Genetic features of antidepressant induced mania and hypo-mania in bipolar disorder

Rationale and objectives: The present study investigated possible genetic association between some polymorpbisms possibly involved in antidepressant response and the occurrence of manic or hypo-manic switches during antidepressant treatment. Methods: We retrospectively examined 169 individuals with a diagnosis of bipolar disorder (BP) type I (n=103) and II (n=66), who presented at least one sudden manic or hypomanic episode (according to DSM IV criteria) during antidepressant therapy, that occurred within a period of 3 weeks from the beginning of the treatment and without any interposed period of well being ("manic switch"). They were compared with a sex, age, and ethnicity-matched group of 247 subjects, randomly selected from our pool of bipolar subjects, who never showed switches. We then randomly selected from the whole sample ("switched" and "not switched") a sub-sample of patients not under mood stabiliser treatment at the time of the index episode (65 "switched" and 117 "not switched") and compared them with a sex, age and ethnicity matched group of 133 subjects, randomly selected from our pool of major depressed patients, who did not present manic switches. The functional polymorphism in the upstream regulatory region of the serotonin transporter (SERTPR), tryptophan hydroxylase (TPH), G-protein beta 3 subunit (Gbeta3), monoamine oxidase A (MAO-A), catechol-O-ethyltransferase (COMT), serotonin receptor 2A (5HT2A), dopamine receptor D2 (DRD2) and dopamine receptor D4 (DRD4) gene variants were analysed using PCR-based techniques. Results and conclusions: The distribution of the genetic polymorphisms was not significantly different between switched and not-switched patients (P>0.006-Bonferroni corrected). Moreover, no significant difference was found between switched and not switched sub-samples and the sample of major depressed subjects. Further studies are required to investigate other possible related genetic variants influencing the timing of manic-depressive cycle.