Serotoninergic and dopaminergic genes in bipolar disorder and response to treatments in bipolar depression. Investigation on a well-characterized naturalistic sample

Inheritable factors are known to play an important role in the risk for Bipolar disorder (BD) as well as response to pharmacological treatment. In the present study, we further investigated four candidate genes for BD and response to pharmacological treatments, in a naturalistic sample of 131 patients and 6S healthy controls. Patients were characterized for socio-demographic and clinical variables, including substance abuse, axis II personality disorders, temperamental traits and social adjustment. Patients meeting criteria for a depressive episode were followed for 6-months of pharmacological treatment (n=92). Polymorphisms within the genes for Serotonin receptor 2A (5HTR2A), trypthophan hydroxylase 1 (TPH1), Dopamine receptor D2 (DRD2) and Dopamine receptor D4 (DRD4), were analyzed for the present study. 5HTR2A, DRD2 and DRD4 variants were not associated to BD, response to treatment and other variables considered in the study. A haplotype in TPH1 (rs1800532-rs7933505) showed a trend of association with BD, though non-significantly considering correction for multiple testing. Taking into account limitations linked to the small sample size and the naturalistic approach in recruitment and treatment of BD patients, this study does not support an involvement of the genes here considered in BD and medium- term outcome of bipolar depression. Further studies are required to clarify the role of TPH1, particularly of the less investigated rs7933505 variant in BD.