lidelser manifesterer sig typisk ved distinkte talemønstre. Optagelser at patienters stemmer behandles via state‐
of‐the‐art metoder inden for signalbehandling. Vha. maskinindlæringsteknikker vurderes symptomer og diagnoser automatisk baseret på små anomalier i talemønsteret (fx den tidslige struktur af tonelejet, pauser og talehastighed). Dette muliggør støtte til klinisk praksis (bl.a. tilbagefaldsforebyggelse) og klinisk forskning i de underliggende mekanismer ved psykiske lidelser. 17 18 Posteroversigt 19 20 21 22 Abstracts Posters 23 24 POSTER NR. 1 Probiotic treatment has anti‐depressant effect independent of diet Anders Abildgaard1,2, Gregers Wegener1, Marianne Hokland3 & Sten Lund2 1
Translational Neuropsychiatry Unit, Aarhus University (Risskov) Medical Dept. MEA, Aarhus University Hospital (Nørrebrogade) 3
Dept. of Biomedicine, Aarhus University 2
Background The literature suggests a bi‐directional association between metabolic disorders (type 2‐diabetes, metabolic syndrome) and depressive disorder. The gut microbiota may play an important role in both disease entities, and diet is known to alter the gut microbiota composition. Aim Considering the likely existence of a gut‐brain axis, does probiotic treatment affect glucose metabolism, depressive‐like behaviour or memory in healthy rats? May probiotic treatment protect against the adverse effects of a high‐fat diet? Methods 40 male Sprague‐Dawley rats were fed a high‐fat or control diet for 10 weeks. Additionally, a probiotic mix (8 lactobacillus/bifidobacteria species) or placebo were administered daily during the last 5 weeks. The animals were subjected to behavioural as well as metabolic tests. Furthermore, cytokine production from anti‐CD3/28 stimulated blood lymphocytes was measured. Results Independent of diet, probiotic treatment was associated with a marked reduction in depressive‐like behaviour, but it did not affect memory. Consumption of high‐fat diet led to increased body weight as well as increased glucose and insulin levels during an oral glucose tolerance test, but probiotic treatment did not affect these measures. Final analyses are still ongoing. Discussion Our findings add perspective to the potentially important role of the gut‐brain axis and clearly supports the novel concept of “psychobiotics”. Indeed, the probiotics used in this study should also be validated in a depression model. Nevertheless, our study lends inspiration to further studies into the involved pathophysiological mechanisms. 25 POSTER NR. 2 Betydningen af moderens vægt for forekomsten af ADHD og autisme hos børn Christina Hebsgaard Andersen Børne‐ og Ungdomspsykiatrisk Center, Risskov. Attention deficit hyperactivity disorder (ADHD) og autisme spektrum forstyrrelser (autisme) er neuropsykiatriske lidelser, som viser sig i barndommen med alvorlige følger for de ramte børn og deres forældre. Årsagerne til ADHD og autisme er ikke klarlagt, men der menes at være en væsentlig genetisk komponent i lidelserne sandsynligvis i kombination med miljøpåvirkninger. Blandt de miljøpåvirkninger, som er blevet diskuteret, er moderens vægt og vægtstigning. Der er muligvis en sammenhæng mellem moderens vægt i forbindelse med graviditeten og udviklingen af ADHD og autisme hos børnene. Der foreligger en række studier, som viser forskellige resultater, og der er fremsat teorier om årsagssammenhænge i relation til hormonforstyrrelser. I Danmark findes en af de største fødselskohorter i verden med ca. 100.000 deltagere, Bedre Sundhed for Mor og Barn, hvor bl.a. oplysninger om moderens vægt i forbindelse med graviditeten er indsamlet. Børnene i kohorten er i dag mellem 11 og 16 år, og via de danske registre er det muligt at identificere de børn, som er blevet diagnosticeret med ADHD eller autisme. En undersøgelse i kohorten af sammenhængene mellem moderens vægt i forbindelse med graviditeten og senere ADHD eller autisme hos barnet, vil være et unikt studie pga. størrelsen og kvaliteten af de indsamlede data, og det vil kunne tilføre afgørende nyt til den internationale søgen efter årsager til ADHD og autisme. 26 POSTER NR. 3 Depression and the risk of severe infections: prospective analyses on a nationwide representative sample. Niklas W. Andersson Afdeling M, AUH Risskov Objective Depression is linked with physical health. Preliminary research suggests an association between depression and subsequent increased risk of infections, yet little is known on this topic. This study investigated the association between depression and risk of various types of infections, including dose‐response and temporal relations. Methods A historical prospective population‐based study including 976,398 participants, of whom 142,169 had a history of depression between 1995 and 2012, was conducted using linked Danish registries. Survival analyses were used to estimate the relative risk of infections among those with, compared to those without, depression while adjusting for gender and age. Results Depression was associated with increased risk of a wide range of infections (IRR=1.61, 95% CI=1.49‐1.74, for any infection). In dose‐response analysis: the risk of infection was IRR=1.57, 95% CI=1.45‐1.75 at a single depressive episode and IRR=1.97, 95% CI=0.92‐4.22 if having experienced 4 or more depressive episodes. However, only few cases contributed to the analysis on more than 2 depressive episodes and results did not indicate a perfect linear association. There was little evidence of a specific temporal effect but rather a general increased risk of infection subsequent to the onset of depression. Conclusion Present findings suggest the presence of depression may confer increased risk of infection, and that this increased susceptibility is not confined to a discrete time period following the onset of depression. A dose‐response relationship may be present but further research is needed to further examine and to support the herein presented additional physical health consequences of depression. 27 POSTER NR. 4 Ketamine and Neuronal Plasticity of Hippocampus Maryam Ardalan1,2, Gregers Wegener2,3, Torsten M. Madsen4, Jens R. Nyengaard1 1. Stereology and Electron Microscopy Laboratory, Aarhus University Hospital, Aarhus, Denmark 2. Translational Neuropsychiatry Unit, Aarhus University Hospital, Risskov, Denmark 3. Pharmaceutical Research Center of Excellence, School of Pharmacy (Pharmacology), North‐West University, Potchefstroom, South Africa 4. Lundbeck A/S, International Clinical Research, Valby, Denmark Background & Aim Depressive disorders are common, serious and associated with enormous morbidity. In this study, design‐unbiased stereological methods are used to test the “neuronal plasticity hypothesis” in rat brain hippocampus as one of the main underlying mechanisms for anti‐depressive effects of the drug Ketamine. The “neuronal plasticity hypothesis” describes structural and functional plasticity and cellular resilience. This includes the promotion of dendritic growth, axonal sprouting, increased neurogenesis, synaptic remodeling, and new synaptic connections within specific brain regions. Material & method After ketamine injection and perfusion fixation of the rat brains, hippocampus is isolated, straightened out and embedded in 5% agar. The straightened hippocampus is sectioned perpendicular to its longest axis at 65‐μm thickness on a vibratome. Two sets of sections are chosen based on a systematic sampling principle and a section sampling fraction of 1/12. There are 8‐9 sections in each of the two sets. For examining synaptogenesis in stratum radiatum of CA1 ‐ subregion of hippocampus, the length of CA1 stratum pyramidale is measured along the CA2‐subicular (CA2‐SUB) axis at light microscopy and used as a 1D sampling guide. By use of the physical disector and electron microscopy the numerical density of synapses is estimated. We will divide asymmetric synapses in two spine and shaft synapses. The volume of different subfields of hippocampus is estimated by point counting using the Cavalieri estimator at light microscopy. 28 POSTER NR. 5 Toxoplasma gondii seropositvity is positively associated with anxiety and burnout‐syndrome Cecilie Bay‐Richter Translational Neuropsychiatry Unit, AU Toxoplasma gondii (TOX) is a common parasite affecting approximately one‐third of the human population, primarily targeting neurons and causing neuroinflammation. An increasing number of studies are providing evidence that the disease is associated with behavioural changes and psychiatric disease. The objective of this study is to examine TOX seropositivity in a large human population in relation to psychiatric symptoms. A population of 548 participants was initially included and the participants went through a semi‐structured diagnostic interview (SCAN interview) followed by blood sampling. From this population, a control group (n=158) with no diagnosis of psychiatric disorders was extracted as well as a group consisting of subjects showing symptoms of anxiety (n=106) and burnout syndrome (n=51). Blood serum was examined for IgG antibodies to TOX using ELISA assays. Data were analysed using logistic regression models and show that seropositivity of TOX is positively associated with anxiety (adjusted odds ratio [OR]=2.05; 95% CI, 1.14‐3.70; p=0.016). In addition, we find an association between seropositivity and burnout syndrome (OR=3.43; 95% CI, 1.67‐7.05; p<0.001). These data supports the notion that TOX is associated with psychiatric disorders. Our results are consistent with previous reports on an association between TOX and anxiety. Furthermore, we show a positive association between TOX seropositivity and the stress related syndrome, burnout syndrome. 29 POSTER NR. 6 Psychopharmacological treatment patterns of bipolar disorder in Denmark Louise Bjørklund Forskningsenhed P, Aarhus Universitetshospital, Risskov The pharmacological treatment of bipolar disorder is complex and often a lifelong effort. This is due to the fact that the treatment depends on the state of the patient (mania, depression, mixed episode) and also because around 90 % of the patients need co‐prescribing. Antidepressants are used in the treatment of more than half of the Danish patients with bipolar disorder, but not always in conjunction with an antimanic agent, as recommended. It involves a risk of clinical worsening. The aim of the study is to investigate the psychopharmacological treatment patterns of bipolar disorder in Denmark in order to compare treatment patterns with Danish and International guidelines, and to document the consequences of antidepressant use in bipolar disorder with and without concomitant mood stabilizer. Some of the possible consequences to investigate are the risk of affective switching (switch from depression to mania), the risk of suicide and the risk of development of mixed states. The study population consists of all Danish residents treated for bipolar disorder, outpatient or during hospitalization, between 1995 and 2013. These people are identified by the Danish Psychiatric Central Research Register where they are registered with an ICD‐8/ICD‐10 diagnosis of bipolar disorder. The prescription database provides information about the pharmacological use. Potentially, the study will results in better pharmacological treatment of bipolar disorder in Denmark by supporting guidelines with concrete knowledge within the area. 30 POSTER NR. 7 Chronic mild stress exposure induces the depression‐like symptoms in rats and attenuates EDHF‐like component of endothelium dependent relaxation Elena Bouzinova Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University Cardiovascular diseases have high co‐morbidity with major depression. In the chronic mild stress (CMS) model of depression rats are exposed to chronic unpredictable mild stressors. However, only some rats develop depression‐like symptoms (including ‘anhedonia’ which is measured as a reduction in sucrose intake), while others are stress‐resistant (‘resilient’). In the current study, anhedonic rats reduced their sucrose intake after 8 weeks of CMS by 55±7% while the resilient rats did not change their sucrose consumption compared with the baseline ntake. We analyzed endothelium‐
