Moderation of Adult Depression by a Polymorphism in the FKBP5 Gene and Childhood Physical Abuse in the General Population
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Childhood maltreatment and depressive disorders have both been associated with a dysregulation of the hypothalamic-pituitary-adrenal axis. The FKBP5 gene codes for a co-chaperone regulating the glucocorticoid-receptor sensitivity. Previous evidence suggests that subjects carrying the TT genotype of the FKBP5 gene single-nucleotide polymorphism (SNP) rs1360780 have an increased susceptibility to adverse effects of experimental stress. We therefore tested the hypothesis of an interaction of childhood abuse with rs1360780 in predicting adult depression. In all, 2157 Caucasian subjects from the Study of Health in Pomerania (German general population) completed the Beck Depression Inventory (BDI-II) and Childhood Trauma Questionnaire. The DSM-IV diagnosis of major depressive disorder (MDD) was assessed by interview. Genotypes of rs1360780 were taken from the Affymetrix Human SNP Array 6.0. Significant interaction (p=0.006) of physical abuse with the TT genotype of rs1360780 was found increasing the BDI-II score to 17.4 (95% confidence interval (CI)=12.0-22.9) compared with 10.0 (8.2-11.7) in exposed CC/CT carriers. Likewise, the adjusted odds ratio for MDD in exposed TT carriers was 8.2 (95% CI=1.9-35.0) compared with 1.3 (0.8-2.3) in exposed subjects with CC/CT genotypes. Relative excess risk due to interaction (RERI) analyses confirmed a significant additive interaction effect (RERI=6.8; 95% CI=0.64-33.7; p<0.05). In explorative analyses, the most severe degree of sexual and emotional abuse also yielded significant interaction effects (p<0.05). This study revealed interactions between physical abuse and rs1360780 of the FKBP5 gene, confirming its role in the individual susceptibility to depression. Given the large effect sizes, rs1360780 could be included into prediction models for depression in individuals exposed to childhood abuse.
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The interaction between rs1360780 and childhood abuse has been associated with psychiatric conditions later in life, including MDD.
“Further studies have associated this interaction between rs1360780 and childhood abuse with psychiatric conditions later in life, including MDD, 70 , 71 highlighting its clinical relevance.”
From Epigenetics and depression (2019) · cites this paper as [70]
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- Authors
- Appel, K., Schwahn, C., Mahler, J., Schulz, A., Spitzer, C., Fenske, K., Stender, J., Barnow, S., John, U., Teumer, A., Biffar, R., Nauck, M., Völzke, H., Freyberger, H. J., & Grabe, H. J.
- Affiliations
- Universität Greifswald (DE)
- Universität Hamburg (DE)
- Heidelberg University (DE)
- Universitätsmedizin Greifswald (DE)
- Corresponding author
- Appel, Katja
- ORCID
- Venue
- Neuropsychopharmacology
- Published
- 2011-06-08
- Volume
- 36
- Issue
- 10
- Pages
- 1982-1991
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC3158316
- OpenAlex
- W1977244886
- Cited by
- 234
- References
- 8
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 9 · 2023: 11 · 2022: 4 · 2021: 11 · 2020: 15 · 2019: 21 · 2018: 19 · 2017: 19 · 2016: 25 · 2015: 29 · 2014: 23 · 2013: 18 · 2012: 18
- FWCI
- 21.41
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (Gr1912/5‐1, 01ZZ0403, DFG: GR 1912/5‐1, 01ZZ9603, 03ZIK012, 01ZZ0103)
- Bundesministerium für Bildung und Forschung (01ZZ9603, 01ZZ0103, and 01ZZ0403, 03ZIK012, 01ZZ0403, and 01ZZ0403, 01ZZ0103, 01ZZ9603)
- Siemens
- Universität Greifswald
- Ministry of Cultural Affairs
- 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
- adult depression, rs1360780, child physical abuse, child abuse, major depressive disorder, gene-environment interaction, hypothalamic-pituitary-adrenal axis, glucocorticoid receptor, genetic susceptibility, sexual abuse, emotional abuse, depression prediction
- MeSH terms
- Tacrolimus Binding Protein 5, Adult, Aged, Major Depressive Disorder, Depressive Disorder, Major, Female, Humans, Male, Middle Aged, Models, Genetic, Population Surveillance, Predictive Value of Tests, Surveys and Questionnaires, Registries, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Tacrolimus Binding Proteins, Adult Survivors of Child Abuse, Young Adult
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