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  Disease summary:

  
  
  
  
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    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.

  
  
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  Differential diagnosis:

  
  
  
  
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    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.

  
  
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  Monogenic forms:

  
  
  
  
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    No single gene form of BP has been identified.

  
  
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  Family history:

  
  
  
  
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    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.

  
  
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  Twin studies:

  
  
  
  
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    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%.

  
  
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  Environmental factors:

  
  
  
  
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    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.

  
  
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  Genome-wide associations:

  
  
  
  
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    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.

  
  
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  Pharmacogenomics:

  
  
  
  
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    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.

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 BP I is the presence of at least one manic or one mixed episode. For BP II, one depressive episode and one hypomanic episode are required and for BP NOS the number or the duration of symptoms are insufficient to diagnose either BP I or BP II. Cyclothymia is a milder form of the illness, characterized by shifting back and forth between mild depression and hypomania for a 2-year period; however, the symptoms are not severe enough to meet the criteria for other forms of BP.

A thorough psychiatric and medical history is necessary for making accurate diagnosis. Standardized diagnostic interviews (SDIs) may be used in some instances.

There is no laboratory or psychologic test available for diagnosing these disorders. However, because of relatively high rates of comorbidity with psychiatric and medical disorders and because some general medical conditions may mimic BP, any patient experiencing the first episode of BP should receive a battery of laboratory tests (CBC with differential count, metabolic panel including electrolytes, thyroid function tests, liver function tests, and urine analysis and toxicology). Additional tests may be based on abnormal findings.

Contributing factors may include general medical conditions, medications with known association with mood disturbance, and alcohol and drug misuse. However, the symptoms of BP should not be directly related to these factors, to give an independent diagnosis of BP.

Psychosocial stress is commonly associated with the first episode and may be associated with recurrences. Symptoms may be incorrectly attributed as a reaction to stress, however, stressful events are best viewed as a precipitating or maintaining factors.

Brain imaging may be completed in some cases, especially when there is concern that space occupying lesions may be contributing to the pathology.

Absence of the following criteria is necessary:

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  The symptoms of BP should not be accounted for by, or superimposed on schizophrenia, schizoaffective disorder, schizophreniform disorder, psychosis NOS, or delusional disorder.

  
  
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  Symptoms should not be solely accounted for by a comorbid general medical disorder, medications with known mood effects and alcohol or illicit drugs. If the symptoms are related to one or more of these factors, the final diagnosis of BP should be deferred.

Clinical Characteristics

The central symptoms of BP are intermittent or chronic mood disturbance. Mood disturbance may include depression, elevated mood, and/or irritability presenting in different combinations. Additional symptoms include uncharacteristic changes in behavior, thought and speech, and rest-activity cycles. Cognitive deficits are not considered central to the illness. The symptoms may be cyclical with periods of complete or near-complete remission. BP is often missed in patients who may appear to be primarily depressed. Therefore, careful evaluation for BP is essential even in patients who present with symptoms of depression.