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

Arch Gen Psychiatry. 2009 Sep;66(9):978-85. doi: 10.1001/archgenpsychiatry.2009.114.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Child
  • Child Abuse / psychology
  • Child Abuse / statistics & numerical data*
  • Child Abuse, Sexual / psychology
  • Child Abuse, Sexual / statistics & numerical data
  • Child, Preschool
  • Corticotropin-Releasing Hormone / genetics
  • Depressive Disorder / diagnosis
  • Depressive Disorder / genetics*
  • Depressive Disorder / prevention & control
  • Female
  • Genetic Variation / genetics*
  • Genotype
  • Haplotypes / genetics
  • Humans
  • Life Change Events*
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Polymorphism, Single Nucleotide
  • Psychiatric Status Rating Scales
  • Receptors, Corticotropin-Releasing Hormone / genetics*
  • Surveys and Questionnaires

Substances

  • Receptors, Corticotropin-Releasing Hormone
  • CRF receptor type 1
  • Corticotropin-Releasing Hormone