Sensitizing effect of early adversity on depressive reactions to later proximal stress: Moderation by 5-HTTLPR and CRHR1 in a 20-year longitudinal study

摘要

Previous research supports gene-environment interactions for polymorphisms in corticotrophin hormone receptor (CRHR1) and the serotonin transporter (5-HTTLPR) genes in predicting depression, but has rarely considered genetic influences on stress sensitization processes, whereby early adversities (EA) increase depressive reactivity to proximal stressors later in life. The current study tested a gene-environment-environment interaction (G × E × E; specifically gene-EA-proximal stress interaction) model of depression in a 20-year longitudinal study. Participants were assessed prospectively for EA up to age 5 and recent chronic stress and depressive symptoms at age 20 and genotyped for CRHR1 SNP rs110402 and 5-HTTLPR. EA predicted stronger associations between recent chronic stress and depression, and the effect was moderated by genes. CRHR1 A alleles and 5-HTTLPR short alleles were associated with greater stress sensitization (i.e., greater depressive reactivity to chronic stress for those also exposed to high levels of EA). Results are consistent with the notion that EA exposure results in neurobiological and cognitive-emotional consequences (e.g., altered hypothalamic-pituitary- adrenal [HPA] axis functioning) leading to emotional distress in the face of recent stressors among those with certain genetic characteristics, although further research is needed to explore explanatory mechanisms.