AUTHOR: Victor I. Reus, MD
Definition
Bipolar disorder is an episodic, recurrent, and frequently progressive condition in which the afflicted individual experiences at least one episode of mania, characterized by at least 1 wk of continuous symptoms of elevated, expansive, or irritable mood, in association with three or more of the following symptoms (four if irritability is the presenting mood):
- Decreased need for sleep
- Grandiosity or inflated self-esteem
- Pressured speech
- Flight of ideas or subjective sense of racing thoughts
- Distractibility
- Increased level of goal-directed activity
- Problematic behavior with a high potential for painful consequences
Most individuals with bipolar disorder also experience one or more episodes of major depression over their lifetimes or have symptoms of a depressive episode commingled with those of mania (mixed episode). Hypomanic episodes may also occur.1
Synonyms
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Epidemiology & Demographics
Prevalence (In U.S.)
0.4% to 1.6% (lifetime); bipolar spectrum disorders: 2.8%; approximately 25% attempt suicide, and suicide deaths occur 20× more frequently than in the general population
Genetics
- Concordance rates for monozygotic twins: 0.7 to 0.8; for dizygotic twins: 0.2
- Risk of affective disorder in offspring with one affected parent with bipolar disorder: 27% to 29%; with two affected parents: 50% to 74%
- Heritability estimate of 0.85
- No specific causal mutations have been identified, but cross-disorder studies indicate an overlap with genes associated with a risk for autism or schizophrenia and pleiotropic effects. Genome-wide association analyses and exome sequencing have suggested a role for AKAP11, CACNA1C, ANK3, TRANK1, ODZ4, ZNF804A, and KDM5B, among others, and have implicated ion channelopathies, immune and neuronal signaling, and histone methylation in pathogenesis of bipolar disorder. It is hypothesized that heritability derives from the additive effect of a number of common risk alleles in association with a few higher-risk deleterious variants. Copy number variations and epigenetic factors also moderate risk3,4
Physical Findings & Clinical Presentation
- Mania associated with:
- Psychomotor activation that is usually goal directed but not necessarily productive
- Increase in goal-directed activity and excessive involvement in activities leading to unexpected adverse outcomes
- Elevated, euphoric, and frequently labile mood
- Decreased need for sleep
- Flight of ideas with rapid, loud, pressured speech
- Psychosis often occurs (75%), with delusions, hallucinations, and/or formal thought disorder
- Depressive episodes resembling major depressive disorder (see “Depression, Major”), although usually of shorter duration and more frequent; atypical features (hypersomnia, prominent anxiety, weight gain) may be present
- Mixed states, characterized by activation, irritability, and dysphoria, also possible.
Key Diagnostic Criteria Distinguishing Bipolar I Disorder from Bipolar II Disorder:
Manic Episode (Bipolar I Disorder)
- Distinct period during which there is an abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently increased goal-directed activity or energy lasting at least 1 wk (or less if hospitalization is required).
- Must be accompanied by at least three of the following symptoms (four if mood is only irritable): Inflated self-esteem or grandiosity, decreased need for sleep, pressured speech, racing thoughts, distractibility, increased involvement in goal-directed activity or psychomotor agitation, excessive involvement in pleasurable activities with a high potential for painful consequences.
- Symptoms do not meet criteria for a mixed episode.
- Disturbance must be sufficiently severe to cause marked impairment in social or occupational functioning or to require hospitalization, or it is characterized by the presence of psychotic features.
- Symptoms not due to direct physiologic effect of medication, general medication condition, or substance abuse, although if they persist after a direct condition is addressed, a primary bipolar condition should be considered.5
Hypomanic Episode (Bipolar II Disorder)
- Distinct period during which there is an abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently elevated activity or energy lasting at least 4 consecutive days.
- Must be accompanied by at least three of the following symptoms (four if mood is only irritable): Inflated self-esteem or grandiosity, decreased need for sleep, pressured speech, racing thoughts, distractibility, increased involvement in goal-directed activity or psychomotor agitation, excessive involvement in pleasurable activities with a high potential for painful consequences.
- Hypomanic episodes must be clearly different from the person’s usual nondepressed mood, and there must be a clear change in functioning that is not characteristic of the person’s usual functioning; consider using checklist (HCL-32) for accuracy.
- Changes in mood and functioning must be observable by others. In contrast to a manic episode, a hypomanic episode is not severe enough to cause marked impairment in social or occupational functioning or to require hospitalization, and there are no psychotic features.
- Symptoms not due to direct physiologic effect of medication, general medication condition, or substance abuse.
Etiology
- Abnormalities of GABAA and G protein-coupled receptor and membrane function, calcium dysregulation6
- Alteration of cAMP, MAP kinase, protein kinase C, arachidonic acid cascade, and glycogen synthase kinase-3 signal transduction pathways; mitochondrial dysfunction
- Alteration in cell survival pathways, glial and neuronal death and loss of neuroplasticity; proposed biomarkers include BDNF and measures of inflammation, oxidative stress, and endothelial function7
