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Interaction of FKBP5, a Stress-Related Gene, with Childhood Trauma Increases the Risk for Attempting Suicide
Open accessAbstract
Childhood trauma is associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation and is a known risk factor for suicidal behavior. In this study we sought to determine whether the impact of childhood trauma on suicide risk might be modified by FKBP5, an HPA-axis regulating gene. Sixteen FKBP5 haplotype-tagging single nucleotide polymorphisms (SNPs) were genotyped in a sample of African Americans: 398 treatment-seeking patients with substance dependence (90% men; 120 suicide attempters) and 432 nonsubstance-dependent individuals (40% men; 21 suicide attempters). In all, 474 participants (112 suicide attempters) also completed the Childhood Trauma Questionnaire (CTQ). Primary haplotype analyses were conducted with the four SNPs implicated in earlier studies: rs3800373, rs9296158, rs1360780, and rs9470080. We found that childhood trauma was associated with suicide attempt (P<0.0001). Although there was no main effect of the two major yin yang haplotypes in the four SNP haplotype blocks, there was a haplotype influence on suicide risk (p=0.006) only in individuals exposed to high levels of childhood trauma. In this group, 51% with two copies of the risk haplotype, 36% with one copy, and 20% with no copies had attempted suicide. The total logistic regression model accounted for 13% of the variance in attempted suicide. Analyses of the 16 SNPs showed significant main effects on suicide attempt of rs3777747, rs4713902, and rs9470080 and interactive effects of rs3800373, rs9296158, and rs1360780 with CTQ score on suicide attempt. These data suggest that childhood trauma and variants of the FKBP5 gene may interact to increase the risk for attempting suicide.
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“Further clinical studies confirm minor alleles of FKBP5 being particularly sensitive and interact with ELS/CT to increase aggressive behavior (387), suicide attempts (388), and depression (389).”
From Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation (2019) · cites this paper as [388]
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“Glucocorticoid receptors are subject to genetic effects via chaperone proteins like SKA1 and FKBP5 (58, 148, 149), as well as epigenetic changes (i.e., methylation) observed in response to maternal deprivation in rats (150) and in suicide decedents with a history of childhood adversity (60).”
From A brain-centric model of suicidal behavior (2020) · cites this paper as [148]
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Allele-specific FKBP5 DNA demethylation mediates gene–childhood trauma interactions
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Metadata
- Authors
- Roy, A., Gorodetsky, E., Yuan, Q., Goldman, D., & Enoch, M.-A.
- Affiliations
- VA New Jersey Health Care System (US)
- National Institutes of Health (US)
- Corresponding author
- Roy, Alec
- Venue
- Neuropsychopharmacology
- Published
- 2010-01-20
- Volume
- 35
- Issue
- 8
- Pages
- 1674-1683
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC2962602
- OpenAlex
- W2043313558
- Cited by
- 282
- References
- 73
- Citations by year
- 2025: 8 · 2024: 1 · 2023: 12 · 2022: 7 · 2021: 22 · 2020: 15 · 2019: 17 · 2018: 34 · 2017: 18 · 2016: 28 · 2015: 30 · 2014: 26 · 2013: 21 · 2012: 18
- FWCI
- 22.42
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (Z99‐AA999999)
- National Institute on Alcohol Abuse and Alcoholism (Z01AA000301, ZIAAA000306)
- National Institute on Drug Abuse (R01DA010336)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- FKBP5, childhood trauma, suicide attempts, gene-environment interaction, HPA axis dysregulation, single nucleotide polymorphisms, haplotypes, substance dependence, African Americans, stress-related genes
- MeSH terms
- Tacrolimus Binding Protein 5, Adult, Black or African American, Female, Gene Frequency, Genotype, Humans, Male, Middle Aged, New Jersey, Surveys and Questionnaires, Risk Factors, Suicide, Attempted, Linkage Disequilibrium, Computational Biology, Substance-Related Disorders, Polymorphism, Single Nucleotide, Tacrolimus Binding Proteins, Adult Survivors of Child Abuse, Young Adult
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