dependent relaxation of isolated mesenteric small arteries from non‐stressed, anhedonic, and resilient rats under isometric conditions. There was no difference in acetylcholine‐induced relaxation of noradrenaline pre‐constricted arteries from different groups under control (inhibitors free) conditions. L‐NAME treatment revealed an elevated NO‐
dependent relaxation in arteries from anhedonic rats. Accordingly, eNOS expression was increased in anhedonic group. Selective inhibition of COX‐1 with SC560 revealed similar COX‐1‐dependent contraction in the three groups. NS398, a selective COX‐2 inhibitor, suppressed relaxation stronger in arteries from anhedonic rats. No difference in the expression of COX1 and COX2 was found. Finally, endothelium‐dependent hyperpolarization (EDH) component of relaxation, sensitive to inhibition by apamin and TRAM, was significantly reduced in anhedonic rats. This was associated with a significant reduction in the expression of intermittent‐conduction K+ channels. Conclusions Our findings demonstrate that depression‐like symptoms are associated with reduced EDH‐like relaxation and elevated significance of NO‐ and COX‐2‐dependent signals in rat mesenteric arteries. These changes in endothelial function could affect peripheral resistance and organ perfusion in major depression. 31 POSTER NR. 8 Neurotrophic Factors in Depression in Response to Treatment Henriette N Buttenschøn1,2, Leslie Foldager1,2,3,4, Betina Elfving1, Pia H P Poulsen1, Rudolf Uher5,6, Ole Mors2,7 1 Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Denmark 2
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark 3
Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark 4
Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark 5
Kings College London, England 6
Department of Psychiatry, Halifax, Canada 7
Research Department P, Aarhus University Hospital, Risskov, Denmark Background Brain‐derived neurotrophic factor (BDNF) and vascular endothelial growth factor A (VEGF) have been suggested a pathophysiological role in depression. The aim of the present study was to investigate the longitudinal associations between depression scores and serum levels of BDNF and VEGF during antidepressant treatment. Potential predictors (including genetic polymorphisms) of baseline depression scores were likewise investigated. Methods The serum levels of BDNF and VEGF were measured at baseline and after 8 and 12 weeks of antidepressant treatment in 90 individuals with depression of at least moderate severity and allocated to treatment with either nortriptyline or escitalopram. Results Changes in depression score over time were not associated to changes in neither BDNF nor VEGF serum levels during the 12‐week treatment period. We observed a positive correlation between serum BDNF and VEGF levels and a significant decrease in the depression score during the treatment period. Serum BDNF and VEGF levels also decreased during the treatment period. We were not able to predict the severity of depression at baseline by serum levels of BDNF or VEGF, but observed a significant association between the Val66Met polymorphism (RS6265) in BDNF and BDI depression score at baseline. Individuals homozygous for methionine had a significantly higher BDI depression score. Discussion The present study is one of the most comprehensive studies of changes in serum VEGF and BDNF levels in response to antidepressant treatment. However, future larger studies are warranted. 32 POSTER NR. 9 Hippocampus in depression: a postmortem stereological study of hippocampal volume and cell number Fenghua Chen1,2, Raben Rosenberg1, Jens R. Nyengaard2,3, Karl‐Anton Dorph‐Petersen1,3,4 4
1Translational Neuropsychiatry Unit, Aarhus University 2Stereology and Electron Microscopy Laboratory, Aarhus University Hospital, Nørrebrogade 3Center for Stochastic Geometry and Advanced Bioimaging, Aarhus University Translational Neuroscience Program, Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA Substantial evidence suggests that structural plasticity in the hippocampus may play an important role in the pathophysiology of depression and its treatment. Also, in vivo imaging studies indicate that the volume of hippocampus may be reduced in depression. In the present study we search for cellular correlates to these findings. To address this question, we use stereological techniques to analyze postmortem brain samples. Hence, we investigate if prolonged and severe depression is associated with reduced volume of the hippocampal formation and changes in the numbers of neurons and glial cells in the different subregions of the hippocampus. In order to test the specificity of the potential findings we also include tissue from two additional subject groups: depressed suicide victims, and subjects with schizophrenia, respectively. Thus, the current study is based on hippocampi from four groups of subjects matched according to sex and age: 1) Unipolar depression, 2) Schizophrenia, 3) Suicide with a history of depressive disorder, 4) Control subjects with no history of psychiatric or neurological diseases. The microscopic analysis is based on state of the art stereological techniques: Cavalieri’s estimator is used to estimate the volume of hippocampus and its subregions, and the optical fractionator method is used to estimate the total number of neurons and glial cells in the individual cell layers in five main regions of hippocampus: the granular cell layer, hilus, CA2/3, CA1 and subiculum. We hope our results can provide a better understanding of the pathophysiology of depression and help developing new strategies for treatment. 33 POSTER NR. 10 Cognitive and social behavioral characterization of chronic mild stressed rats; a model of depression Simone Krog Christensen, Thao Phuong Tran, Lena Martis and Ove Wiborg Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Denmark. Major depressive disorder (MDD) is a disease affecting the everyday life of approximately 350 million people worldwide. Symptoms of depression includes anhedonia (loss of general interest) and decreases normal cognitive function of the individuals by causing impairments to attention, working memory, psychomotor and psychosocial processing. The recovery process of depression is therefore extensive and only about 60% of patients benefit from the present medical treatment which makes the discovery of new, alternative ways of treatment necessary. The aim of the present study want to characterize the phenotype and assess cognitive abilities of the Long Evans rat after exposure to the chronic Mild Stress Model of depression, to evaluate the use of this pigmented phenotype in further investigations of depression. In this study, we will use the CMS model to induce anhedonia in male Long Evans rats. The level of anhedonia is assessed using the sucrose consumption test. To assess cognition we use the Bussey‐Saksida Touch Screen Chamber paradigm and for further behavioral characterization we use the y‐maze, open field, elevated plus maze and social interaction behavioral tests. We expect this study to provide us with new insight into cognitive impairments in rats suffering from depression‐like condition induced by CMS. Such information could provide us with a translational model which could increase our understanding of the mechanisms underlying MDD and thus enhance the possibilities of finding new ways of treatment. 34 POSTER NR. 11 Disturbances of Circadian Rhythms in a Rat Chronic Mild Stress Model of Depression
S. L. Christiansen1, K. Højgaard1, E.V. Bouzinova1, J. Fahrenkrug2, O. Wiborg1 1
Department of Clinical Medicine, Aarhus University, Denmark Department of Clinical Biochemistry, Bispebjerg Hospital, Denmark 2
Clinical data from depressed individuals shows that physiological states and mood changes are consistent with disturbances in circadian related processes. The suprachiasmatic nucleus (SCN) is well known for its function as the master clock and regulates several circadian systems by clock genes expression. In addition to central expression, peripheral clock genes have been found. The study is based on a highly validated animal model of depression, the chronic mild stress (CMS) model. 8 depression‐
like rats and 8 control rats were killed by decapitation every 4 h within a 24 h period. Trunk blood, brain and liver tissue were collected. Core body temperature was measured with a rectal probe prior to blood collection. The amount of plasma corticosterone and melatonin were quantified using an ELISA and RIA kit, respectively. Identification of specific clock genes in the liver was done using the q‐PCR method. Quantification and visualization of clock genes in the brain were established by the in situ hybridization method. We studied three of the most essential clock genes, Per1, Per2 and Bmal1, and found that the effect of CMS on clock gene expression was selective and region specific. However, the SCN was partly protected against stress. We found an increased level of corticosterone and melatonin in the depression‐like animals as well as a shifted circadian rhythm. Further, CMS did not abolish the circadian rhythm of the phase markers, but induced shifts in peak levels for melatonin and core body temperature and induced an additional corticosterone peak. 35 POSTER NR. 12 Does screening for motivation and ability to change using behavioural analysis affect group cognitive behaviour therapy treatment‐outcome in bulimia nervosa patients? Loa Clausen 2, Allan Jones1, Kristian Rokkedal3 1
Institut for Psykologi, Syddansk Universitet, Odense Research Department and Eating Disorder Centre, Centre for Child and Adolescent Psychiatry, Risskov, Denmark 2
3
Background Recent evidence suggests that verbal indices of motivation to change (cognitive/verbal analysis) do not necessarily equate to actual change in response to treatment for an eating disorder if the patient does not also have the ability to change. In the present study we evaluate a motivation and ability to change screening procedure in determining readiness in bulimia nervosa patients to enter into cognitive behaviour therapy. Methods Treatment outcome was compared between patients for whom motivation and ability to change eating behaviour was verified prior to treatment (N = 78), and patients who were not screened (N = 205). Results Significant reductions on all bulimic symptoms for all patients were observed. Abstinence rates for bingeing and purging were higher in the group screened for motivation compared to the group not screened. However, the two groups did not differ significantly in the degree of symptom reduction. Conclusion Cognitive behaviour therapy was found to be an effective treatment for bulimia nervosa regardless of whether patients were screened for motivation and ability to change prior to treatment. Screening for motivation and ability to change may have an overall effect on symptom outcome, and these effects may be due to the early detection and deferment of patients not yet at the stage of readiness to benefit from psychotherapy. 36 POSTER NR. 13 Eating Disorder Examination ‐ Differences in eating disorder pathology between men and women with eating disorders Maja Koefoed1, Kristian Rokkedal1, Loa Clausen 2 1
