Serotonin transporter linked promoter (polymorphism) in the serotonin transporter gene may be associated with antidepressant-induced mania in bipolar disorder

Objective Several pharmacogenetic studies suggest that response to pharmacotherapy in bipolar disorder may be mediated by genetic factors. The aim of this study was to investigate further the association of the genetic variations of the serotonin transporter (5-HTT) gene with antidepressant-induced mania, already reported in recent studies. We also studied the possible association of these genetic variants with diagnosis expression and treatment response to lithium therapy. Methods The sample consisted of 103 and 85 outpatients with diagnosis of bipolar and unipolar disorder, respectively, and 101 controls. Two described polymorphisms of the 5-HTT, the variable number of tandem repeat (VNTR) and serotonin transporter linked promoter (5-HTTLPR) polymorphisms, were genotyped using standard procedures. Results The association analysis performed showed a significantly higher rate of homozygous s/s genotype for 5-HTTLPR among patients with a history of antidepressant-induced mania (60% patients s/s versus 40% I/I, chi(2), P=0.04). No significant difference in the distribution of genotypes of the two polymorphisms was observed between the three groups. We found no significant association between these polymorphisms and lithium response. Conclusions The 5-HTTLPR polymorphism could be a useful contributor, among other clinical variables, to predict the risk for manic switches when a patient with bipolar disorder is treated with antidepressant drugs. The contribution of these genetic markers in diagnosis expression and treatment response to lithium is likely to be minor.