Lecture 8 - Bipolar Disorder

Question 1

DSM-5 Diagnosis of Bipolar

Answer 1

• Diagnosed based on the presence of a
  manic episode, lasting at least one week
  (most of the day, nearly every day) (except if hospitalized (could last less time when treated))
• Must be distinct period– i.e., distinct
  change from normal functioning
• Manic episode can consist of “elevated,
  expansive mood,” or “extreme irritability.”
• Persistently increased goal-directed
  activity or energy A lot of motivation, engagement with the world, start lots of projects
• If only irritable, need to meet more
  criteria.
• Inflated self-esteem or grandiosity
• Decreased need for sleep:
• Irritability often stems from inability to down-regulate/
  slow down.
• More talkative than usual:
• Pressured speech
• Flight of ideas/racing thoughts
• Jump from one idea to the next
• Appears similar to loose associations in Schizophrenia. Thoughts still make sense (unlike schizophrenia), but rapidly jump
• Thoughts are racing and they can’t keep up.
• Distractability:
• Reported or Observed
• Can contribute to the flight of ideas
• Sometimes leads to diagnostic difficulties with ADHD
• Increase in goal-directed activities:
• Can also be social
• Talk to strangers, call at all hours of the night,
  working on several projects at once (but never finish).
• Increased libido (along with impulsivity can contribute to infidelity, risky behaviour, divorce…)
• More active or agitated
• Can’t sit still
• Excessive involvement in pleasurable activities
  with a high potential for painful consequences:
• Shopping sprees, foolish business investments,
  sexual indiscretions.
• Not attributable to physiological effects of a
  substance (e.g., drugs) or another medical
  condition
• Overlaps with several other disorders,
  making differential diagnosis difficult.
• Need MARKED impairment for diagnosis:
• Hospitalization
• Psychotic features
• Extreme impairment in several domains
  (work, family, etc.)
• Distress NOT a factor in mania– poor
  insight and often feel very little pain.

Question 2

Forms of Bipolar Disorder

Answer 2

Don’t need both mania and depression (can be just mania or both… but not just depression)

• Bipolar I: mania plus episodes of MDD
  (but can get diagnosis before experience depression)
• Bipolar II: HYPOmania and MDD
• Hypomania same symptoms as mania, milder.
• No hospitalization
• No psychosis
• Mood is out of normal range, but not necessarily
  distressing
• Often very fun!
• Stimulus-seeking
• Causes some impairment, but not so extreme
• Cyclothymia
• Hypomania and short depressive episodes
• Chronic pattern, less severe
• LOTS of highs and lows
• More extreme than normal mood fluctuations
• M = F
• Often don’t seek treatment
  – women more likely
• At increased risk for Bipolar I
• Antidepressant meds can be a trigger
  -2 or more years of this pattern
• Specifier: Rapid Cyclers:
• 4 or more episodes within a year
• Can be either kind of episode
• More likely to be female
• Predicts poor response to treatment
• Mood stabilizers often ineffective
• NOT a stable trait– rather a phase that some will
  pass through.
  -have earlier onset
  -Continuous = no free interval between episodes (idk if it always is continuous though)

Question 3

Psychotic symptoms of bipolar

Answer 3

• Mood Congruent vs. Mood Incongruent psychotic symptoms
  Mood congruent: consistent with someone’s mood state (makes sense with mania or depression)
  Mood incongruent: inconsistent with someone’s mood state

Mood congruent in mania: am Jesus, I am a billionaire…
Mood congruent in depression: the world has been destroyed, I have committed a sin

Mood incongruent in mania:
 Thought insertion
 Mind control

Mood incongruent in depression:
 Anything happy
 This is rare

 Psychotic symptoms raise serious differential diagnosis questions.
 Current DSM-5 resolution:
- If psychotic symptoms occur during a manic or depressive episode, then qualifies as a
MOOD DISORDER (w/ psychosis)
- If occur outside mood episode, usually schizoaffective diagnosis

Question 4

Epidemiology of Bipolar Disorder

Answer 4

Bipolar I and II
 Lifetime prevalence between 2-4% for EITHER
BIPOLAR I OR II
 Prevalence does not seem to differ as a
function of sex, culture, countries, parts of the
world
- Rates fairly stable
 Some evidence prevalence may be higher in
certain subgroups
 Used to think high SES = greater prevalence,
- Probably diagnostic bias
- Low SES more likely to be diagnosed with
Schizophrenia
- Rates of Bipolar much higher among artists,
poets, writers

Cyclothymia
* Prevalence closer to 4-5%
* Contrast with MDD, 17%
lifetime prevalence

Unipolar mania (only experiencing mania, not mdd)
* Unipolar mania has been reported in community
studies of mania
* 25% to 33% of bipolar I patients
* 1-2% in general population
* However, if you follow unipolar mania for long
enough, the majority (20/27, or 74%) had at least
one episode of depression during follow-up
* Not clear if unipolar mania is stable over the life
course or whether most bipolar I patients, if
followed long enough, eventually develop a
depressive episode.

