Bipolar Disorder in DSM-IV
• Bipolar I disorder: manic episode(s)
or mixed episode(s) plus MDE(s)
• Bipolar II disorder: major depressive
episode(s) plus hypomanic episode(s)
• Cyclothymia: hypomanic symptoms
plus depressive symptoms
Bipolar Disorders: DSM-IV Nosology
Criteria BPD I BPD II Cyclothymia
Mania Required No No
Hypomania Possible Required No
Major depression Possible Required No
Mixed state Possible No No
Manic Episode: Diagnostic Criteria
• Elevated, expansive, or irritable mood for
1 week or longer, plus 3 or more of the
following
– Inflated self-esteem or grandiosity
– Decreased need for sleep
– Pressured speech
– Racing thoughts/flight of ideas
– Distractibility
– Psychomotor agitation/increased goal-directed
activity
– Excessive involvement in high-risk activities
Manic Episode:
Differential Diagnoses
Differential diagnosis Consider if . . .
Mood disorder due to a Major medical condition present
general medical
condition First episode at >50 years of age
Symptoms in context of intoxication
Substance-induced or withdrawal
mood disorder History of treatment for depression
Mood disturbance not severe
Hypomanic episode enough to require hospitalization
or impair functioning
Mixed episode Manic episode and MDE in 1 week
Manic Episode:
Differential Diagnoses (cont.)
Differential diagnosis Consider if . . .
AD/HD Early childhood mood disturbance onset
Chronic rather than episodic course
No clear onsets and offsets
No abnormally elevated mood
No psychotic features
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders
(DSM-IV). 4th ed. 1994.
Major Depressive Episode:
DSM-IV Criteria
• Depressed mood and/or loss of interest
or pleasure 2 weeks duration
• Associated symptoms
– Physical: insomnia/hypersomnia,
appetite/weight change, decreased energy,
psychomotor change
– Psychological: feelings of guilt or
worthlessness, poor
concentration/indecisiveness, thoughts
of death/suicidal intentions (SI)
…and 4 of the following symptoms
• Physical • Psychological
– Sleep disorder – Low self
– Appetite change esteem/guilt
– Fatigue – Poor concentration/
indecisiveness
– Psychomotor
retardation – Thoughts of
death/SI
Mixed Episode: Diagnostic Criteria
• Criteria met for both manic episode + MDE
for 1 week
• Symptoms
– Are sufficient to impair functioning
or
– Necessitate hospitalization
or
– Are accompanied by psychotic features
Bipolar Disorders: Epidemiology
Characteristics BPD I BPD II
Prevalence 1.6% 0.5%
Ethnic/racial
differential None None
Gender
differential M=F F›M (?)
Bipolar Disorders: Epidemiology
Characteristics BPD I BPD II
Course Recurrent in Hypomanic episodes
>90% of cases in BPD II immediately
precede or follow
MDEs in 60% to
70% of cases
First-degree First-degree relatives
Familial relatives have may have increased
pattern increased rates of rates of BPD I, BPD
BPD I, BPD II, II, and MDD
and MDD
Epidemiology
• Peak age of onset: adolescence through early
20s
– Onset of first manic episode after age 40 years is
“red flag” to consider substance use or general
medical condition
• Seasonal variation
– Depression more common in spring and autumn
– Mania more common in summer
Diagnostic Dilemmas:
Unipolar Versus Bipolar
No evidence of hypomania,
Unipolar cyclothymia, hyperthymic personality,
or family history of BPD
BPD I 1 manic episode
Recurrent major depression with
BPD II
hypomania and/or cyclothymic
temperament
Recurrent major depression without
BPD NOS
spontaneous hypomania but often
with hyperthymic temperament
and/or family history of BPD
Etiology
Heritability
• Evidence for heritability is much stronger
for bipolar than for unipolar disorders
• Specific genetic association has not been
consistently replicated
EVIDENCE FOR HERITABILITY OF
BIPOLAR DISORDER
• Family Studies- First degree relatives are 8
to 18 times more likely to have Bipolar I
• 2 to 10 times to have MDD.
• Risk is 25% if one parent has illness, and
50% to 75% with both parents affected
FAMILY STUDIES
• The majority of individuals with bipolar disorder
have a positive family history of some type of
mood disorder
• About 50% of all bipolar I patients have at least
one parent with a mood disorder
ADOPTION STUDIES
• Prevalence of bipolar disorder in adopted away
offspring corresponds to rates in biological, but
not adoptive relatives
• Twin Studies- Concordance rate in MZ
twins is 33 to 90%, in DZ is 5 to 25%
Cognitive Deficits
• Working memory
• Sustained attention
• Abstract reasoning
• Visuomotor skills
• Verbal memory
• Verbal fluency
• Cognitive flexibility
• General cognitive functioning
Potential Explanations
for Cognitive Deficits
• Iatrogenic or Alcohol use
• Temporary functional changes
• Degenerative brain changes
• Permanent structural lesions
• Permanent functional alterations of neural
networks underlying affect and cognition
Alcohol Use
• Alcohol use occurs in 30-50% of cases
• Impairs memory and executive functioning
• Gorp et al (1998)
– Compared BP only, BP + AD, Control
– BP + AD > BP only for cognitive impairment
– No difference between Control and BP only
• Other studies have reported cognitive
deficits in non substance abusing BP
patients
Iatrogenic
• Lithium
– Memory and psychomotor functioning
• Valproate and Carbemazepine
– Attentional deficitis
• Neuroleptics
– Sustained attention
– Visuomotor speed deficits
• Benzodiazapines
– Memory
• Crews et al.
– Performance on WCST negatively related to years of exposure
to antipsychotic drugs
Questions
• Some evidence indicates that Lithium exerts a
neuroprotective effect on neuronal tissue
– Are studies indicating adverse effects of lithium not
accounting for complex combinations of meds?
• Could we even study this issue empirically??
– Ethics
– Generalizability
Temporal Functional Deficits
• Are cognitive deficits specific to depressive or manic states?
• Depression
– Decreased dorsal prefrontal cortex and anterior cingulate gyrus
activation
– Increased ventral prefrontal cortex activation
– Reductions in left hemisphere activity
• Mania
– Opposite pattern
– Decreased ventral and increased dorsal activity of the prefrontal cortex
– Reductions in right hemisphere activity
• Remission of depressive symptoms associated with increased blood
flow to dorsolateral and medial prefrontal cortex
• Distractibility and behavioral dysregulation
during mania
– Heightened left hemisphere prefontal corticol activity
• Attentional deficits accompanying depression
– Right hemisphere disturbance of dorsal prefrontal
cortex, cingulate gyrus, parlimbic cortex
Summary
• Authors contend (Savitz et al, 2005) that
functional disturbances have a
neurodevelopmental and possibly genetic
etiology that may be exacerbated by mood
disturbances