Eating Disorder Centre and 2Research Department, Centre for Child and Adolescent Psychiatry, Risskov, Denmark Background In general eating disorder pathology in men shows more similarities than differences compared to women, however, with an overall lower level of pathology. In community studies men have been found to have more excessive exercise and more binge eating and in a clinical population men have been found to have more vomiting. Analysis of women and men’s score on the interview defines as the golden standard of diagnostic assessment i.e. Eating Disorder Examination (EDE) have never been reported. Methods Cross sectional analysis of all children, adolescents and adults referred to treatment at The Eating Disorder Centre, Risskov 1997 ‐ 2013 who fulfilled criteria for an eating disorder according to DSM‐5. Results 2213 patients (80 men and 2133 women) were referred for treatment and 1944 (69 men and 1875 women) were included for analysis. 49.3% of men vs. 40.5% of women fulfilled criteria for anorexia nervosa, 18.8% of men vs. 31.8% fulfilled criteria for bulimia nervosa, and 31.9% of men vs. 27.7% of women had an atypical eating disorder. Differences between sexes were found on all subscales of the EDE however with some subdiagnostic differences. Differences were also found on the proportion of patients with binging and purging. Conclusion The study confirms earlier studies showing a tendency of men showing less eating disorder pathology on general eating disorder assessment instruments. When using EDE in research and clinic awareness on men and women’s different scores are needed. 37 POSTER NR. 14 Teletræning til psykiatriske patienter Birgit Linnet Clemmensen Fysioterapien, MA5, AUH Risskov Projektet var et innovationsprojekt. Projektet blev udviklet et samarbejde mellem Fysioterapien, MA5 og BUC/OPUS. Formålet med projektet var at undersøge om en specialudviklet træningsapplikation kan motivere og støtte psykiatriske patienter i at fastholde eller øge deres fysiske aktivitetsniveau i hverdagen med henblik på at forebygge livsstilssygdomme og tidlig død. Appen blev udviklet sammen med 23 patienter. De inkluderede patienter var mellem 15 og 34 år, og led af skizofreni (20) unipolar depression (2) eller bipolar sindslidelse (1). Innovationsprojektet løb fra den 15.april til den 15.oktober 2013. Evalueringen afsluttedes primo 2014. Evalueringen bestod af kvalitative interviews af de inkluderede patienter (21). 2 af deltagerne fik ikke lavet slutevaluering. Fokusgruppeinterview af projektfysioterapeuterne (4). Indsamling og behandling af kvantitative data, som løbende blev registreret på Træningsapplikationen. Projektets hovedresultater viste: •
At Træningsapplikationen havde en positiv indflydelse på hovedparten af de inkluderede patienters motivation til at være fysisk aktiv. Alle patienter øgede (20) eller vedligeholdte(1) deres fysiske aktivitets niveau under den kliniske pilotfase. •
At teletræning kunne benyttes som behandlingsredskab til patienter, som enten ikke er i stand til at få konventionel behandling på grund af manglende personlige ressourcer og/eller geografiske afstande. •
At brug af Træningsapplikationens og den løbende kontakt denne kan give mulighed for, i nogle situationer kan supplere og/eller erstatte dele af den konventionelle behandling, når det primær mål er at understøtte og motiverer til fysisk aktivitet. Efter projektevalueringen er der bevilliget penge til videreudvikling af en større platform bestående af flere applikationer herunder en "Fys. app" som kan støtte op om fysisk aktivitet til psykiatriske patienter. 38 POSTER NR. 15 Analysis of minicolumnarity in Human Cerebral Cortex Ali H. Rafati1,2,3, Farzaneh Safavimanesh2,4, Karl‐Anton Dorph‐Petersen2,3,5, Jakob G. Rasmussen2,4, Jesper Møller2,4, Jens R. Nyengaard1,2 1
Stereology and Electron Microscopy Laboratory, Department of Clinical Medicine, Aarhus University 2
Centre for Stochastic Geometry and Advanced Bioimaging (CSGB), Aarhus University 3
Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University 4
Department of Mathematical Sciences, Aalborg University 5
Translational Neuroscience Program, Department of Psychiatry, University of Pittsburgh Background Cortical minicolumns are hypothesized to be the basic cellular organization of the human cerebral cortex which may be changed in various psychiatric diseases. However, the mere existence of minicolumns and the methods to detect or quantify these in human cerebral cortex have long been subject to discussions. Current methods for studies of minicolumns are based on two dimensional (2D) image analysis of thin sections. The main drawback of these techniques is that they are model based, i.e. they a priori assume the existence of well‐defined 3D minicolumns. In contrast to 2D image techniques, modern quantitative light microscopy methods make it possible to register 3D coordinates of cells. These 3D data are suited to test the hypothesis whether minicolumns exist or not. Material and Method We used small tissue blocks from two human brains corresponding to Brodmann area 4 (BA4). BA4 is easily recognizable due to the large Betz cells in layer five, and a cortical area expected to have distinct minicolumns. Data was collected on a stereological microscope system in 140‐µm‐thick glycol methacrylate sections as x‐, y‐, z‐coordinates for pyramidal neurons and nonpyramidal neurons in cortical layer III. We searched for indication of a columnar 3D pattern in the neuronal positions with classical summary statistics (L‐ and G‐functions), Delaunay edge method and the newly developed cylindrical K‐function. The results were compared to results from two models: a homogeneous Poisson process exhibiting complete spatial randomness (CSR) and a Poisson line cluster point process (PLCPP). Results The data shows in three out of four samples non‐random patterns in the 3D neuronal positions with the direction of minicolumns perpendicular to the pial surface of the brain ‐ without a priori assuming the existence of minicolumns. Thus, a clear difference from CSR in the data could be detected with our new tool, the cylindrical K‐function, in contrast to the classical functional summary statistics which are less useful in this regard. Conclusion We have been able to detect patterns in 3D which are in agreement with the existence of minicolumns. Also, we have developed a graphical method for the assessment of columnarity in a brain area. 39 POSTER NR. 16 Schizophrenia‐associated alterations of microtubule associated protein 2 in human auditory cortex Micah A. Shelton1,2, Jason T. Newman2, Ken N. Fish1,2, Karl‐Anton Dorph‐Petersen1,4,5, Peter Penzes6,7, David A. Lewis1,2, Robert A. Sweet 1,2,3,8 1
Translational Neuroscience Program, Departments of 2Psychiatry, and 3Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA Translational Neuropsychiatry Unit, Department of Clinical Medicine, 5Centre for Stochastic Geometry and Advanced Bioimaging, Aarhus University, Aarhus, Denmark 6
Department of Physiology, 7Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL 8
Mental Illness Research, Education, and Clinical Center, VA Pittsburgh Healthcare System, Pittsburgh, PA 4
Background Laminar‐specific reductions in dendritic spine density in the primary auditory cortex (PAC) and other cortical regions is part of the pathology of schizophrenia (SZ). These findings are suggesting functional alterations in the proteins responsible for maintenance of dendritic spine architecture. Microtubule‐associated protein 2 (MAP2) is crucial for establishing and maintaining both dendrite and spine structure in response to changes in neural activity. A decrease in MAP2 immunoreactivity (IR) has been reported in several areas in SZ. Therefore, we hypothesized a role for MAP2 in reduced dendritic spine density in the PAC. Methods We used quantitative fluorescence microscopy coupled with immunohistochemical markers for dendritic spines and MAP2 to examined MAP2‐IR and dendritic spine density in human post‐mortem tissue from the PAC of individuals with SZ and matched controls. Results MAP2‐IR based on an antibody targeting the protein’s c‐terminal microtubule binding domain was significantly (p<0.05) reduced in SZ, with 60% of SZ subjects exhibiting fluorescence values near background, below the lowest values observed in controls. Reductions in dendritic spine density were restricted to those SZ subjects with reduced MAP2‐IR. Restoration of MAP2‐IR was achieved through antigen retrieval. As well, MAP2‐IR was detected through the use of antibodies targeting alternate epitopes along the protein. Thus, we hypothesize that the decrease in MAP2‐IR is due to a disease specific post‐translational effect that masks the c‐terminal epitope targeted by our antibody. Conclusions and Future Directions We observed a disease‐associated altered MAP2‐IR and the changes are correlated with dendritic spine loss in these subjects. Using a combination of quantitative microscopy, antibody‐based epitope mapping, and targeted proteomics, we will generate total and domain specific measures of MAP2 to determine how changes in protein levels and epitope availability contribute to the loss of MAP2‐IR in SZ. Liquid chromatography‐mass spectrometry will be used in an effort to elucidate post‐translational modifications as well as atypical protein interactions which could mask recognition of the c‐
terminal epitope. 40 POSTER NR. 17 Ketamine’s antidepressant‐like activity relies on a serotonin‐dependent mechanism in a genetic rat model of depression Kristian Gaarn du Jardin1, Nico Liebenberg1, Heidi Müller1, Connie Sanchez2, Betina Elfving1, Gregers Wegener1 1
Translational Neuropsychiatry Unit, Aarhus University, Skovagervej 2, 8240 Risskov, Denmark 2
External Sourcing, Lundbeck Research USA, Inc., 215 College Rd, Paramus, NJ 07652, USA Current first‐line treatment of clinical depression usually has a delayed therapeutic effect of several weeks, which calls for the development of antidepressants with a more rapid onset of action. An intravenous infusion of ketamine produces an antidepressant effect within two hours that persists for more than one week in otherwise treatment‐resistant patients. Ketamine is an antagonist at the NMDA receptor of the glutamate neurotransmitter system, but the mechanisms mediating its antidepressant effects remains largely unknown. Moreover, ketamine is associated with serious side effects and is consequently unsuited for widespread clinical use. Identification of mechanisms associated with rapid antidepressant effects may therefore prove pivotal. Consistent with clinical findings, ketamine exhibits a rapid and sustained antidepressant‐like effect in a genetic model of depression, Flinders Sensitive Line (FSL) rats, and studies in this model may offer opportunities to gain new mechanistic insights. Furthermore, numerous publications support that the neurotransmitter serotonin is implicated in antidepressant responsiveness. Here we investigate the impact of brain serotonin levels on ketamine’s antidepressant‐
