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The World’s Best Bipolar Assessment
Lecture in the World
with a Treatise on the Scientific Proof of God as well as the Cure for Cancer
Jonny Gerkin, MD
Asst Professor, UNC Psychiatry
Bipolar I Disorder requires a history of
a manic episode.
• The easier, although not easy, question is: Is this
individual currently manic?
– http://www.youtube.com/watch?v=rdnAHvi2ynQ
• The tougher question arises in the context of a
patient that is not currently manic. Have they
ever been manic?
– http://www.youtube.com/watch?v=TiGRi0kGg_s&feat
ure=related
The future…
World Biol Psych. 2011 Sep 22.
• Identification of a blood-based biological signature in subjects with psychiatric disorders prior to
clinical manifestation.
• Schwarz et al. Department of Chemical Engineering and Biotechnology, University of Cambridge ,
Cambridge , UK.
Abstract
• Objectives: To determine whether a molecular signature is present in blood of patients with
psychiatric disorders before manifestation of symptoms.
• Methods: Multiplex immunoassay analyses were carried out using serum obtained from two casecontrol studies of schizophrenia (n = 75) and bipolar disorder (n = 110) patients and their matched
controls. The samples were drawn within 1 month before estimated onset of illness. Results. This
led to identification of 20 molecules which were altered in pre-schizophrenia and 14 molecules in
pre-bipolar disorder subjects compared to controls. Only two of these molecular changes were
identical in both data sets and predictive testing confirmed that the biomarker signatures for preschizophrenia and pre-bipolar disorder were dissimilar.
• Conclusion: The present results suggest that there are distinct serum alterations that occur before
clinical manifestation of schizophrenia and bipolar disorder. These findings could lead to
development of diagnostic tests to help clinical psychiatrists identify and classify vulnerable
patients early in the disease process, allowing for earlier and more effective therapeutic
intervention.
More of the future…for schizophrenia
Mol Psychiatry 2011 Apr 12.
• Identification of a biological signature for schizophrenia in serum.
• Schwarz et al. Institute of Biotechnology, University of Cambridge, Cambridge, UK.
Abstract
• Biomarkers are now used in many areas of medicine but are still lacking for psychiatric conditions
such as schizophrenia (SCZ). We have used a multiplex molecular profiling approach to measure
serum concentrations of 181 proteins and small molecules in 250 first and recent onset SCZ, 35
major depressive disorder (MDD), 32 euthymic bipolar disorder (BPD), 45 Asperger syndrome and
280 control subjects. Preliminary analysis resulted in identification of a signature comprised of 34
analytes in a cohort of closely matched SCZ (n=71) and control (n=59) subjects. Partial least squares
discriminant analysis using this signature gave a separation of 60-75% of SCZ subjects from controls
across five independent cohorts. The same analysis also gave a separation of ∼50% of MDD
patients and 10-20% of BPD and Asperger syndrome subjects from controls. These results
demonstrate for the first time that a biological signature for SCZ can be identified in blood serum.
This study lays the groundwork for development of a diagnostic test that can be used as an aid for
distinguishing SCZ subjects from healthy controls and from those affected by related psychiatric
illnesses with overlapping symptoms.
In the meantime…
• Clinical exam,
observation and
exclusion of
SECONDARY mania
• For our purposes we
will focus on the
interview and exam
Screening questions
• The most effective
screening questions for
mania ask about other
people’s perceptions as
well as the patient’s
self-perception.
Screening questions continued..
• Have you ever had a period
of a week or so when you
felt so happy and energetic
that your friends told you
that you were talking too
fast or that you were
behaving differently and
strangely?
Screening continued...
• Has there been a period
when you were so hyper
and irritable that you got
into arguments with
people?
More example screening questions..
• Has there been a time when you felt just the
opposite of depressed, so that for a week or so
you felt as if you were on an adrenaline high
and could conquer the world? (this might be a
segue from depression screening questions)
More examples..
• Do you experience wild mood swings in which
you feel incredibly good for a week or more
and then crash down into a depression?
