The role of serotonin transporter protein gene in antidepressant-induced mania in bipolar disorder: preliminary findings.

Background The occurrence of mania during antidepressant treatment is a key issue in the clinical management of bipolar disorder (BP). The serotonin transporter (5-HTT) is the selective site of action of most proserotonergic compounds used to treat bipolar depression. The 5-HTT gene ( SLC6A4 ) has 2 known polymorphisms. The aim of this study was to investigate the role of the SLC6A4 variants in the pathogenesis of antidepressant-induced mania in BP. Methods Twenty-seven patients with a DSM-IV diagnosis of BP I or II, with at least 1 manic or hypomanic episode induced by treatment with proserotonergic antidepressants (IM+ group), were compared with 29 unrelated, matched patients with a diagnosis of BP I or II, who had been exposed to proserotonergic antidepressants without development of manic or hypomanic symptoms (IM− group). The 2 known polymorphisms of the SLC6A4 were genotyped, and allelic and genotypic association analyses were performed. Results With respect to the polymorphism in the promoter region ( 5HTTLPR ), IM+ patients had an excess of the short allele (n = 34 [63%]) compared with IM− patients (n = 17 [29%]) (χ 2 1 , 12.77; P 2 2 , 12.43; P = .002). No associations were found for the polymorphism involving a variable number of tandem repeats. Conclusion If these results are replicated, the 5HTTLPR polymorphism may become an important predictor of abnormal response to medication in patients with BP.