like effect in the forced swim test (assessment of behavioral despair in rodents). In detail, the effect of acute ketamine treatment was assessed in FSL rats with normal serotonin levels and serotonin‐depleted rats treated with p‐
chlorophenylalanine. FSL rats exhibited similar depressive‐like phenotypes under normal and low serotonin levels. At normal levels, ketamine had rapid and sustained antidepressant‐like effects. However, both effects were abolished in serotonin‐depleted rats, indicating a critical role of brain serotonin for these effects in FSL rats. The serotoninergic mechanism involved remains to be identified. 41 POSTER NR. 18 Grundforskning i kliniske rammer ‐ Inspiration til forskning med translationelle perspektiver Heidi Müller & Betina Elfving Translational Neuropsychiatry Unit, AU Translationelle studier er essentielle i jagten på nye og bedre psykofarmaka samt patofysiologiske biomarkører. Fundamentet i vores forskning, der primært er centreret omkring depression, er humane blodprøver samt blod og væv fra rottemodeller. I laboratoriet har vi, baseret på vores mange års erfaring samt farmakologiske, biokemiske og molekylærbiologiske baggrund, etableret en række teknikker, der muliggør målinger på RNA og protein niveau af diverse analytter på blod og hjernevæv. Teknikkerne er i dag strømlinet, således at større projekter uden problemer kan håndteres og troværdige/reproducerbare resultater opnås. Teknikkerne, der i dag udgør grundpillen i vores forskning, er: Real‐time qPCR, subcellulær fraktionering (separation af eksempelvis gliaceller/synaptosomer, præ/postsynaptisk neuroner), superfusion (frigivelse af neurotransmitter), molekylærbiologiske studier (Immuno blotting, binding/optag, ELISA), samt multiplexing vha vores Luminex system. Luminex multiplex teknologien muliggør detektion og kvantifikation af op til 100 analytter i 50 µl prøve. 42 POSTER NR. 19 Patientstyrede indlæggelser i psykiatrien ‐ en national eksplorativ og teorigenerende undersøgelse af ’Brugerstyrede senge’ Ellegaard, T. Aarhus Universitetshospital Risskov, Afdeling for psykoser ‐ Forskningsenhed P
Baggrund Mere og bedre involvering af patienter, kan øge sundhedsydelsernes faglige og patientoplevede kvalitet og forbedre sundhedsvæsenets effektivitet. Patientstyrede indlæggelser (PSI) er et nyt tiltag til at organisere psykiatrien og involvere patienterne. Udvalgte patienter tilbydes kontrakt på selv at kunne initiere en kort indlæggelse på psykiatrisk hospital. I Danmark har man på forsøgsbasis indført i alt 21 brugerstyrede senge, fordelt på psykiatriske hospitaler i de fem regioner. PSI er indtil nu kun afprøvet i Norge. Her viser interviewstudier, at PSI giver patienterne kontrol og en følelse af tryghed, hvor de oplever at få hjælp før symptomforværring (BEGGE) og patienter synes at anvende flere aktive strategier til at håndtere deres sygdom (RCT). Et spejlstudie viser, at de samlende antal indlæggelsesdage faldt med 33 % og antallet af dage, patienter var underlagt tvang, blev næsten halveret. Formål At beskrive patienter og sundhedsprofessionelles erfaringer med PSI samt at udvikle en empirisk funderet forklaringsmodel over de væsentligste komponenter og virkningsmekanismer ved PSI som metode. Desuden at beskrive patienterne, som bruger PSI og årsager hertil. Metode Projektet indeholder 3 delstudier, der er komplementære eksplorative studier, men er ikke integreret i hinanden. Delstudie 1 & 2: Grounded theory studie med fokusgrupper, interviews og deltagerobservation med patienter (1) og sundhedsprofessionelle (2) omhandlende deres erfaringer med PSI. Delstudie 3: Eksplorativ spørgeskemaundersøgelse blandt patienter og personale. 43 POSTER NR. 20 Altered tryptophan metabolism in a genetic rat model of depression. Amanda Eskelund, David P Budac, Betina Elfving, Connie Sanchez & Gregers Wegener. Translational Neuropsychiatry Unit. AU Depression is a highly prevalent disease with heterogenous symptoms and subsequently, the pathomechanisms difficult to unravel. Several studies have previously linked depression to changes in tryptophan metabolites (TRYMETs) including serotonergic and glutamatergic dysregulation to stress‐ and inflammation‐induced depression. However, these studies have often focused on a subset of metabolites where a larger picture could provide valuable information on the underlying pathophysiology. Thus, we sought to map 13 TRYMETs, encompassing both the serotonergic and kynurenine pathways, in our rodent, genetic model of depression using liquid chromatography‐tandem mass spectrometry (LC‐
MS/MS). Female, 12‐20 weeks old, depressive‐like flinders sensitive line (FSL) (n=28) and their counter‐part control flinders resistant line (FRL) rats (n=32) were subjected to forced swim (FST) and subsequently euthanized to collect plasma and both left‐ and right‐side hemispheres, including cerebellum. Along with higher immobility of the FSL rat, we found increased levels of the potential neurotoxin, 3‐hydroxykynurenine (3HK), and lower levels of both anthranilic acid (AA) and 5‐hydroxytryptophan (5HTP) in the brain as compared to the FRL rat (p<0.001). In plasma, 5‐
hydroxyindoleacetic acid (5HIAA) was higher in the FSL rats, where as picolinic acid, AA and quinolinic acid concentrations were lower as compared to the control FRL rats (p<0.0001). There were no hemisphere‐differences in TRYMETs. Thus, this study suggests that the interplay of both kynurenine and serotonergic pathway metabolites could be involved in the depressive‐like phenotype of FSL rats. 44 POSTER NR. 21 Modelling chronic inflammation in rats: behaviour and whole body adaptations Christina W Fischer, Betina Elfving, Sten Lund and Gregers Wegener Translational Neuropsychiatry Unit, AU Background Inflammation is the body’s first defence system against infections, but exaggerated inflammatory processes may be involved in chronic diseases, ranging from depression to diabetes. Chronic inflammation affects the whole body, from brain function and behavioural adaptations to energy regulation. Objective In order to understand the underlying mechanisms, the aim of this study was to develop a model of chronic inflammation in rats. Specifically, we assessed: 1) behavioural changes, 2) cytokine levels in the brain and in blood, and 3) peripheral adaptations. Methods Sprague‐Dawley rats (n=60) were randomized to receive a single (20h) or chronic (eight weeks) treatment with either lipopolysaccharide (LPS, 600μg/kg, i.p.) or saline. Behavioural tests included: locomotor activity in an open field, and depressive‐like behaviour in the forced swim test. 24 cytokines were investigated using a multiplexing technology (Luminex xMAP) and the Bio‐Plex® 200 platform (Bio‐Rad Laboratories, USA) in serum, frontal cortex, and hypothalamus. Results and discussion Interestingly, chronic LPS treated rats displayed similar sickness behaviour (decreased appetite, low activity level and depressive‐like behaviour) as acute LPS treated rats. However, distinct chronic inflammatory responses were detected; elevated pro‐inflammatory cytokines (IL‐1β and IFN‐γ) in the brain, induced local tissue responses (hepatomegaly and decreased fat mass), and hyperglycemia. Surprisingly, no cytokine changes were observed in serum following chronic LPS treatment, indicating compartment specific responses. Conclusion Taken together, chronic LPS administration induced multiple local inflammatory responses and behavioural adaptions. A model of chronic inflammatory sequelae could elucidate molecular mechanism behind psychiatric symptoms and therefore aid in targeting treatment options. 45 POSTER NR. 22 Comparing methods for genome‐wide gene‐environment interaction analysis Leslie Foldager1, 2, 3,4,#, Thomas Damm Als3,5, Jakob Grove2,3,4,5 1
Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Risskov, Denmark 2
Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark 3
iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus and Copenhagen, Denmark 4
iSEQ, Centre for Integrative Sequencing, Aarhus University, Denmark 5
Department of Biomedicine, Aarhus University, Aarhus, Denmark # Primary presenter Background Gene‐environment (GxE) interaction may be an important source of complexity in the etiology of psychiatric disorders but only few interactions have been reported, possibly due to the need of large samples in concert with environmental exposure information. The Danish iPSYCH study does, however, include such information. The number of methods and software available for GxE analysis is overwhelming and none appears superior. We present some initial results from a simulation study comparing a traditional two‐step approach and two machine learning methods. Methods Case‐control samples with individual‐based genetic data were simulated by use of simuPOP scripts allowing to model penetrances under restrictions specified by biological and epidemiological parameters and with interactions between two disease predisposing genetic markers and one predisposing environmental factor. The methods investigated are traditional two‐step logistic regression, logic feature selection regression (logicFS) and model‐based multifactor dimensionality reduction (MB‐MDR). Results Repeatedly generating one offspring from a base population by random mating and imposing affection status under certain scenarios, case‐control samples were drawn by rejection sampling. For each scenario, we generated 100 samples of 5,000 affected and 5,000 unaffected individuals and analysed for interactions by the different methods. Discussion When applying machine learning methods in practice several different methods, algorithms and/or sets of parameters are often used. If logicFS is to be used on a larger scale it will probably need to be reprogrammed to facilitate a parallelised search. The MB‐MDR software is more promising with respect to scalability and still developed with new algorithms that are more efficient. Funding: This study was funded by the Lundbeck Foundation, Denmark. Disclaimer: The Lundbeck Foundation had no involvement in any aspect of the study. Disclosure: None of the authors has conflicts of interest to disclose. 46 POSTER NR. 23 Conceptualization of Parental Self‐perceptions in the Autism Spectrum Disorder Literature: A Systematic Mixed Method Review Kirsten K. Frantzen Forskningsafsnittet, Børne‐ og Ungdomspsykiatrisk Center, Risskov Parental influence in child development in children with autism spectrum disorder is increasingly recognized as important. As there has been little previous research, a thorough examination of factors potentially influencing parental treatment preferences is needed. The primary aim of this review is to conceptualize the psychological construct of competence, control and self‐efficacy and potentially identify and review additional constructs. A secondary aim is to identify and review suitable parental self‐report measures for each of the psychological constructs of importance. A better conceptualization of these pivotal constructs would clarify their complex associations. The review illustrates that self‐efficacy and self‐esteem can be merged into competence, and the emergence of the coherence construct. Together, these constructs, competence, control and coherence can illuminate treatment preferences of parents of children with autism. The convergence of the constructs and the influencing factors suggest a superordinate concept of parental self‐
perception can more efficiently address relevant parental beliefs. 47 POSTER NR. 24 Psychiatric Disorder In Childhood and the Risk of Later Major Depressive Disorder L.K. Gundel1,2, C.B. Pedersen1,2,3, T. Munk‐Olsen1,2, S. Dalsgaard1,2,4 1 National Centre for Register‐based Research, School of Business and Social Sciences, Aarhus University 2 The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH 3