– Interpret responses to this question cautiously,
because some patients who respond with an
emphatic “yes” are referring to recurrent episodes
of depression without mania or hypomania.
More examples…
• Has there been a time when you were so hyper and
irritable that you got into arguments with people?
– This gets at the diagnosis of irritable, mixed, or dysphoric
mania. Obviously, false-positive responses abound here,
and following up with questions establishing that this
period of irritability represented a manic episode, rather
than a depression or simply a transient foul mood, will be
no small task.
• Has anyone ever called you manic?
– If someone answers “yes” to this, pay close attention. It’s
not common for healthy people to have been called manic
by someone.
Screening continued…
• If you get yes to one or more of these, find out
how long it lasted and when that period was.
– If the patient cannot remember such a period
lasting an entire week, you should suspect that
mania is not the diagnosis.
– Determine the circumstances of the elevated
mood. Being really happy for a couple of days
after matching into your top choice derm
program, for example, is not mania.
How do we deal with the significant
potential for false positives?
• Like we said earlier:
– ask about other
people’s perceptions
too.
– determine the length of
such a period of time.
– explore the
circumstances
surrounding the change
in mood, any substance
use?
Also…
• Continually refer to that period (when they profess to have had
the expansive mood) when you ask about the diagnostic
criteria for mania.
DIGFAST apparently refers to the speed with which a
manic patient would dig a hole if put to the task.
•
In addition to expansive mood, the patient must qualify for three of the seven
DIGFAST symptoms, or four of seven if the primary mood is irritable.
DIGFAST (manic episode)
•
•
•
•
•
•
•
Distractible (poorly focused)
Indiscretion (excessive pleasurable activities)
Grandiosity (unrealistic belief in one’s abilities)
Flight of Ideas
Activities (increased goal direction)
Sleep deficit (decreased need for sleep)
Talkativeness (pressured speech)
DIGFAST cont’d
• When you ask about the symptoms of mania,
precede your questions with something such
as, “During the period last year when you felt
high, were you…?” This way, you can ensure
that all the symptoms have occurred within
the same time frame.
• See handout: DIGFAST Interviewing Tips
Other important aspects of
assessment
• History of hospitalization: If a patient was
hospitalized during a “hyper” period, chances are
good that this was indeed a manic episode.
• Interview with relatives and friends: One of the
hallmarks of mania is a lack of insight, making
verification of historical information particularly
important.
• Family history of bipolar disorder: Bipolar
disorder is one of the most inheritable of all
psychiatric disorder.
DDX:
•
•
•
Psychiatric
Mood Disorder Due to a General Medical Condition; Dementia with Mood
complications; Substance-Induced Mood Disorder; Other varieties of Mood or
Bipolar Disorders (II), +/- Rapid Cycling; Schizoaffective Disorder; Schizophrenia
(other primary psychotic illnesses); Borderline Personality Disorder (other ,
primarily Cluster B personality disorders); ADHD; PTSD; Anxiety Disorders (OCD)
Medical
Secondary Mood Syndromes caused by: Acquired Immune Deficiency Syndrome
(AIDS), Cushing's Disease, Epilepsy, Hyperthyroidism, Premenstrual Syndrome,
Migraines, Multiple Sclerosis, Neoplasm, Stroke, Systemic Lupus Erythematosus,
Traumatic Brain Injury, Delirium (e.g. Uremia), Vitamin Deficiency/Excess, Wilson's
Disease, Acute Intermittent Porphyria, Fahr's Syndrome, Huntington's Disease
Substances/Drugs
Amphetamines/Stimulants, Illicits, Antidepressants (treatment or withdrawal),
Dopaminergics (Bromocriptine), Gaba-ergics (Baclofen), Anticholinergics,
Corticosteroids (including ACTH), Chemotherapeutic agents (Cyclosporin), Opiates,
Supplments/CAM (Yohimbine, Ginseng)
Comorbitdity
• Generally comorbid to Mood D/O’s are etoh
abuse/dep, panic, OCD and social anxiety.
