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Association of <emph type="ital">FKBP5</emph> Polymorphisms and Childhood Abuse With Risk of Posttraumatic Stress Disorder Symptoms in Adults
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CONTEXT: In addition to trauma exposure, other factors contribute to risk for development of posttraumatic stress disorder (PTSD) in adulthood. Both genetic and environmental factors are contributory, with child abuse providing significant risk liability. OBJECTIVE: To increase understanding of genetic and environmental risk factors as well as their interaction in the development of PTSD by gene x environment interactions of child abuse, level of non-child abuse trauma exposure, and genetic polymorphisms at the stress-related gene FKBP5. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study examining genetic and psychological risk factors in 900 nonpsychiatric clinic patients (762 included for all genotype studies) with significant levels of childhood abuse as well as non-child abuse trauma using a verbally presented survey combined with single-nucleotide polymorphism (SNP) genotyping. Participants were primarily urban, low-income, black (>95%) men and women seeking care in the general medical care and obstetrics-gynecology clinics of an urban public hospital in Atlanta, Georgia, between 2005 and 2007. MAIN OUTCOME MEASURES: Severity of adult PTSD symptomatology, measured with the modified PTSD Symptom Scale, non-child abuse (primarily adult) trauma exposure and child abuse measured using the traumatic events inventory and 8 SNPs spanning the FKBP5 locus. RESULTS: Level of child abuse and non-child abuse trauma each separately predicted level of adult PTSD symptomatology (mean [SD], PTSD Symptom Scale for no child abuse, 8.03 [10.48] vs > or =2 types of abuse, 20.93 [14.32]; and for no non-child abuse trauma, 3.58 [6.27] vs > or =4 types, 16.74 [12.90]; P < .001). Although FKBP5 SNPs did not directly predict PTSD symptom outcome or interact with level of non-child abuse trauma to predict PTSD symptom severity, 4 SNPs in the FKBP5 locus significantly interacted (rs9296158, rs3800373, rs1360780, and rs9470080; minimum P = .0004) with the severity of child abuse to predict level of adult PTSD symptoms after correcting for multiple testing. This gene x environment interaction remained significant when controlling for depression severity scores, age, sex, levels of non-child abuse trauma exposure, and genetic ancestry. This genetic interaction was also paralleled by FKBP5 genotype-dependent and PTSD-dependent effects on glucocorticoid receptor sensitivity, measured by the dexamethasone suppression test. CONCLUSIONS: Four SNPs of the FKBP5 gene interacted with severity of child abuse as a predictor of adult PTSD symptoms. There were no main effects of the SNPs on PTSD symptoms and no significant genetic interactions with level of non-child abuse trauma as predictor of adult PTSD symptoms, suggesting a potential gene-childhood environment interaction for adult PTSD.
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“Importantly, SNPs in the FKBP5 gene that are associated with higher FKBP5-mRNA induction upon cortisol release (rs1360780, rs9296158, rs3800373, and rs9470080) are also associated with increased PTSD symptom severity in those with high levels of child abuse (Binder et al, 2008).”
From Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond (2017) · cites this paper as Binder et al, 2008
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“FKBP5 single nucleotide polymorphisms have additionally been shown to interact with early trauma to predict both PTSD and major depression (36,37), possibly through involvement of allelespecific, environmentally dependent changes in methylation of specific cytosine-phosphate-guanine (CpG) sites (38).”
From Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation (2016) · cites this paper as [36]
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“As first shown by Binder et al. (385), specific single-nucleotide poly-morphisms (SNPs) of the FKBP5 gene interacting with ELS/CT predict the level of adult PTSD symptoms.”
From Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation (2019) · cites this paper as [385]
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“Interestingly, some alleles of these FKBP5-SNPs are associated with enhanced glucocorticoid sensitivity, whereas other alleles of these SNPs are associated with GR resistance in individuals with PTSD (Binder et al, 2008).”
From Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond (2017) · cites this paper as Binder et al, 2008
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“Moreover, these interaction effects remained significant even after controlling for potential confounds (i.e., depressive symptoms, age, sex, non-child abuse trauma, genetic ancestry).”
From Gene–environment interactions: early life stress and risk for depressive and anxiety disorders (2011) · cites this paper as Binder et al. 2008
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“FKBP5 interacted with reported childhood maltreatment to predict PTSD symptoms.”
From Gene–environment interactions: early life stress and risk for depressive and anxiety disorders (2011) · cites this paper as Binder et al. 2008
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“polymorphisms in both the GR and the GR-associated heat-shock protein FKBP5 have been shown to predict clinical response.48”
From Early life adversity and the epigenetic programming of hypothalamic-pituitary-adrenal function (2014) · cites this paper as [48]
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“Also, recently several single nucleotide polymorphisms of the FK506 binding protein 5 (FKBP5) were found to interact with childhood trauma in order to create PTSD susceptibility [195].”
From Oxidative Stress Implications in the Affective Disorders: Main Biomarkers, Animal Models Relevance, Genetic Perspectives, and Antioxidant Approaches (2016) · cites this paper as [195]
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“This study was the first to identify a correlation of FKBP51 gene variants with response to antidepressant treatment, and also with the reactivity of the HPA axis in the dexamethasone (DEX)-CRH test.”
From FKBP51 and FKBP52 in signaling and disease (2011) · cites this paper as [73]
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“Further, PTSD has long been associated with intrinsic [e.g., age and gender (48, 49)], environmental (e.g., exposure to trauma, rearing environment, degree of social support), and genetic factors (50–52).”
From Conditioned fear associated phenotypes as robust, translational indices of trauma-, stressor-, and anxiety-related behaviors (2014) · cites this paper as [51]
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“a functional variant in FKBP5, a gene encoding a co-chaperone of the glucocorticoid receptor, increases risk for PTSD following trauma 96 .”
