Protective Effect of CRHR1 Gene Variants on the Development of Adult Depression Following Childhood Maltreatment: Replication and Extension
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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.
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Polanczyk et al. concluded that the gene-environment effect was supported but specific to depression-relevant emotional memories assessed with the CTQ.
“Polanczyk et al. concluded that the GxE effect was supported, but with the effect specific to depression-relevant emotional memories assessed with the CTQ.”
From Gene–environment interactions: early life stress and risk for depressive and anxiety disorders (2011) · cites this paper as Polanczyk et al. (2009)
Polanczyk et al.'s Dunedin cohort did not support the expected gene-environment interaction.
“However, results from the Dunedin cohort, comprised of both men and women, did not support the expected GxE interaction.”
From Gene–environment interactions: early life stress and risk for depressive and anxiety disorders (2011) · cites this paper as Polanczyk et al. (2009)
Polanczyk et al. (2009) replicated in the E-Risk cohort the interaction of retrospective childhood maltreatment with the TAT haplotype in predicting depression diagnoses.
“Findings from their E-Risk cohort, a large study of women, replicated the interaction of retrospective reports of childhood maltreatment with the TAT haplotype (rs7209436, rs110402, and rs242924) in predicting depression diagnoses.”
From Gene–environment interactions: early life stress and risk for depressive and anxiety disorders (2011) · cites this paper as Polanczyk et al. (2009)
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“…fact that children who had experienced 3 or 4 types of maltreatment had levels of neuroticism similar to those of the nonmaltreated group (Figure 1b) is reminiscent of the protective effect of the TAT haplotype on depression seen in previous research (Bradley et al., 2008; Polanczyk et al., 2009).”
BackgroundMethodResultInfluentialGene-environment interactions between CRHR1 variants and physical assault in suicide attempts
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Em busca das origens desenvolvimentais dos transtornos mentais
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- Authors
- Polanczyk, G., Caspi, A., Williams, B., Price, T. S., Danese, A., Sugden, K., Uher, R., Poulton, R., & Moffitt, T. E.
- Affiliations
- Duke University (US)
- ORCID
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2009-09-01
- Volume
- 66
- Issue
- 9
- Pages
- 978
- ISSN
- 0003-990X (ISSN-L)
- PMC
- PMC3750953
- OpenAlex
- W2161054449
- Cited by
- 285
- References
- 32
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 3 · 2023: 2 · 2022: 6 · 2021: 9 · 2020: 12 · 2019: 13 · 2018: 13 · 2017: 12 · 2016: 32 · 2015: 31 · 2014: 29 · 2013: 31 · 2012: 28
- FWCI
- 30.48
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- National Institute of Mental Health (MH-49414, MH-077874, MH 45070, R01MH049414, R01MH077874, R01MH045070)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- CRHR1, corticotropin-releasing hormone receptor 1, child abuse, adult depression, gene-environment interaction, major depressive disorder, childhood trauma, memory consolidation, emotional memory, protective genetic effect, replication
- MeSH terms
- CRF Receptor, Type 1, Adult, Child, Child Abuse, Child Abuse, Sexual, Child, Preschool, Corticotropin-Releasing Hormone, Depressive Disorder, Female, Genotype, Haplotypes, Humans, Life Change Events, Male, Middle Aged, Polymorphism, Genetic, Psychiatric Status Rating Scales, Surveys and Questionnaires, Genetic Variation, Receptors, Corticotropin-Releasing Hormone, Polymorphism, Single Nucleotide
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