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Replication and Extension

Guilherme Polanczyk, MD, PhD; Avshalom Caspi, PhD; Benjamin Williams, BSc; Thomas S. Price, PhD; Andrea Danese, MD; Karen Sugden, PhD; Rudolf Uher, MD, PhD; Richie Poulton, PhD; Terrie E. Moffitt, PhD

Arch Gen Psychiatry. 2009;66(9):978-985.

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.

Author Affiliations: Departments of Psychology and Neuroscience and Psychiatry and Behavioral Sciences and Institute for Genome Sciences and Policy, Duke University, Durham, North Carolina (Drs Polanczyk, Caspi, Sugden, and Moffitt and Mr Williams); Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, England (Drs Polanczyk, Caspi, Price, Danese, Sugden, Uher, and Moffitt and Mr Williams); Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil (Dr Polanczyk); and Dunedin Multidisciplinary Health and Development Research Unit, University of Otago, Dunedin, New Zealand (Dr Poulton).

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