Genetics of bipolar disorder

Bipolar disorder (also known as manic depressive illness) is a complex gene tic disorder in which the core feature is pathological disturbance in mood (affect) ranging from extreme elation, or mania, to severe depression usual ly accompanied by disturbances in thinking and behaviour. The lifetime prev alence of 1% is similar in males and females and family, twin, and adoption studies provide robust evidence for a major genetic contribution to risk. There are methodological impediments to precise quantification, but the app roximate lifetime risk of bipolar disorder in relatives of a bipolar proban d are: monozygotic co-twin 40-70%; first degree relative 5-10%; unrelated p erson 0.5-1.5%. Occasional families may exist in which a single gene plays the major role in determining susceptibility, but the majority of bipolar d isorder involves the interaction of multiple genes (epistasis) or more comp lex genetic mechanisms (such as dynamic mutation or imprinting). Molecular genetic positional and candidate gene approaches are being used for the gen etic dissection of bipolar disorder. No gene has yet been identified but pr omising findings are emerging. Regions of interest identified in Linkage st udies include 4p16, 12q23-q24, 16p13, 21q22, and Xq24-q26. Chromosome 18 is also of interest but the findings are confusing with up to three possible regions implicated. To date most candidate gene studies have focused on neu rotransmitter systems influenced by medication used in clinical management of the disorder but no robust positive findings have yet emerged. It is, ho wever, almost certain that over the next few years bipolar susceptibility g enes will be identified. This will have a major impact on our understanding of disease pathophysiology and will provide important opportunities to inv estigate the interaction between genetic and environmental factors involved in pathogenesis. This is likely to lead to major improvements in treatment and patient care but will also raise important ethical issues that will ne ed to be addressed.