Centre for Integrated Register‐based Research at Aarhus University, CIRRAU 4 Department for Child and Adolescent Psychiatry, Hospital of Telemark, Kragerø, Norway Background Previous studies suggest an association between psychiatric disorders in childhood and the later development of major depressive disorders (MDD). However, no prospective population‐based cohort study has been able to directly compare the risks of MDD following a wide spectrum of child and adolescent psychiatric disorders. Aims To investigate the extent to which transitions from child and adolescent psychiatric disorders to MDD occur. A large, register‐based study was performed to estimate and compare the risk of later MDD in children diagnosed with one of ten psychiatric disorders. Methods Using Danish population‐based registers we identified persons born in Denmark from 1990 through 2000, and followed them from their 5th birthday through 2012. We calculated the incidence rate ratios of later MDD (ICD‐10: F32‐33) in children exposed to one of ten different psychiatric disorders. Estimates were calculated according to time between initial child and adolescent psychiatric diagnosis and diagnosis of MDD. Results We followed 960,026 persons, contributing 8,778,331 person‐years. Among these, 7,787 were diagnosed with MDD (incidence=1.7/1000 pyrs). Preliminary results suggest an increased risk of MDD five years after the first psychiatric diagnosis in eight of ten childhood disorders. Thus, children with a psychiatric disorder had a 1.75‐ to 3‐fold higher risk of an MDD five years or more after the initial diagnosis. Conclusions Most disorders were significantly associated with an increased risk of later MDD. Clinicians should be aware of emerging depressive symptoms in certain groups of patients and research should focus on common pathways between depression and other psychiatric disorders. 48 POSTER NR. 25 Vocalizations during tickling as a measure of depressive‐like behavior in a genetic rodent model of depression Linda Marie Kai Translational Neuropsychiatry Unit, Aarhus University, Risskov Rats emit high‐frequency sounds (USVs) inaudible to humans. When tickled the sound production increases ‐ assumed to reflect positive emotions. Preclinical researchers use the forced swim test to evaluate the effect of known and putative antidepressants on rat behaviour. But the test is stressful and may change the affectivity of the rats. The current study explores whether USVs offer an alternative none‐stressful, none‐harmful way of evaluating depressive‐like behaviour in rats. In this study we investigated the USVs of the Flinders Sensitive Line rats, a rodent model of depression, during six weeks of tickling. Flinders Resistant Line (FRL) rats, Sprague Dawley (SD) rats and a light‐touch group were used as controls. Due to the FSL rat’s depressive‐like phenotype we hypothesized a difference in emotional quality from the FRL and SD rats thus resulting in different USV profiles. The aims were to investigate: Firstly, whether USV profiles differ between the three rat strains; secondly, whether tickling has an antidepressant effect and thirdly, the effect of ketamine, a presumed rapid‐acting antidepressant, on the USV profile. Preliminary results reveal a marked, statistically significant, difference between strains in USV production upon tickling. The study is expected to help elucidate differences in the development of USVs following tickling stimulation between the FSL, FRL and SD groups, and furthermore to shed light on the effect of tickling on the behavioral phenotype. 49 POSTER NR. 26 Feasibility of group‐based Acceptance and Commitment Therapy for severe functional somatic syndromes in adolescents – a pilot study Kallesøe KH1, Preuss T1, Schröder A1, Fink P1, Rask CU 1,2 1 The Research Clinic for Functional Disorders and Psychosomatics, Aarhus University Hospital, DK 2
Child and Adolescent Psychiatric Center, Aarhus University Hospital, DK. Introduction Approximately 5‐10% of adolescents report recurrent functional somatic symptoms, i.e. symptoms not attributable to any known conventionally defined physical disease. Some experience persistent symptoms and may receive functional somatic syndromes (FSS) diagnoses, characterised by severe disability and reduced quality of life. Whereas FSS in adults have been shown to be managed effectively be means of psychological treatment, the evidence for adolescents is sparse. The aim of this pilot study was to evaluate the feasibility of group‐based Acceptance and Commitment Therapy (ACT) for severe FSS in adolescents. Methods Six young patients attended a manualised group‐based ACT‐ programme, specifically developed for adolescents (aged 15‐19 years) with severe FSS. The programme consisted of eight weekly 3 hours group sessions, and a booster session after one month. The Patient Satisfactory Form and a modified version of the Experience of Service Questionnaire (ESQ)) were completed after the last session to evaluate the patient’s opinions of the treatment. Results All participants rated the treatment as good to excellent; that they would recommend the treatment to a friend with similar problems and planned to use what they had learned in the future including various mindfulness exercises. The poorest scoring aspects were regarding completion of assigned homework and the need for more hand‐out material during the sessions. Conclusion The ACT‐based programme was well received by these young patients. A randomised controlled trial is planned to evaluate the treatment effects by the use of self‐reported outcome measures as well as by objective markers such as physiological stress response. 50 POSTER NR. 27 Endocannabinoid signaling in a genetic rat model of depression Christian Kirkedal Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University The aim of the study is to investigate how endocannabinoid (eCB) signaling in medial prefrontal cortex (mPFC) affects depression like‐behavior and glutaminergic neurotransmission in a verified animal model of depression namely Flinders Sensitive Line rats. Based on earlier preclinical stress model studies we propose that a decreased eCB signaling in mPFC may be involved in the depression‐like behavior of the rat model of depression. We will investigate the hypothesis in following three work packages: 1) How local enhancement of eCB signaling in mPFC of Flinders Sensitive Line rats alters their depression‐like behavior compared to ‘healthy’ controls and an imipramine treated FSL group. 2) Differences in expression of central eCB components in mPFC of Flinder Sensitive Line rats compared to controls. 3) How local enhancement of eCB signaling affects extracellular glutamate levels in mPFC of Flinders Sensitive Line rats compared to control. 51 POSTER NR. 28 The Diagnostic Stability of Psychiatric Patients with Borderline Personality Disorder. A Nationwide Study from 1995 through 2012 Jesper Nørgaard Kjær1, Robert Biskin2, Lea Nørgreen Gustasson1, Povl Munk‐Jørgensen1 1
Aarhus University Hospital, Department of Organic Psychiatric Disorders and Emergency Ward (Dep. M), Denmark 2
McGill University, Department of Psychiatry, Canada Introduction Borderline personality disorder (BPD) is a complex mental disorder of instability in affect regulation, impulse control, interpersonal relationships and self‐image. Comorbidity is common both within other personality disorders and other psychiatric disorders. Objectives The Danish Psychiatric Central Research Register (DPCRR) is nationwide and makes it possible to follow psychiatric patients over long periods. Thus the DPCRR can bring in new understandings of the diagnostic stability in BPD patients. Aims To determine the diagnostic stability of Danish psychiatric patients diagnosed with BPD from 1995 through 2012, and analyse the diagnostic profile before and after the first diagnosis of BPD. Methods All first time‐ever diagnoses of BPD among psychiatric inpatients were identified in the DPCRR from 1995 through 2012. Information of their previous and future admissions were grouped in accordance with ICD‐10. Results A total of 11,450 persons diagnosed with BPD were identified in the DPCRR between 1995 and 2012, 87.1 % were female. 37.0 % of men and 31.9 % of women had BPD as their first‐ever diagnosis. 41.4 % of men and 52.5 % of women had BPD as their latest registered diagnosis. Further we found that 85.5 % have had one or more main diagnoses additional to the BPD diagnosis. Most notable are stress‐related disorders, depressive disorders and psychotic disorders. Discussion/Conclusions We have shown that only about half of them who get BPD as their first‐ever diagnosis will also get it as their last. This can be due to both comorbidity or misdiagnosis. The same goes for the high percentage of patients with multiple psychiatric diagnoses. 52 POSTER NR. 29 Mental health patients´ experiences of patient education on psychiatric wards: a systematic review S.T. Kristiansen1, M. Kragh2,, P. Videbech3, M.B. Bjerrum4 1
Department of Public Health, Section for Nursing, Aarhus University, Denmark Aarhus University Hospital, Risskov, Centre for Psychiatric Research, Skovagervej 2, 8240 Risskov, Denmark 3
Department of Affective Disorders Q, Aarhus University Hospital, Risskov 4
Department of Public Health, Section for Nursing, Aarhus University, Denmark 2
Introduction Patient education may enhance patients´ capacity to cope with their illness and has shown to improve symptoms, increase adherence to treatment plans and support treatment choices. Patient education is associated with better compliance, improvements in quality of life and social functioning. WHO suggests, that suicidal behavior among mental health patients might decrease by improving patient centered information that responds to mental health patients direct educational needs. Aim To synthesize the best available evidence on how mental health patients´ experience patient education on psychiatric inpatient wards. Research questions What is the patient experienced effectiveness of patient education on psychiatric inpatient wards? How does patient education interventions meet mental health patients´ needs of information on psychiatric inpatient wards? Materials and methods This review considers male and female inpatients aged 18 and older suffering from: F20‐F29 and F30‐F39 (ICD‐10). Studies including patients with dual diagnosis of F20‐F29 and F30‐F39 plus substance abuse will also be of interest. The design is a systematic review that includes both quantitative and qualitative studies. The framework through which we conduct the systematic review is segregated methodology. By using this methodology we maintain a clear distinction between our quantitative and qualitative evidence and make individual syntheses prior to the final united synthesis. Perspectives The perspective of this systematic review is to aggregate knowledge, which can play an important role in explaining and discussing the usability, meaningfulness, feasibility and appropriateness of patient education in inpatient settings seen from the perspective of mental health patients. 53 POSTER NR. 30 Prevention of premature death of somatic causes in patients with mental illness and comorbid substance use disorder Anette Juel Kynde Department of Organic Disorders and Emergency Ward, M, Aarhus University Hospital, Risskov