Unipolar (MDD)/bipolar distinction
* MDD 10-20 x more common than Bipolar.
* Differ in gender distribution:
- Bipolar: M≈F
- Unipolar: 2F = 1M
* Differ in course:
- Bipolar– earlier onset
- Bipolar– more episodes
- Bipolar– more pernicious course

Question 5

Course of Bipolar Disorder

Answer 5

• Takes average of 6 to 10 years for an individual
  with bipolar disorder to receive correct
  diagnosis and appropriate treatment
• Misdiagnosed consult an average of four
  physicians prior to receiving an accurate
  diagnosis
• Close to 60% of individuals with bipolar
  disorder initially misclassified as having MDD
• In general, more likely to seek treatment when
  depressed

Treatment response differs:
* Mood stabilizers (lithium) and anticonvulsants for bipolar
* Anti-depressants (e.g., tricyclics,
SSRIs) for unipolar
* Anti-depressants can trigger manic
episodes in bipolar
-explains why a lot of people with bp don’t want to take meds… mania (the fun part) gets stabilized but doesn’t work for the depression part (and anti-depressants can trigger mania)

• Age-of-onset:
• 20-30
• ½ time 1st episode is manic
• ½ time 1st episode is depressed
• 5-10% of people who present with a
  history of only depression will
  convert to bipolar
• Particularly if younger age,
  heightened guilt, psychomotor
  retardation, and a family history of
  bipolar
• Episodes typically last about 2 months
• Previously 8 months, prior to effective treatments
• Poor prognostic indicators (indication treatment might not work as well):
• Mixed states
• Rapid cycling
• Relapse rate– 7-9 times over lifetime

Suicide in bipolar
* Risk of death by suicide are 15 X the general population
* 4 X patients with major depressive disorder
* Some estimates of inpatients with bipolar suggest 11% die by suicide
* Risk factors for death by suicide:
- younger age
- recent illness onset
- male gender
- prior suicide attempts (SAs)
- a family history of suicide
- comorbid alcohol or substance abuse
- rapid cycling course
- social isolation
* MOST of these are associated with increased risk for death by suicide across all populations, not specific

Question 6

Etiology of Bipolar Disorder

Answer 6

Environmental: Stress and Adversity in
Bipolar
* Stress appears to increase in the 1st 6 months prior to
an episode
* Frequently relapse following a stressful experience
* Sheri Johnson (UC Berkeley)
* Particular class of stressors important in mania:
- Goal-attainment events
- Significantly associated with manic episodes.
- When achieve a goal, become very happy;
subsequently dysregulated; spiral into mania.

How does stress get “into” the brain?
* Kindling:
* Graham Goddard (1967)
* stimulate areas of the brain
repeatedly w/ electricity, seizures
develop
* Over time, requires lower doses of
electricity to provoke a seizure
* Eventually happens with no
electricity
* Robert Post (George Washington University)
* Applied this theory to Bipolar Pts.
* 1
st episode of Bipolar requires a lot of stress
* 2
nd episode requires less stress
* 3
rd episode even less
* Eventually, don’t need stressors– episodes occur on
their own.

Sleep disruption
* Sleep deprivation a powerful predictor of
mania
* Less sleep on day N predicts increases in
manic symptoms on day N+1
* Exposure to bright light, which can change
circadian rhythms, can trigger of manic
symptoms

Question 7

Neurobiology of Bipolar Disorder

Answer 7

Striatum
* Ventral Striatum
* Striatum is a central part of basal
ganglia
- Facilitate voluntary
movement
- Reward processing
* Esp. nucleus accumbens
* Reward & reinforcement

Striatum in Bipolar
* Enlarged in men and women with bipolar
disorder
* Compare first-and multiple episode
bipolar and HC
* Enlargement in both affected and
unaffected monozygotic twins discordant
for bipolar disorder

Reward in Bipolar
* Abnormally elevated activity within the VS during:
- reward anticipation
- reward consumption
- to reward-predictive cues
* A failure of prefrontal regions to effectively down-regulate
VS responses
* Recent evidence:
- Reward consumption-related activation more prominent in BP-I
- Abnormalities in reward anticipation-related activation more
prominent in BP-II

Question 8

Treatment of Bipolar Disorder

Answer 8

Lithium
* Mid-nineteenth century, lithium was used to treat
many disorders
* Fell out of fashion
* Lobotomies became more common for bipolar
* John Cade, 1949
* Tranquilizing effects
* Began to use on his hospitalized bipolar patients
* For many years no consensus on how it works
* Deactivates an enzyme that interferes with circadian
clock
* Glutamate antagonist
* Recent evidence: appears to interrupt dopamine
signaling in the brain
* Very narrow therapeutic window
* Side effects:
- Thyroid and kidney problems
- Dehydration, weight gain, acne, thinning of hair, hand
tremors

(see slide of lithium levels in drinking water per country and suicide rates by country)