The role of 5-HTTLPR polymorphism in antidepressant-associated mania in bipolar disorder

BackgroundThe occurrence of mania during antidepressant treatment is a key issue in the clinical management of bipolar disorder (BD). The serotonin transporter gene is a candidate to be associated with antidepressant-associated mania (AAM) in some patients. This gene has a polymorphism within the promoter region (5-HTTLPR) with two allelic forms, the long (L) and the short (S) variants.MethodsWe performed a case-control study to compare 5-HTTLPR genotype and allelic frequencies between 43 patients with a DSM-IV diagnosis of BD, with at least one manic/hypomanic episode associated with treatment with proserotonergic antidepressants (AAM+) and 69 unrelated, matched bipolar patients, who had been exposed to proserotonergic antidepressants without development of manic symptoms (AAM−). Furthermore, we performed this comparison between a subgroup of 23 AAM+ patients that, when they presented AAM, were not using mood stabilizer (AAM+⁎) and 25 AAM− patients who used antidepressant without the concomitant use of a mood stabilizer (AAM−⁎). 5-HTTLPR genotyping was performed using PCR.ResultsNo significant differences were found between AAM+ and AAM−. Within the subgroups, our results show that S-carriers (LS + SS Genotypes) are more prone to make a manic/hypomanic episode associated with antidepressant (P = 0.017).LimitationsOur study is retrospective.ConclusionsThe 5-HTTLPR polymorphism may be considered a predictor of abnormal response to antidepressant in patients with BP, but this action is influenced by the presence of a mood stabilizer. Such observations reinforce that a correct diagnosis of bipolarity before the beginning of the treatment is essential, mainly for S-carriers patients.