Physical comorbidities are common in patients with mental illness and substance use disorder. Both regular use of alcohol and cannabis have been associated with adverse health effects. However, their physical comorbidities can also be explained by other unhealthy lifestyle choices, i.e. lack of physical activity, poor nutrition and smoking. The aim of this preliminary study is to analyse baseline data of a 3‐year interventional programme of improvement of physical health in patients with mentall illness and comorbid substance use disorder. All patients with mental illness and comorbid substance use disorder referred to department M at University Hospital, Risskov, Denmark from 1 july and onwards are included in the programme. We use an active awareness and motivational interviewing approach to increase knowledge and understanding of physical health problems. The intervention includes health promotion activities, and the physical health parameters are intensively monitored. Further guidance on healthy food intake, smoking cessation and a physically active life is given. In total, 39 patients have been included in the programme after 1 year (8 have dropped out). Patients have an insufficient food intake due to cannabis misuse. Further a majority of patients smoke cigarettes and their level of physical activity is low. In conclusion, this preliminary study indicates that patients with mental illness and comorbid substance use disorder need guidance on a healthier lifestyle. They show an interest in this interventional programme. 54 POSTER NR. 31 The private and social costs of ADHD in adults Daley, D.1,2, Jacobsen, R.3, Lange, A.M.4, Walldorf, J.3, Sorensen, A.3 1
Division of Psychiatry & Applied Psychology, School of Medicine, University of Nottingham, UK Centre for ADHD and Neurodevelopmental Disorders across the Life Span CANDAL Institute of Mental Health, University of Nottingham, UK 3
Department of Economics, Copenhagen Business School, Copenhagen, Denmark 4
Centre for Child and Adolescent Psychiatry Risskov, Aarhus University Hospital, Denmark 2
Introduction and objectives The full economic impact of Attention Deficit Hyperactivity Disorder on both the individual and society has yet to be determined. Previous explorations of the economic costs of ADHD have been restricted by an over reliance on analysis of insurance databases which leads to skewed sampling, and restricted outcomes mostly related to health care utilisation only (Doshi et al., 2011). Using the Danish National Registers this study aimed to explore the private and social costs of ADHD in adulthood and compare them against a carefully selected and matched control group. Methods From the Danish National Registers a group of 1431 individuals diagnosed with ADHD in adulthood and who had no other co‐morbid psychiatric disorder were identified. This group was compared against a gender matched sibling control group selected from the siblings of individuals in the treatment group also without psychiatric comorbidity. Results Compared with their non‐ADHD siblings the ADHD group demonstrated a significantly greater impact of their ADHD on personal costs (occupational status, personal income & educational attainment) and Social costs (receipt of state benefits, criminal offence, traffic accidents, foster care costs, and health‐care utilisation). Discussion The results demonstrate the considerable impact of unidentified ADHD in adults on both the costs incurred by individuals with ADHD and the state and underlines the potential savings that could come from earlier identification and access to care for individuals with ADHD. 55 POSTER NR. 32 The private and social costs of early versus late access to care for individuals with ADHD Daley, D.1,2, Jacobsen, R.3, Lange, A.M.4, Walldorf, J.3, Sorensen, A.3 1
Division of Psychiatry & Applied Psychology, School of Medicine, University of Nottingham, UK Centre for ADHD and Neurodevelopmental Disorders across the Life Span CANDAL Institute of Mental Health, University of Nottingham, UK 3
Department of Economics, Copenhagen Business School, Copenhagen, Denmark 4
Centre for Child and Adolescent Psychiatry Risskov, Aarhus University Hospital, Denmark 2
Background Early access to care (screening, diagnosis and treatment) is often claimed to be the most cost effective method of managing and treating psychiatric disorders (Gulliford et al., 2001) However, few studies have systematically evaluated the economic costs of earlier versus later access to care for individuals with ADHD. Method From the Danish National Registers two key groups were identified, i) a group of 4452 adults who received a registered diagnosis of ADHD in adulthood in the secondary health care sector in Demark but had not received a diagnosis in childhood. DIAGNOSED ADULTS DA. They were compared against a group of 3558 similar individuals who received an ADHD diagnosis in childhood, Controlling for demographics and co‐morbidity Diagnosed Child DC. Results DA individuals exhibited greater private and social costs compared to DC individuals. Specifically DA individuals were significantly less likely to be employed, to complete high school and paid less income tax, and were more likely to be in receipt of state benefits. Committed more crimes, and utilised more primary healthcare. Discussion The results demonstrate the additional economic burden associated with later identification of ADHD and suggest that earlier identification and intervention may lead to reduced costs for both the individual and the state. 56 POSTER NR. 33 Is nitric oxide involved in the antidepressant action of ketamine? Liebenberg N, Mikkelsen PF, Wegener G Translational Neuropsychiatry Unit, AU Background Stress‐induced excessive glutamate transmission at N‐methyl‐D‐aspartate receptors (NMDA‐R’s) may underlie a primary mechanism in the physiology that leads to depression, and ketamine, an NMDA‐R antagonist, has been shown to rapidly relieve depression in humans. A number of downstream mechanisms have been suggested to mediate the antidepressant action of ketamine, e.g. extracellular‐signal‐regulated kinases 1/2 (ERK1/2), protein kinase B (or Akt) and the mammalian target of rapamycin (mTOR). However, the mechanism(s) that are affected immediately downstream of NMDA‐R’s remain unclear. Methods We investigated whether the antidepressant mechanism of ketamine involves the inhibition of nitric oxide (NO) signalling. We used a genetic rat model of depression, the Flinders Sensitive Line (FSL) rats, and their control, the Flinders Resistant Line (FRL) rats, to investigate whether l‐arginine, a precursor of NO, can attenuate the behavioural antidepressant‐like effect of ketamine in FSL rats in the forced swim test (FST). We also measured the activity of nNOS, as well as the levels of cGMP and synaptophysin in the frontal cortex following the respective treatments. Four groups of FSL rats received vehicle (saline, i.p.), ketamine (15 mg/kg, i.p.), l‐arginine (250 mg/kg, i.p.) or a combination of ketamine and l‐arginine, and assessed in the FST 1 hour later, whereafter their brains were dissected for subsequent molecular assays. One vehicle‐treated group of FRL rats was used for validation. Results L‐arginine significantly attenuated the antidepressant‐like action of ketamine in the FST, indicating that ketamine may exert its antidepressant action by reducing NO signalling. Ketamine induced an increase in cGMP levels in both the frontal cortex and hippocampus, which was prevented by L‐arginine. Ketamine increased hippocampal NOS activity. Conclusions The bevioural results indicate that nNOS may indeed be involved in the antidepressant action of ketamine. In addition it appears that increased cGMP levels in the brain may be involved in ketamine’s antidepressant action, since increased cGMP correlated with depression‐like behaviour. 57 POSTER NR. 34 Mortality and secular trend in incidence of bipolar disorder Clara Reece Medici Forskningsenheden M0 / Forskerakademiet ved Povl Munk‐Jørgensen, AUH Risskov
The aims were to investigate secular trend in incidence of bipolar disorder in psychiatric care, examine the time lapse from first affective diagnosis to diagnosis of bipolar disorder and determine mortality and causes of death. All first‐ever diagnoses of bipolar disorder (ICD‐10 code F31) were identified in the nationwide Danish Psychiatric Central Research Register between 1995 and 2012. Patients were followed up until death or 31st of December 2012. Causes of death were obtained from The Danish Register of Causes of Death. We identified 15,334 incident cases of bipolar disorder. The total incidence rate increased from 18.5/100,000 person‐
years (PY) in 1995 to 28.4/100,000 PY in 2012. It was significantly higher in females. The age group with the highest incidence decreased from 60‐79 years to 20‐39 years. The mean time from first affective diagnosis to diagnosis of bipolar disorder was 7.9 years (SD=9.1). The standardized mortality ratio was 1.7 (95%‐CI=1.2‐2‐1). Causes of death were mainly natural, but 9% died from suicide. The incidence of bipolar disorder increased the past 10 years with excess death compared to the general population. Half of the patients were known with another affective disorder. Treatment to lower mortality in newly‐diagnosed patients needs focus on both natural and unnatural causes. 58 POSTER NR. 35 Metabolic profiles of 429 patients with schizophrenia and increased waist circumference: Baseline data from the CHANGE Trial Hans Christian Brix Nørgaard Forskningsenheden afd. P, Aarhus Universitetshospital Risskov Background People suffering from schizophrenia have a reduced life expectancy, with cardiovascular disease being the major cause of the increased mortality. Antipsychotic treatment, unhealthy lifestyle and insufficient monitoring and treatment of somatic co‐morbidity, including risk factors of cardiovascular disease (CVD), have been proposed as potential explanations. Objective To describe the proportion of subjects with risk factors above or below clinical recommendations. Method Baseline data for 429 patients with schizophrenia and increased waist circumference (WC). For women >88 cm for men >102 cm. Smoking was assessed self reported. We measured lipid profiles, HbA1c and blood pressure. Laboratory tests were non‐fasting. Blood pressure was measured 3 times after 5 minutes of rest. Results Mean age 38 (SD 12.4). 54% females. WC were 114cm (SD 16.6). 50% were daily smokers. Total cholesterol: 50% >5 LDL: 53% > 3.0, HDL: 56% <1.2. From the cohort 13.5% was diagnosed with type 2 diabetes and 0.5% with type 1. 9.7% had HbA1c >7.3 14% had systolic blood pressure>140 mm hg. 17.4 % was treated with a cholesterol lowering drug. 9.14% was treated with an antihypertensive drug. Conclusion The alarmingly high proportion of subjects suffering from metabolic disturbances call for immediate action regarding primary and secondary prevention of CVD in people with schizophrenia. It is important with an increased attention on the somatic co morbidities in this group of vulnerable patients. Further research should investigate if primary care can be better integrated in the care of this population. 59 POSTER NR. 36 How personalized medical data could improve health care. Okkels, N., Grinberg, A., Andersson, N.A.W. Afdeling M, AUH Risskov We present a redesign of medical test results by placing the information of blood samples in the context of the patient's personal clinical data (se figur). We predict that implementing personalized data in the treatment of patients will promote engagement in the treatment, motivate patients to take responsibility and lead to greater satisfaction with the patient‐doctor relationship. 