Bipolar Disorder

Definition

Bipolar disorder is a mood disorder characterized by recurrent episodes of mania (or hypomania) and depression. Includes Bipolar I (full manic episodes), Bipolar II (hypomanic + depressive episodes), and Cyclothymia. Diagnosed per DSM-5 / ICD-11 criteria.

Symptoms

Manic/hypomanic episodes:

Elevated or irritable mood
Decreased need for sleep
Grandiosity or inflated self-esteem
Racing thoughts, pressured speech
Increased goal-directed activity
Impulsivity and risky behavior

Depressive episodes:

Overlap with MDD symptom profile (see Depression)

Heritability and Etiology

Bipolar disorder has high heritability (~60–85%). Considerable genetic and neurobiological overlap with schizophrenia. Risk architecture is complex and polygenic.

Epigenetic Mechanisms

Overlap with SCZ epigenome: Genome-wide DNA methylation studies of postmortem SCZ and bipolar brains (with psychosis) show a similar degree of subtle but significant methylation changes at many gene promoters. (Established: postmortem studies.)
HLA9 multi-tissue methylation: HLA9 (HLA complex group 9) shows aberrant methylation in postmortem brain, peripheral blood, and sperm of bipolar patients. The mechanism driving this multi-tissue epigenetic dysregulation is unknown. (Unusual finding; significance unclear.)
GAD1 in hippocampus: GAD1 shows altered DNA methylation in hippocampus in bipolar disorder, paralleling SCZ findings. (Postmortem; supports shared GABAergic pathology.)
H3K4 methylation regulators as genetic risk: Regulators of H3K4 methylation emerged as one of the strongest genetic risk categories for bipolar disorder in GWAS data (Psychiatric Genetics Consortium 2015). This is a direct link between epigenetic machinery genes and disorder risk. (Established: genetic data.)

Relationship to Schizophrenia

Bipolar disorder and SCZ share: genetic risk loci, neurobiological features, some treatment approaches (antipsychotics used in both), and epigenetic dysregulation patterns. They are increasingly viewed as overlapping on a psychosis spectrum rather than fully discrete entities.