Pharmacogenetics of Bipolar Disorder

Firoza      Mamdani; Iris   Jaitovich   Groisman; Martin      Alda; Gustavo      Turecki

Abstract

Bipolar disorder (BD), or manic-depressive illness, is a psychiatric disorder characterized by episodes of major depression and mania. The importance of genes in the etiology of BD has been substantiated through family, twin and adoption studies. BD is treated at both the prophylactic and episodic levels with lithium being one of the most common forms of prophylactic treatment. Recently, pharmacogenetics has come to play an active role in the elucidation of genetic factors that may play a role in modulating drug response. This strategy has provided hope for advancements in understanding the genetics of BD. This review encompasses several studies that either have used populations of lithium responders, responders to selective serotonin re-uptake inhibitors or responders to antidepressants in general to carry out linkage or association studies. There have been positive results found associating a polymorphism in the phospholipase C gamma 1 gene with BD and several variants of the serotonin transporter gene have been related either to worse response or nonresponse, as well as, linkage studies providing evidence for new loci to explore. Although data examining the pharmacogenetics of BD remain scarce, it is clear that this is a promising avenue of investigation. Whether used to define genetically more homogeneous populations or to search for genetic predictors of drug response, pharmacogenetic strategies in BD have produced interesting results thus far and further investigation is warranted.

Keywords: bipolar disorder, pharmacogenetics, lithium, antidepressants

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