A Preliminary Study of Genetic Variation in the Dopaminergic and Serotonergic Systems and Genome-Wide Additive Genetic Effects on Depression Severity and Treatment Response

Major depression is a heritable disorder that is commonly treated with selective serotonin reuptake inhibitors. However, no study has quantified the overlap in genetic effects between pretreatment depression severity and treatment response and the extent to which genetic effects could be attributed to variation in the dopaminergic and serotonergic systems (DA/5-HT). Data (N=1618) from the clinician-rated Hamilton Rating Scale of Depression and the clinician-rated Quick Inventory of Depressive Symptomatology were obtained from participants of European ancestry in the Sequenced Treatment Alternatives to Relieve Depression clinical trial. Genetic variants explained 31%–64% of the variance across assessments of pretreatment depression severity and treatment response. However, effects from the DA/5-HT systems genes were negligible. There was also limited evidence for genetic overlap for pretreatment depression severity and treatment response. Despite the clear genetic contributions to these depression phenotypes, different genetic factors may contribute to depression severity and treatment response.