From molecular biology to pharmacogenetics: a review of the literature on antidepressant treatment and suggestions of possible candidate genes.

Pharmacogenetic studies in mood disorders are raising increasing interest, after the first findings of a significant association between antidepressant response and a functional polymorphism in the upstream regulatory region of the serotonin transporter gene (SERTPR). However, the results of published studies are not unequivocal. The reasons of these discordances could be various: the small samples, which could affect the power to detect a good effect size, the use of different and often not comparable scales and methodologies to assess the response rates. Notwithstanding all these limitations, the choice of candidate genes involved in antidepressant response is one of the crucial steps to target future research. In the present paper, we reviewed the literature concerning pharmacogenetic studies on antidepressant response. This analysis evidenced a number of studies consistently confirming the association of the SERTPR short variant with a poorer response to antidepressants, at least for the Caucasian samples. Further unreplicated positive findings included tryptophan hydroxylase (TPH), G-protein beta(3)-subunit (Gbeta(3)) and serotonin receptor 2A gene polymorphisms. Through the review, we also suggested possible candidate genes for future studies, which are involved in the main monoaminergic neurotransmitters pathways (norepinephrine, dopamine, serotonin), in substance P, neurokinines and glutamate systems, in the intracellular signal transduction pathway, in the phosphorylation process and in the control of the transcriptional activity system.