Monoamine oxidase a and tryptophan hydroxylase gene polymorphisms: are they associated with bipolar disorder?

Most of the candidate gene studies in bipolar disorder have focused on the major neurotransmitter systems that are influenced by drugs used in the treatment of this disorder. The monoamine oxidase A (MAOA) and the tryptophan hydroxylase (TPH1, TPH2) genes are two of the candidates that have been tested in a series of association studies using unrelated or family-based controls. This review summarizes the existing association studies regarding these genes. Most of these studies were based on the unrelated case-control design with samples of 50 to 600 subjects. Regarding MAOA, three meta-analyses with partially overlapping samples supported a modest effect of this gene in bipolar disorder in female Caucasians. However, as several studies could not replicate these findings, more work is necessary to demonstrate unequivocally the involvement of MAOA in bipolar disorder and establish the biological mechanism underlying the genetic association. With respect to TPH1 and TPH2, the majority of studies did not provide evidence for an association between these genes and bipolar disorder. The genes are more likely to be related to suicidal behavior than to bipolar disorder.