137: Bipolar Mood Disorder

Key Points

• Disease summary:

  • Bipolar mood disorder (BP) is characterized by severe disturbances of mood that may include depression, mania or hypomania, or irritability. Manias are pathologically energized states with misguided volition and behavior in a mood state of intoxicating euphoria (or irritability) and depression. Depression consists of pathologically compromised energy and volition with a slowing of bodily functions, most prominently cognition and concentration. The disturbed mood may appear during distinct periods or as a more sustained disturbance. The underlying pathophysiology of the disorder is an interaction between multiple interacting genetic loci and environmental factors which trigger the disease.

• Differential diagnosis:

  • Depression with or without psychotic features, schizophrenia, personality disorder, substance or alcohol abuse, attention deficit hyperactivity disorder (ADHD), and anxiety disorders. Some medical disorders (hyperthyroidism, treatment with steroids among others) may mimic BP.

• Monogenic forms:

  • No single gene form of BP has been identified.

• Family history:

  • Positive family history of both unipolar and bipolar depression is noted in first-degree relatives and risk of any mood disorder increases as the number of close relatives increases. History of past diagnosis of ADHD is common possibly because of the overlapping symptoms between the two disorders. Increased history of consanguinity among parents of BP patients has been reported.

• Twin studies:

  • Concordance rate for monozygotic twins is reported to be in the range of 70% and the dizygote concordance in the range of 20%. This clearly supports the genetic basis of bipolar disorder. Based on this and additional genetic research the heritability has been estimated to be 85%.

• Environmental factors:

  • Environmental factors may include history of trauma and abuse (physical and sexual abuse), substance abuse disorders, temperamental factors, and the postpartum period. Different environmental factors may affect the onset and the recurrence of the disorder.

• Genome-wide associations:

  • There are no genes with risk variants that currently have clinical relevance for the actively managed patient with bipolar disorder. Genome-wide association studies (GWASs) have identified several risk genes and a number of them have been replicated in independent studies in BP. These include ANK3 which regulates voltage-gated sodium channels, CACNA1C (a voltage-gated calcium channel gene), and SYNE1 involved in neurogenesis and synaptic clustering. The calcium channel pathway evidence was confirmed and a new locus at ODZ4 was identified.

• Pharmacogenomics:

  • There are no laboratory or other tests that are recommended as standard of care for the assessment and management of bipolar disorder. The efforts in pharmacogenetics have identified several variants in genes that code for enzymes that commonly metabolize psychotropic medications. These include variants in genes that code for the enzymes CYP2D6, CYP2C19, and CYP3A4. However, the clinical relevance beyond good clinical knowledge of the patient and pharmacologic treatment remains to be determined.

Diagnostic Criteria and Clinical Characteristics

Diagnosing BP

The Diagnostic and Statistical Manual IV (DSM IV) describes four different forms of BP disorder: BP I, BP II, BP NOS, and cyclothymia. Essential criterion for ...