Antidepressant pharmacogenetics represents a stimulating, but often discouraging field. The present study proposes a combination of several methodologies across three independent samples. Genes belonging to monoamine, neuroplasticity, circadian rhythm and transcription factor pathways were investigated in two samples (n=369 and 88) with diagnosis of major depression who were treated with antidepressants. Phenotypes were response, remission and treatment-resistant depression. Logistic regression including appropriate covariates was performed. Genes associated with outcomes were investigated in the STAR*D (Sequenced Treatment Alternatives to Relieve Depression) genome-wide study (n=1861). Top genes were further studied through a pathway analysis. In both original samples, markers associated with outcomes were concentrated in the PPP3CC gene. Other interesting findings were particularly in the HTR2A gene in one original sample and the STAR*D. The B-cell receptor signaling pathway proved to be the putative mediator of PPP3CC's effect on antidepressant response (P=0.03). Among innovative candidates, PPP3CC, involved in the regulation of immune system and synaptic plasticity, seems promising for further investigation.
Trial registration: ClinicalTrials.gov NCT00021528.