• Bipolar I folks 2X as likely to have above
comorbidities than MDD, BPII even higher
• Men: substance use disorders
• Women: anxiety, eating disorder
Some Epidemiology
• Data on lifetime prev
varies; but it indicates a
rate of around 0.5%–
2.4% for bipolar I (MDD
5-17%), 0.3-4.8% for
bipolar II, 0.5-6.3% for
cyclothymia, 2.6-7.8%
for hypomania.
• Gender ratio generally
1:1 for BP1 (MDD 2:1,
F:M)
Some genetics…
• For bipolar I, the concordance rates in modern studies have been
consistently put at around 40% in monozygotic twins, compared to
0 to 10% in dizygotic twins, these suggest genes explain only 5070% of etiology implying predisposition is inherited
• 3.5-8% risk with 1st degree relative
• Multifactorial-threshold model (complex/heterogeneous) with
variable expressivity (same gene or group of genes resulting in
variety of forms of illness), also imprinting (different traits result
from maternal/paternal transmission) may effect the penetrance
(probability that someone will manifest a given trait given that they
have a certain genotype)
• Assortative Mating – mood disordered folks are more likely to
marry other mood disordered folks
Predictive features
(especially in combination)
• Early age at onset, ave is 20 & ten
years less than MDD onset
• Psychotic depression before 25 yr
old
• PP depression, especially
w/psychotic fx
• Rapid onset/offset of depression
(<3mo)
• Depression w/marked
psychomotor fx
• Atypical fx (reverse vegatative
signs)
• Depressive mixed state
(psychomotor excitement,
irritable hostility, racing thoughts,
sexual arousal during MD)
• Seasonality
• Family History
• High-density 3 generation
pedigrees
• Trait mood lability (cyclothymia)
• Hyperthymic temperament
• Hypomania assoc’d with
antidepressants
• Repeated loss of efficacy of
antidepressants (at least 3 times)
Broader indicators
• Agitated depression
• Cyclical depression
• Episodic sleep
dysregulation
• Or combination of these
• Refractory depression (as
above)
• Depression in someone
with an extroverted
profession
• Periodic impulsivity
(gambling, sexual
misconduct, wanderlust)
• Periodic irritability and/or
periodic suicidal crises
• Depression with erratic
personality disorders
Psychodynamic view of Mania
• Playing the manic game: Interpersonal maneuvers of the acutely
manic patient.
– Janowsky, David S.; Leff, Melita; Epstein, Richard S. 1970.
• Describes the personality structure, patterns of interaction, and
impact on others of the manic-depressive patient in a study of 15
patients in the acute manic phase of their illness. Hypotheses are
presented concerning patient‘s conflicted needs for dependency
and intimacy, manifested in attempts to control and manipulate
others. It is stressed that firm limits and controls by the therapist
can often reduce manic symptomatology by convincing the patient
"that the therapist cares enough and is powerful enough to protect
him from his self-destructive activities."
What about Bipolar II and Hypomania?
• Hypomania can be hard and pretty unsatisfying to
diagnose. Essentially, it amounts to a psychiatric
diagnosis for exuberant and often very productive
happiness. However, patients with bipolar II spend
much of their non-hypomanic time in depression,
which is why bipolar II is important not to miss. Use
the same DIGFAST questions to diagnose hypomania
that are used to diagnose mania. The patient with
hypomania will describe definite high periods that have
not caused real problems in her life. When hypomanic
periods alternate with depressed periods, the proper
diagnosis is bipolar, type II disorder.
DSM IV Criteria of BP1
• The essential feature of Bipolar I Disorder is a clinical course that
is characterized by the occurrence of one or more Manic Episodes
or Mixed Episodes. Often individuals have also had one or more
Major Depressive Episodes. Episodes of Substance-Induced Mood
Disorder (due to the direct effects of a medication, or other
somatic treatments for depression, a drug of abuse, or toxin
exposure) or of Mood Disorder Due to a General Medical
Condition do not count toward a diagnosis of Bipolar I Disorder. In
addition, the episodes are not better accounted for by
Schizoaffective Disorder and are not superimposed on
Schizophrenia, Schizophreniform Disorder, Delusional Disorder, or
Psychotic Disorder Not Otherwise Specified. . . .
