Protective effect of CRHR1 gene variants on the development of adult depression following childhood maltreatment: Replication and extension

Context: A previous study reported a gene x environment interaction in which a haplotype in the corticotropin-releasing hormone receptor 1 gene (CRHR1) was associated with protection against adult depressive symptoms in individuals who were maltreated as children (as assessed by the Childhood Trauma Questionnaire [CTQ]). Objective: To replicate the interaction between childhood maltreatment and a TAT haplotype formed by rs7209436, rs110402, and rs242924 in CRHR1, predicting adult depression. Design: Two prospective longitudinal cohort studies. Setting: England and New Zealand. Participants: Participants in the first sample were women in the E-Risk Study (N=1116), followed up to age 40 years with 96% retention. Participants in the second sample were men and women in the Dunedin Study (N=1037), followed up to age 32 years with 96% retention. Main Outcome Measure: Research diagnoses of past-year and recurrent major depressive disorder. Results: In the E-Risk Study, the TAT haplotype was associated with a significant protective effect. In this effect, women who reported childhood maltreatment on the CTQ were protected against depression. In the Dunedin Study, which used a different type of measure of maltreatment, this finding was not replicated. Conclusions: A haplotype in CRHR1 has been suggested to exert a protective effect against adult depression among research participants who reported maltreatment on the CTQ, a measure that elicits emotional memories. This suggests the hypothesis that CRHR1's protective effect may relate to its function in the consolidation of memories of emotionally arousing experiences.