60 POSTER NR. 37 PsychSim ‐ Virtual case encounters in psychiatric teaching Kamilla Pedersen SkejSim ‐ Medicinsk Simulation og Færdighedstræning og Forskningsenhed P, AUH, Risskov Forskningsprojektet PsychSim er baseret på et veletableret forskningsfelt kaldet ’medicinsk simulation’. Denne undervisningsform skaber en virkelighedsnær situation, der udgør en mere effektiv metode for fagprofessionelle og studerende til at opnå viden og træne færdigheder i et sikkert læringsmiljø uafhængig af tid og rum og uden risiko for at skade patienterne. Formålet med forskningsprojektet er at optimere læringsoplevelse og ‐udbytte i psykiatriundervisningen hos sundhedsfaglige professionelle ved brug af virtuelle cases i plenumundervisning og som et e‐læringsformat. De virtuelle cases er videofilmede sekvenser, som repræsenterer kliniske psykiatriske problemstillinger illustreret af skuespillere som simulerer patienter henholdsvis sundhedspersonale. Disse virtuelle cases designes, udvikles og testes ved 3 studier rettet mod: 1. Medicinstuderende på psykiatrimodulet til uddannelse som FADL‐vagt (videocases vist i plenum) 2. Medicinstuderende på 10. semester som forberedelse til 4 ugers psykiatripraktik (e‐læring) 3. Læger og psykologer under uddannelse i psykiatri på træningkursus i computer‐assisteret diagnostisk interviewteknik. (e‐læring). Ph.d. projektet vil udvide forståelsen af virtuelle, simulerede cases og deres bidrag til læringsprocessen i psykiatriundervisning med særlig fokus på holdninger til psykiatri samt træning af kommunikative og diagnostiske færdigheder. Projektet vil gennem den interaktive læring kunne reducere risikoen for utilsigtede hændelser og forbedre kompetencer i psykopatologi og differentialdiagnostik samt vurdering af og kommunikation med patienter, herunder triagering. Desuden kan projektet stimulere til øget interesse og hermed rekruttering til psykiatrifaget. 61 POSTER NR. 38 The flexibility of the absolutely conserved Leu99 is pivotal for overcoming the rate‐limiting conformational transition of the human serotonin transporter in serotonin transport Saida Said, Henriette Bjerregaard, Kasper Severinsen, Lina Malinauskaite, Caglanur Sahin, Poul Nissen, Steffen Sinning Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University The crystal structures of the bacterial leucine transporter (LeuT), which is a homolog to mammalian neurotransmitter sodium symporters (NSSs), have improved our understanding of ion selectivity, substrate binding as well as the transport mechanism of serotonin transporter (SERT) and other monoamine transporters. The substrate binding and translocation mechanism of serotonin by SERT has been an intense area of research. Approaches such as molecular dynamic (MD) simulations, substituted cysteine accessibility method (SCAM) and site‐
directed mutagenesis have been powerful complementary tools in the investigation of substrate/ion binding and transport mechanism in hSERT. Two recently determined crystal structures of LeuT in an outward‐oriented, substrate‐free, sodium‐free and presumed proton occluded state captures the structure of LeuT just after having returned to an outward‐facing conformation from an inward‐facing conformation, but before the binding of ions or substrate, contrary to existing structures. These new structures can reveal how the transporter is able to achieve this conformational transition and overcome what is believed to be the rate‐determining step in the conformational cycle. The new structures reveal an unexpected 180 degree flip of a highly conserved Leu25 that facilitates the conformational transition of the transporter in a substrate‐free state. To test the role of the conserved residue in substrate/ion binding as well as in the transport mechanism, the corresponding Leu99 in the hSERT was mutated to seven different residues. Our results from uptake experiments show preserved substrate apparent affinity (KM) in all seven mutants. However, the maximum transport rates (VMax) were significantly lower than hSERT wt, indicating that Leu99 is not directly involved in the substrate binding, but plays a crucial role in conformational transitions necessary for completion of the transport‐associated conformational cycle. The conformational changes that these hSERT mutants can adopt in response to binding of cations and substrate were assessed by means of SCAM experiments. Our results show that this Leu99 plays a pivotal role in the conformational changes necessary for serotonin transport. Combined, the remarkable flip of the Leu25 in the crystal structures and how impairing this flip by mutating this residue impacts on transport kinetics and transporter conformational change provides an elegant mechanistic solution to overcoming the rate‐limiting step in the transport‐associated conformational cycle. Furthermore, it explains the functional background leading to an evolutionary pressure that has forced conservation of this residue in nearly all NSS family members from bacteria to mammals. 62 POSTER NR. 39 Deep brain stimulation in treatment‐resistant depression: exploratory meta‐analysis Donald F. Smith Institute for Clinical Medicine, Translational Neuropsychiatry Unit, Psychiatric Hospital of Aarhus University, 8240 Risskov, DK Background Deep brain stimulation is currently an experimental treatment for major depressive disorder. Information is lacking, however, on how sham responding may affect efficacy. This project applied exploratory meta‐analysis to address that topic. Methods Data on benefits of deep brain electrical stimulation come from a recent review. Stimulated brain regions included subgenual cingulate, capsular interna, nucleus accumbens, and medial forebrain bundle. Expert opinion plus random number software was used to generate hypothetical values for sham responding. Results An effect size of 1.71 (95% C.I.: 1.47 – 1.96) was obtained for deep brain stimulation versus sham treatment in patients suffering from long‐term treatment‐resistant depression. Conclusion Deep brain electrical stimulation may be 71% more effective than sham for alleviating symptoms of depresssion in subjects suffering from long‐term treatment‐resistant depression. Expressing these findings as patients‐needed‐to‐treat, deep brain electrical stimulation is required by 2.9 treatment‐resistant patients in order for one of them to benefit 63 POSTER NR. 40 ”Fælleslæsning” som Mental Sundhed. Mette Steenberg og Nicolai Ladegaard Afdeling Q, AUH Risskov Fælleslæsning er en æstetisk praksis, baseret på højtlæsning af litterære tekster og fælles refleksion. Denne praksisform har gennem de sidste 10 år fundet indpas i det engelske sundhedssystem indenfor feltet ”participatory arts practices”, der fokuserer på effekten af det deltagende engagement for den enkeltes mentale sundhed. Fælleslæsning har vist sig særdeles velegnet som æstetisk praksis i psykiatrien, fordi formen (højtlæsning af korte prosatekster) tager hensyn til det reducerede kognitive funktionsniveau, der ofte observeres i forbindelse med både affektive lidelser og psykoser, samtidig med at aktiviteten træner netop koncentration, opmærksomhed og hukommelse. Vores hensigt med ”fælleslæsning” er derfor at udvikle en interventionsform, der både giver den enkelte patient en øget oplevelse af personligt velvære, herunder styrker relationer, og fungerer som en form for kognitiv remediering. 64 POSTER NR. 41 Attitudes towards pertinent and incidental findings and consenting procedures in whole genome sequencing studies in psychiatric research Anna Sundby Institut for Klinisk Medicin, Aarhus Universitet, Instituttet for Biologisk Psykiatri, PC. Sct. Hans, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, IPSYCH Background In 2007 the first individual genome was sequenced for research purposes and whole genome sequencing (WGS) is rapidly emerging as an important tool in human genetics research. WGS has made it possible to identify genetic variations for many disorders but makes it possible also to identify genetic variation unrelated to the primary focus of the research. Aim This study explores ethical implications of WGS and focuses on the attitudes of potential research subjects towards pertinent findings (PF) and incidental findings (IF) and consenting procedures. Methods We made a pilot study including 6 interviews with genetic researchers, 3 interviews with patients with schizophrenia and 4 focus group interviews with clinical geneticists, relatives of psychiatric patients, patients with ADHD and blood donors. Preliminary results of pilot study Most of the genetic researcher’s support a broad consent but the clinical geneticists and patients are concerned whether a broad consent would be an informed consent. Nearly all participants believe that pre‐ and post‐test counselling is necessary. The majority of the research subjects express strong preferences regarding how and if they should be informed about PF and IF. Next step We have translated and modified a web‐based questionnaire designed by the Wellcome Trust Sanger Institute to examine the attitudes to WGS research in a Danish context. The questionnaire uses films as a medium to illustrate the ethical dilemmas. Potential research subjects were invited to complete the questionnaire in August 2014. Conclusion Our pilot study indicates that attitudes toward feedback of findings vary across different groups of participants. There are both arguments for and against a broad consent. This study indicates that we need to discuss: How to handle the findings in a way that respects the attitudes of different groups? Whether a broad consent is sufficient to deal with the feedback of IF? 65 POSTER NR. 42 Mapping Neuronal Substrates of Stress Susceptibility and Resilience in the Chronic Mild Stress Model of Depression Katrine Svenningsen, Fabia Febbraro and Ove Wiborg Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Skovagervej 2, DK‐8240 Risskov, Denmark Stress and stressful life events have repeatedly been shown as causally related to depression. The Chronic Mild Stress (CMS) rat model is a valid model of stress‐induced depression. Like humans, rats display great heterogeneity in their response to stress and adversity. Basal differences in the brain architecture and function may account for why some individuals are more vulnerable to stress than others. The aim of the present study was to identify neuronal substrates associated with stress‐resiliency and stress‐susceptible CMS endophenotypes. Stress‐induced modulation of neuronal activation patterns in response to the CMS regime was mapped according to the expression of the immediate early gene, c‐Fos, as a marker. Quantification of the Fos‐like immunoreactivity (FLI) responses was performed by design‐based stereology and densitometric analysis. The VLGMC substructure was found to be susceptible to CMS exposure. This was an effect of stress per se and not specifically associated to depression‐like behavior. Additional six out of the thirteen investigated areas were also found to be responsive to CMS. Contrary to the VLGMC, the effects of CMS upon the FLI responses within these areas associated with the hedonic status of the rats. More specifically the ventral hippocampus, lateral habenula, and ventral orbital cortex were found only to be responsive in stress‐resilient rats, whereas the medial habenula, infralimbic cortex and lateral orbital cortex were found only to be responsive in stress‐susceptible rats. Therefore these areas might be associated to stress‐coping mechanisms underlying the CMS induced segregation into stress‐susceptible and stress‐