DSM IV Criteria for Mania
•
A. A distinct period of abnormally and persistently elevated, expansive, or irritable mood, lasting at least
1 week (or any duration if hospitalization is necessary).
•
B. During the period of mood disturbance, three (or more) of the following symptoms have persisted
(four if the mood is only irritable) and have been present to a significant degree:
–
–
–
–
–
–
–
inflated self-esteem or grandiosity
decreased need for sleep (e.g., feels rested after only 3 hours of sleep)
more talkative than usual or pressure to keep talking
flight of ideas or subjective experience that thoughts are racing
distractibility (i.e., attention too easily drawn to unimportant or irrelevant external stimuli)
increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation
excessive involvement in pleasurable activities that have a high potential for painful consequences (e.g.,
engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments)
•
C. The symptoms do not meet criteria for a Mixed Episode.
•
D. The mood disturbance is sufficiently severe to cause marked impairment in occupational functioning
or in usual social activities or relationships with others, or to necessitate hospitalization to prevent harm
to self or others, or there are psychotic features.
•
E. The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a
medication, or other treatments) or a general medical condition (e.g., hyperthyroidism).
Note: Manic-like episodes that are clearly caused by somatic antidepressant treatment (e.g., medication,
electroconvulsive therapy, light therapy) should not count toward a diagnosis of Bipolar I Disorder.
DSM IV Criteria for Mixed Episode
• A. The criteria are met both for a Manic Episode and for a Major
Depressive Episode (except for duration) nearly every day during
at least a 1-week period.
• B. The mood disturbance is sufficiently severe to cause marked
impairment in occupational functioning or in usual social activities
or relationships with others, or to necessitate hospitalization to
prevent harm to self or others, or there are psychotic features.
• C. The symptoms are not due to the direct physiological effects of
a substance (e.g., a drug of abuse, a medication, or other
treatment) or a general medical condition (e.g., hyperthyroidism).
DSM IV Criteria for MDE
(for completeness)
•
A. Five (or more) of the following symptoms have been present during the same 2-week period and represent a change from
previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure.
Note: Do not include symptoms that are clearly due to a general medical condition, or mood-incongruent delusions or
hallucinations.
– depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad or empty) or
observation made by others (e.g. appears tearful). Note: In children and adolescents, can be irritable mood.
– markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by
either subjective account or observation made by others)
– significant weight loss when not dieting or weight gain (e.g., a change of more than 5% of body weight in a month), or
decrease or increase in appetite nearly every day. Note: In children, consider failure to make expected weight gains.
– insomnia or hypersomnia nearly every day
– psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or
being slowed down)
– fatigue or loss of energy nearly every day
– feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely selfreproach or guilt about being sick)
– diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by
others)
– recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or
a specific plan for committing suicide
•
B. The symptoms do not meet criteria for a Mixed Episode.
•
C. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.
•
D. The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a general
medical condition (e.g., hypothyroidism).
•
E. The symptoms are not better accounted for by bereavement, i.e., after the loss of a loved one, the symptoms persist for longer
than 2 months or are characterized by marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation,
psychotic symptoms, or psychomotor retardation.
DSM IV Criteria for Hypomanic Episode
•
A. A distinct period of persistently elevated, expansive, or irritable mood, lasting throughout at least 4 days, that is clearly
different from the usual nondepressed mood.
•
B. During the period of mood disturbance, three (or more) of the following symptoms have persisted (four if the mood is
only irritable) and have been present to a significant degree:
– inflated self-esteem or grandiosity
– decreased need for sleep (e.g., feels rested after only 3 hours of sleep)
– more talkative than usual or pressure to keep talking
– flight of ideas or subjective experience that thoughts are racing
– distractibility (i.e., attention too easily drawn to unimportant or irrelevant external stimuli)
– increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation
– excessive involvement in pleasurable activities that have a high potential for painful consequences (e.g., engaging
in unrestrained buying sprees, sexual indiscretions, or foolish business investments)
•
C. The episode is associated with an unequivocal change in functioning that is uncharacteristic of the person when not
symptomatic.
