Individual and Combined Effect of / Gene Variants and Adverse Childhood Experiences on the Severity of Major Depressive Disorder.

BACKGROUND

Major depressive disorder (MDD) is a mood disorder with a high prevalence worldwide that causes disability and, in some cases, suicide. Although environmental factors play a crucial role in this disease, other biological factors may predispose individuals to MDD. Genetic and environmental factors influence mental disorders; therefore, a potential combined effect of / gene variants may be a target for the study of susceptibility to MDD. This study aimed to evaluate the effects of and gene variants when combined with adverse childhood experiences (ACEs) on the susceptibility and severity of symptoms in MDD.

METHODS

A case-control study was performed, including 345 individuals, 175 MDD cases and 170 controls. Genotyping was performed using real-time PCR with hydrolysis probes. The analysis of the and gene variants of and , respectively, was performed either alone or in combination with ACEs on the severity of depression, as determined through specific questionnaires, including DSM-IV diagnostic criteria for MDD.

RESULTS

According to individual effects, the presence of ACEs, as well as the allele G of the rs1465107 of , is associated with a higher severity of depression, more significantly in females. Furthermore, the allele G of was associated with the severity of depression, even after being adjusted by gene variants and ACEs (IRR = 1.67, = 0.01). In males, the allele G of was shown to interact with SNP with ACEs (IRR = 1.70, < 0.001). According to combined effect analyses, the severity of depression was associated with ACEs when combined with either allele of or allele of , whereas SNP risk association was influenced by gender.

CONCLUSIONS

The severity of depression is related to either individual or combined effects of temperamental traits and genetic susceptibility of specific genes such as and .