Oligogenic approaches to modelling onset of action of antidepressants

It is currently still a major unsolved clinical problem to make predict individual response to treatment with antidepressants. Therefore, we evaluate in our molecular genetic study of antidepressant drug response the clinical data of patients treated with pharmacologically different antidepressants and placebo in order to model the time course of clinical improvement. Onset of improvement and response to therapy is determined for each individual patient through survival-analytical methods. Genotyping for 120 candidate genes allows us to search for oligogenic configurations of loci that explain a major proportion of the observed variation in the time characteristics of recovery.

Preliminary results of our pilot study of 105 patients treated with antidepressants and genotyped for 72 candidate genes suggested a genetic predisposition to the time characteristics of antidepressant drug response. Our multivariate pattern recognition algorithm revealed a configuration of 23 loci that enabled discrimination between early improvers, late improvers, and non-improvers at a rate of >75% correctly classified patients.