•
D. The disturbance in mood and the change in functioning are observable by others.
•
E. The episode is not severe enough to cause marked impairment in social or occupational functioning, or to necessitate
hospitalization, and there are no psychotic features.
•
F. The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication, or
other treatment) or a general medical condition (e.g., hyperthyroidism).
Note: Hypomanic-like episodes that are clearly caused by somatic antidepressant treatment (e.g., medication,
electroconvulsive therapy, light therapy) should not count toward a diagnosis of Bipolar II Disorder.
DSM IV Criteria for Cyclothymia
(Again for completeness)
•
•
•
•
•
•
A. For at least 2 years, the presence of numerous periods with hypomanic
symptoms and numerous periods with depressive symptoms that do not meet
criteria for a Major Depressive Episode. Note: In children and adolescents, the
duration must be at least 1 year.
B. During the above 2-year period (1 year in children and adolescents), the person
has not been without the symptoms in Criterion A for more than 2 months at a
time.
C. No Major Depressive Episode, Manic Episode, or Mixed Episode has been
present during the first 2 years of the disturbance. Note: After the initial 2 years (1
year in children and adolescents) of Cyclothymic Disorder, there may be
superimposed Manic or Mixed Episodes (in which case both Bipolar I Disorder and
Cyclothymic Disorder may be diagnosed) or Major Depressive Episodes (in which
case both Bipolar II Disorder and Cyclothymic Disorder may be diagnosed).
D. The symptoms in Criterion A are not better accounted for by Schizoaffective
Disorder and are not superimposed on Schizophrenia, Schizophreniform Disorder,
Delusional Disorder, or Psychotic Disorder Not Otherwise Specified.
E. The symptoms are not due to the direct physiological effects of a substance
(e.g., a drug of abuse, a medication) or a general medical condition (e.g.,
hyperthyroidism).
F. The symptoms cause clinically significant distress or impairment in social,
occupational, or other important areas of functioning.
DSM IV Criteria for Dysthymic D/O
•
•
•
•
•
•
•
•
A. Depressed mood for most of the day, for more days than not, as indicated either by subjective account
or observation by others, for at least 2 years. Note: In children and adolescents, mood can be irritable and
duration must be at least 1 year.
B. Presence, while depressed, of two (or more) of the following:
– poor appetite or overeating
– insomnia or hypersomnia
– low energy or fatigue
– low self-esteem
– poor concentration or difficulty making decisions
– feelings of hopelessness
C. During the 2-year period (1 year for children or adolescents) of the disturbance, the person has never
been without the symptoms in Criteria A and B for more than 2 months at a time.
D. No Major Depressive Episode has been present during the first 2 years of the disturbance (1 year for
children and adolescents); i.e., the disturbance is not better accounted for by chronic Major Depressive
Disorder, or Major Depressive Disorder, In Partial Remission. Note: There may have been a previous Major
Depressive Episode provided there was a full remission (no significant signs or symptoms for 2 months)
before development of the Dysthymic Disorder. In addition, after the initial 2 years (1 year in children or
adolescents) of Dysthymic Disorder, there may be superimposed episodes of Major Depressive Disorder, in
which case both diagnoses may be given when the criteria are met for a Major Depressive Episode.
E. There has never been a Manic Episode, a Mixed Episode, or a Hypomanic Episode, and criteria have
never been met for Cyclothymic Disorder.
F. The disturbance does not occur exclusively during the course of a chronic Psychotic Disorder, such as
Schizophrenia or Delusional Disorder.
G. The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a
medication) or a general medical condition (e.g., hypothyroidism).
H. The symptoms cause clinically significant distress or impairment in social, occupational, or other
important areas of functioning.