Major depressive disorder (MDD) is a common, debilitating, phenotypically heterogeneous disorder with heritability ranges from 30% to 50%. Compared to other psychiatric disorders, its high prevalence, moderate heritability, and strong polygenicity have posed major challenges for gene-mapping in MDD. Studies of common genetic variation in MDD, driven by large international collaborations such as the Psychiatric Genomics Consortium, have confirmed the highly polygenic nature of the disorder and implicated over 100 genetic risk loci to date. Rare copy number variants associated with MDD risk were also recently identified. The goal of this review is to present a broad picture of our current understanding of the epidemiology, genetic epidemiology, molecular genetics, and gene–environment interplay in MDD. Insights into the impact of genetic factors on the aetiology of this complex disorder hold great promise for improving clinical care.

Background: Parenting dimensions are associated with depressive symptoms in adolescents. We investigated the role of perceived parenting dimensions and gene-environment interactions between these perceived parenting dimensions and five well-known variable number of tandem repeats (VNTRs): 5-HTTLPR, STin2, DAT1, DRD4, and MAO-A, in depressive symptoms.Methods: From a non-clinical sample of 1111 Belgian adolescents (mean age: 13.79 years, SD = .94; 51% boys), 1103 adolescents consented for genetic research. Five VNTRs were analyzed using DNA from saliva samples. Perceived parenting dimensions (i.e., support, proactive control, psychological control, punishment, and harsh punishment) were examined using self-report scales completed by adolescents and their parents. Depressive symptoms were investigated using the CES-D self-report scale. Statistical analyses were performed in R using linear regression.Results: Parental support, as perceived by the adolescent, was negatively associated with depressive symptoms (CES-D) and psychological control was positively associated with these symptoms. The only interaction effect withstanding correction for multiple testing was observed for 5-HTTLPR and the difference in proactive control as perceived by adolescents in comparison to parents. Short-allele carriers showed more depressive symptoms when there was a higher discrepancy in proactive control as perceived by adolescents versus parents.Conclusions: Our results suggest that perceived parenting dimensions are associated with depressive symptoms, as measured by the CES-D. We only found modest evidence for 5-HTTLPR as a moderator in the association between the difference in perception of proactive control (adolescents vs. parents) and depressive symptoms.