Pharmacogenetics of selective serotonin reuptake inhibitor response: A 6-month follow-up

Background: We previously reported the association between some genetic factors and short-term antidepressant outcome. In the present paper we investigated the same gene variants in a prospective 6-months naturalistic follow-up. Methods: The sample included 185 inpatients affected by recurrent major depression consecutively admitted to the Psychiatric Inpatient Unit of San Raffaele Hospital from 1998 to 2003 and prospectively followed for 6 months after their recovery. All the patients were undertaking continuation therapy. The functional polymorphism in the upstream regulatory region of the serotonin transporter gene (SERTPR), the tryptophan hydroxylase A218C substitution, a VNTR polymorphism located 1.2 kb upstream of the monoamine oxidase-A coding sequences, the CLOCK gene T3111C and the PER3exon15 gene T1940G substitutions were analysed, using PCR-based techniques. Results: No association was found between clinical variables and relapses; subjects showing TT genotype at CLOCK gene tended to relapse within 6 months after recovery more than TC and CC subjects taken together. A non-significant tendency of SERTPR* s/s subjects to a minor frequency of relapse was also observed. Conclusion: Some subjects showing remission after acute treatment relapsed within 6 months, despite undertaking a maintenance treatment; the causes could be heterogeneous, but CLOCK gene variants may influence the outcome.