resilient endophenotypes. 66 POSTER NR. 43 Feasibility of using text messaging for continuous measurement of physical symptoms, mood, and worries in children and adolescents – a pilot study M. Thorgaard1, L. Frostholm1,T. Connor2, C. Rask1,3 1
The Research Clinic for Functional Disorders, Aarhus University Hospital, Denmark 2
Department of Psychology, University of Otago, New Zealand 3
Child and Adolescent Psychiatric Centre, Risskov, Aarhus University Hospital, Denmark Background Experience Sampling Method (ESM) – a structured diary technique – can be used to study daily fluctuations in thoughts, mood and symptoms in subjects in their normal living environment. Using ESM in terms of text messaging to study e.g. psychopathology in children seems feasible because this group is familiar with text messaging. This pilot study on the use of ESM is a part of a larger study on health anxiety in children. Objective To examine the potential of ESM (text messaging) for continuous measurement of children’s and adolescents’ physical symptoms, mood and worries on a daily basis. Methods In total 12 children aged 9‐17 were included in this pilot study. The children filled out standardized questionnaires about their physical symptoms, health anxiety, mood, and life quality. In the following week they received text messages 4 times a day send in a randomly sampled design. Preliminary results One child were excluded due to a very low response rate of the text messages (=15%). The remaining 11 children had a response rate of an average of 83% (range from 49%‐100%). Conclusion Overall the ESM (text messaging) seemed to be a feasible method to use in this age group. The preliminary data suggest a lower response rate among younger children compared to adolescents. Perspectives We expect that the main study can provide additional knowledge about the use and feasibility of ESM (text messaging) for continuous measurements of children´s and adolescents´ physical symptoms, worries and mood on a daily basis. 67 POSTER NR. 44 Effects of stress and glucocorticoid on glutamateric transmission in prefrontal and frontal Cortex Giulia Treccani Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University Hospital Several studies suggest a critical role of glutamatergic neurotransmission in the stress response. In this work we compared the effects of acute behavioural stress with the effects of in vitro application of corticosterone (CORT) to prefrontal/frontal cortex (PFC/FC) synaptosomes, to verify if stress effects on glutamate neurotransmission were mediated by a synaptic action of CORT. We found that both acute stress and CORT in vitro increase the size of the readily releasable pool (RRP) of vesicles in PFC/FC synaptosomes. This effect was abolished by selective mineralocorticoid or glucocorticoid receptor (MR/GR) antagonists. However, CORT did not affect glutamate release evoked by depolarization and did not alter excitatory transmission in medial PFC and did not alter excitatory transmission in medial PFC slices. We then confirmed, by using TIRFM, that CORT increases vesicle mobilization toward the RRP acting on synaptic GR/MR. Finally, we found that both stress and CORT increase the phosphorylation of synapsin I at site 1 in presynaptic membrane. This increase of synapsin I phosphorylation was also found to be dependent on GR/MR and necessary for the increase of RRP. Thus the rapid increase of RRP size whereby CORT primes synaptic terminals in PFC/FC, the synaptic non‐genomic action of CORT is necessary but not sufficient to enhance glutamate release. 68 POSTER NR. 45 Cholesterol affects the conformational equilibrium and substrate affinity of the serotonin transporter Kasper Severinsen, Louise Laursen, Kristina B. Kristensen, Pernille F. Martens, Mie Ulvbjerg, Steffen Sinning Translational Neuropsychiatry Unit, Department of Clinical Medicine, Health, Aarhus University. The serotonin transporter (SERT) is a membrane transport protein, which is localized in the pre‐synaptic membrane of serotonergic neurons, where it actively reuptakes the neurotransmitter serotonin from the synapse after its release in serotonergic signaling. The efficiency by which SERT depletes serotonin depends on a number of conformational changes during the transport cycle and its affinity for serotonin. Increasing evidence suggests that the lipid environment of the membrane is important for the functionality of many membrane proteins. In this study, we have focused on cholesterol and its role in modulating the transport dynamics of SERT. We have manipulated the cholesterol contents in membranes and determined the effects on ligand affinity. In addition we used the substituted cysteine accessibility method (SCAM) to determine the effect on the conformational equilibrium, and a combination of SCAM and mutagenesis to validate the presence of a cholesterol binding site in SERT inferred from a recent insect DAT structure. Together our data suggest a direct interaction between cholesterol and SERT and a clear role for cholesterol in the transport mechanism. 69 POSTER NR. 46 Health anxiety symptoms in children and adolescents assessed for OCD Anna Villadsen1,2, Mette Viller Thorgaard1, Katja Anna Hybel2, Per Hove Thomsen2, Charlotte Ulrikka Rask1,2 1
Forskningsklinikken for Funktionelle Lidelser, AUH Børne – og Ungdomspsykiatrisk Center Risskov, AUH 2
Objektivt Studiet vil være et af de første, også internationalt, der undersøger symptomer på helbredsangst hos børn og unge henvist til udredning for OCD. Helbredsangst er en lidelse, hvor man i overdreven grad bekymrer sig om at fejle noget alvorligt. Bekymringerne er vedvarende og almindelige kropslige symptomer tolkes ofte som tegn på alvorlig sygdom. Pga. manglende viden, fravær af specifikke diagnostiske kriterier og lighed med andre angstlidelser, herunder OCD, er der grund til at antage, at børn med mulig svær helbredsangst i stedet får andre diagnoser og dermed ikke den rette, specifikke behandling. Metode Der indsamles data på ca. 100 børn og unge i alderen 8‐17 år, som er henvist til udredning for OCD på Børne‐ og Ungdomspsykiatrisk Center, Risskov, AUH. Som led i udredningen udfylder barnet/den unge ”The Childhood Illness Attitude Scales (CIAS)”; et standardiseret spørgeskema omhandlende symptomer på helbredsangst. Information om barnets fysiske helbred og kontakter til den primære sundhedssektor via journalmateriale og registeroplysninger og det kliniske team udfylder: ”The Children’s Yale‐Brown Obsessive‐Compulsive Scale” (CY‐BOCS) til undersøgelse af OCD symptomer. I efterfølgende analyser ses på sammenhænge mellem symptomer på helbredsangst, forbrug af sundhedsydelser, somatiske helbredsproblemer og OCD symptomer. Resultater Resultaterne forventes at kunne bidrage til at afklare om udtalte sygdomsbekymringer hos børn og unge under udredning for OCD bedst kategoriseres og behandles som en undertype af OCD eller som helbredsangst. Det kan få betydning for det fremtidige udrednings‐ og behandlingsforløb for unge patienter med OCD og potentielt bidrage til at udvikle aldersspecifikke diagnostiske kriterier for helbredsangst. 70 POSTER NR. 47 Vågen‐ og lysterapi til indlagte patienter med depression Behandlingseffekt, prædiktorer og patientoplevelse Kragh Mette Kragh, Camilla Schultz Wihlborg, Dorthe Jensen, Klaus Martiny, Tove Lindhardt og Poul Videbech Afdeling Q – Afdeling for Angst og Depression, Aarhus Universitetshospital, Risskov Baggrund Patienter, der indlægges med depression, er svært forpinte, og mange har selvmordstanker. Behandlingen består af opstart eller justering af antidepressiv medicin kombineret med eksempelvis miljøterapi, samtaleterapi og motionstilbud. Fuld effekt af behandlingen opnås ofte først efter 4‐6 uger. Vågenterapi er en behandlingsmetode, der kan ophæve eller reducere depressive symptomer inden for timer, og i flere undersøgelser er det påvist, at op mod 60 % af patienterne responderede på vågenterapi. Metoden består i, at patienterne holder sig vågne en nat og den efterfølgende dag, i alt 36 timer, hvilket efterfølges af en nats søvn. Lysterapi, stabilisering af døgnrytmen, samt antidepressiva har vist sig at kunne fastholde den akutte effekt af vågenterapi. Formål At undersøge effekten af at anvende vågen‐ og lysterapi samt stabilisering af døgnrytmen som et supplement til vanlig behandling ved indlagte patienter med depression. Endvidere er formålet at identificere prædiktorer for god effekt samt belyse patienternes oplevelse af vågen‐ og lysterapi. Metode Projektet gennemføres som et randomiseret kontrolleret studie med 74 patienter, som allokeres til en kontrolgruppe, som vil modtage vanlig behandling (n=37), eller til en interventionsgruppe (n= 37). Interventionen vil ud over vanlig behandling bestå af tre gange vågenterapi i én uge med en nats søvn imellem. Patienterne får desuden i hele studieperiodens ni uger lysterapi i 30 minutter hver morgen samt løbende støtte, vejledning og undervisning i at opbygge eller fastholde en stabil døgnrytme. Patienterne opfordres til at føre dagbog, og ved studiets afslutning gennemføres individuelle semistrukturerede interviews for at belyse patienternes oplevelse af behandlingen. 71 POSTER NR. 48 Maternal perinatal high‐fat diet increases anxiety‐like behavior in male offspring Gudrun Winther Translational Neuropsychiatry Unit, Skovagervej 2, 8240 Risskov Background Maternal obesity during gestation represents a significant health risk for the offspring. This becomes evident later in life and includes metabolic syndrome, cardiovascular disease and affective disorders. Inflammation has recently been shown to play an important role in the pathophysiology of affective disorders. Systemic inflammation is a hallmark consequence of a high‐fat diet and maternal obesity may lead to fetal inflammatory responses. Therefore, we hypothesize that an altered immune response could be responsible for the metabolic and psychiatric symptoms in the offspring. Objective The objective of this study was to investigate the influence of a high‐fat diet on the affective‐like behavior in the offspring. Methods Female rats (n=20) were fed a high‐fat diet or a control diet 8 weeks before breeding, and continued on this diet throughout gestation and lactation. Male and female offspring were tested at the age of PND56 in different behavioral settings. Plasma cytokines were determined by Luminex liquid array‐based multiplexed immunoassays. Results After 8 weeks on the obesogenic diet, female rats had a significantly higher intake (Kcal) than control dams. Offspring from high fat fed rats were significantly heavier than control offspring at weaning. Male offspring exposed to perinatal high‐fat showed increased time spent in the closed arm in the elevated plus‐maze indicating anxiety‐like behavior. Conclusion The data strongly suggest that that dietary environment during development contributes to behavioral consequences. This effect seems to be specific for anxiety‐like behavior. 72 Tak til: Arrangørerne ønsker at takke Region Midtjylland for at stille økonomiske midler til rådighed, samt Karen Jul Madsen og Hella Kastbjerg for ekstraordinær indsats i forbindelse med forberedelserne til mødet og udarbejdelse af programmet. 73