No Effect of Serotoninergic Gene Variants on Response to Interpersonal Counseling and Antidepressants in Major Depression

Background: Gene variants within the serotonin pathway have been associated with major depressive disorder (MDD) treatment outcome, however a possible different modulation on pharmacological or psychological treatments has never been investigated. Method: a multi-center trial enrolled 160 MDD patients randomized to either inter-personal counseling (IPC) or antidepressants. The primary outcome was remission at week 8. Five serotoninergic polymorphisms were investigated (COMT rs4680, HTR1A rs6295, HTR2A rs2224721, HTR2A rs7997012 and SLC6A4 rs421417). Results: IPC (n=43) and antidepressant (n=117) treated patients did not show any difference in remission rates at week 8 (corrected for baseline severity, age and center). None of the studied gene variants impacted on response and remission rates at week 8 neither in the IPC nor in the antidepressant group. An analysis of the whole sample showed a trend of association between rs7997012 AA genotype and a better treatment outcome. Conclusion: Our study confirms that IPC is an effective psychological intervention comparable to antidepressant medications in mild-moderate MDD. Polymorphisms related to the serotonin system did not exert a major effect on clinical outcomes in none of the treatment groups.