Bipolar disorder genetics

The precise etiology of bipolar disorder is unknown. Thought to be genetically based, bipolar disorder is influenced by a variety of factors that may enhance gene expression. These include trauma, environmental factors, anatomic abnormalities, exposure to chemicals or drugs, and others.3-5 Neurochemical abnormalities in bipolar disorder may be caused by these factors, as discussed further in the pathophysiology section. 

Results of family and twin studies suggest a genetic basis for bipolar disorder.4 The lifetime risk of bipolar disorder in relatives of a bipolar patient is 40% to 70% for a monozygotic twin and 5% to 10% for another first-degree relative. 

These data show that for three psychotic disorders (schizophrenia, bipolar disorder and unipolar depression) the genetic contribution is over 50% but for reactive depression (in response to a traumatic life event ) and tuberculosis, an infectious disease caused by a species of Mycobacterium, environmental factors account for over 90% of the variance. 

Both genetic and nongenetic factors play roles in the transmission of mood disorders. The familial nature of mood disorders is well established. Studies over the past 20 years have consistently documented higher rates of mood disorder in the relatives of individuals with major depression and bipolar disorder than in relatives of healthy controls [6,7], The familial aggregation of mood disorders is the outcome of both genetic and environmental factors. 

The concordance rate of mood disorders is 60-80% for monozygotic twins and 14-20% for dizygotic twins. Linkage studies suggest that certain loci on genes and the X chromosome may contribute to genetic susceptibility of bipolar disorder,... 

Schizophrenia and Bipolar Disorder Manifestation and Dilemma Faced by Genetic Studies in Psychiatry... 

One of the major limitations in studies of the genetics of behavioural disorders in children arises from the overlap with other conditions. For example, nearly 50% of the patients with ADHD also have co-morbid conduct disorders. In addition, a subtype of the disorder may exist in those children in which the disorder persists into adulthood. An additional problem arises from the overlap between ADHD and bipolar disorder this has been estimated to be as high as 16%. 

Bocchetta, A., Piccardi, M.P., Palmas, M.A., Chillotti, C., Oi, A., and Del Zompo, M. (1999) Family-based association study between bipolar disorder and DRD2, DRD4, DAT, and SERT in Sardinia. Am Med Genet 88 522-526. 

Kelsoe, J., Sadovnick, A., Kristbjarnarson, H., Bergesch, P., Mroczkowski-Parker, Z., Drennan, M., Rapaport, M., Flodman, P., Spence, M., and Remick, R. (1996). Possible locus for bipolar disorder near the dopamine transporter on chromosome 5. Am J Med Genet (Neuropsychiatr Genet) 67 533-540. 

Waldman, I.D., Robinson, B.E, and Feigon, S.A. (1997) Linkage disequilibrium between the dopamine transporter gene (DATl) and bipolar disorder extending the transmission disequilibrium test (TDT) to examine genetic heterogeneity. Genet Epidemiol 14(6) 699-704. 

GAD affects about 4 million Americans. It usually manifests after childhood and before a person reaches middle age. ft happens about twice as often in women as in men. Symptoms must persist for at least six months before a diagnosis of GAD may be made. In addition, GAD often occurs along with other psychiatric illnesses, such as depression or bipolar disorder, or with drug abuse, which probably leads to an underestimation of the amount of people affected by this disorder. There is some evidence that the disorder has a genetic component... 

It appears that a number of complications await the recovering bipolar patient after an episode of mania. For example, Lucas et al. ( 44) reported on a retrospective linear discriminant analysis of 100 manic episodes (1981 to 1985) during the recovery phase and found that the incidence of subsequent depression was 30% in the first month. Many episodes were transient, however, and did not necessarily require treatment. This phenomenon could be successfully predicted in 81% of cases in which there is a premorbid history of cyclothymia with either a personal or a family history of depression. The highly significant association between family history and postmanic depression again supports the hypothesis of a genetic basis for bipolar disorder. 

Although biological and genetic factors are undoubtedly important, they may not explain all the variance in the course and prognosis of a bipolar disorder. 

An important body of evidence from descriptive, clinical, and genetic sources finds that bipolar disorder is a separate entity from unipolar disorder (i.e., genetically the two variants breed true see also the section Mechanism of Action earlier in this chapter). When we pooled data from several studies that investigated bipolar or unipolar disorders, lithium was more effective than placebo in preventing relapse in bipolar, as well as unipolar, disorders ( Table 10-11 and Table 10-12). 

Bipolar disorder, once known as manic-depressive illness, was conceived of as a psychotic disorder distinct from schizophrenia at the end of the 19th century. Before that both of these disorders were considered part of a continuum. It is ironic that the weight of the evidence today is that there is profound overlap in these disorders. This is not to say that there are no pathophysiologically important differences or that some drug treatments are differentially effective in these disorders. According to DSM-IV, they are separate disease entities while research continues to define the dimensions of these illnesses and their genetic and other biological markers. 

The sequence, number, and intensity of manic and depressive episodes are highly variable. The cause of the mood swings characteristic of bipolar affective disorder is unknown, although a preponderance of catecholamine-related activity may be present. Drugs that increase this activity tend to exacerbate mania, whereas those that reduce activity of dopamine or norepinephrine relieve mania. Acetylcholine or glutamate may also be involved. The nature of the abrupt switch from mania to depression experienced by some patients is uncertain. Bipolar disorder has a strong familial component, and there is abundant evidence that bipolar disorder is genetically determined. 

Escamilla MA, Zavala JM Genetics of bipolar disorder. Dialogues Clin Neurosci 2008 10(2) 141. [PMID 18689285]... 

Goes FS, Sanders LL, Potash 3B The genetics of psychotic bipolar disorder. Curr Psychiatry Rep 2008 10 178. [PMID 18474212]... 

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