From Post‐traumatic stress disorder: a state‐of‐the‐art review of evidence and challenges (2019) · cites this paper as [96]
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“with evidence that childhood trauma modifies the genetic risk for PTSD 96 .”
From Post‐traumatic stress disorder: a state‐of‐the‐art review of evidence and challenges (2019) · cites this paper as [96]
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Citations
Cites
Diagnostic and Statistical Manual of Mental Disorders
American Psychiatric Association (2013) · doi:10.1176/appi.books.9780890425596 · Cited by 116,369
Diagnostic and Statistical Manual of Mental Disorders
Williams, J. B. W., & First, M. B. (2013) · Oxford University Press eBooks · doi:10.1093/acrefore/9780199975839.013.104 · Cited by 109,845
An inventory for measuring depression
BECK, A. T. (1961) · Archives of General Psychiatry · doi:10.1001/archpsyc.1961.01710120031004 · Cited by 38,032
Haploview: analysis and visualization of LD and haplotype maps
Barrett, J. C., Fry, B., Maller, J., & Daly, M. J. (2004) · Bioinformatics · doi:10.1093/bioinformatics/bth457 · Cited by 14,563
Psychometric properties of the Beck Depression Inventory: Twenty-five years of evaluation
Beck, A. T., Steer, R. A., & Carbin, M. G. (1988) · Clinical Psychology Review · doi:10.1016/0272-7358(88)90050-5 · Cited by 11,696
Posttraumatic Stress Disorder in the National Comorbidity Survey
Kessler, R. C. (1995) · Archives of General Psychiatry · doi:10.1001/archpsyc.1995.03950240066012 · Cited by 10,379
Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene
Caspi, A., Sugden, K., Moffitt, T. E., Taylor, A., Craig, I. W., Harrington, H., McClay, J., Mill, J., Martin, J., Braithwaite, A., et al. (2003) · Science · doi:10.1126/science.1083968 · Cited by 8,120
The American Psychological Association
Langfeld, H. S. (1919) · Science · doi:10.1126/science.49.1254.51 · Cited by 7,453
Development and validation of a brief screening version of the Childhood Trauma Questionnaire
Bernstein, D. P., Stein, J. A., Newcomb, M. D., Walker, E., Pogge, D., Ahluvalia, T., Stokes, J., Handelsman, L., Medrano, M., Desmond, D., et al. (2003) · Child Abuse & Neglect · doi:10.1016/s0145-2134(02)00541-0 · Cited by 6,419
Role of genotype in the cycle of violence in maltreated children
Caspi, A., McClay, J., Moffitt, T. E., Mill, J., Martin, J., Craig, I. W., Taylor, A., & Poulton, R. (2002) · Science · doi:10.1126/science.1072290 · Cited by 4,842
Research works printed but not linked: 7
- [33]33. FKBP5 POLYMORPHISMS AND POSTTRAUMATIC STRESS DISORDER 1304 JAMA, March 19, 2008-Vol 299, No. 11 (Reprinted) ©2008 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 08/02/2023
- [39]39. Kendler KS, Kuhn JW, Vittum J, et al. The interac- tion of stressful life events and a serotonin transporter poly- morphisminthepredictionofepisodesofmajordepression. Arch Gen Psychiatry. 2005;62(5):529-535.
- [44]44. Yehuda R, Giller EL, Southwick SM, et al. Hypo- thalamic-pituitary-adrenal dysfunction in posttrau- matic stress disorder. Biol Psychiatry. 1991;30(10): 1031-1048.
- [54]54. Vermeer H, Hendriks-Stegeman BI, van der Burg B, et al. Glucocorticoid-induced increase in lympho- cytic FKBP51 messenger ribonucleic acid expression. J Clin Endocrinol Metab. 2003;88(1):277-284.
- [55]55. Denny WB, Valentine DL, Reynolds PD, et al. Squir- rel monkey immunophilin FKBP51 is a potent inhibi- tor of glucocorticoid receptor binding. Endocrinology. 2000;141(11):4107-4113.
- [82]82. Blalock H. Social Statistics. New York, NY: McGraw-Hill; 1972:406-407.
- [90]90. Schilling EA, Aseltine RH Jr, Gore S. Adverse child- hood experiences and mental health in young adults. BMC Public Health. 2007;7:30.
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How epigenetic inheritance fails to explain the Black-White health gap
Charney, E., Darity, W., & Hubbard, L. (2025) · Social Science & Medicine · doi:10.1016/j.socscimed.2025.117697 · Cited by 1
Jiang, W., Bronk, G., Lake, M. T., Hoffman, N., Zar, H. J., Breen, M. S., Stein, D. J., Koen, N., Ressler, K. J., & Klengel, T. (2026) · American Journal of Psychiatry · doi:10.1176/appi.ajp.20251098
Gene expression associated with PTSD in World Trade Center responders: An RNA sequencing study
Kuan, P.-F., Waszczuk, M. A., Kotov, R., Clouston, S., Yang, X., Singh, P. K., Glenn, S. T., Cortes Gomez, E., Wang, J., Bromet, E., et al. (2017) · Translational Psychiatry · doi:10.1038/s41398-017-0050-1 · Cited by 80
Metadata
- Authors
- Binder, E. B.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Binder, Elisabeth B.
- ORCID
- Binder, Elisabeth B.
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2008-03-19
- Volume
- 299
- Issue
- 11
- Pages
- 1291
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC2441757
- OpenAlex
- W2166401337
- Semantic Scholar
- ad909ca1aa67b7fa8a5e7cc745e773d2e0fba820
- Cited by
- 1,362
- References
- 95
- Citations by year
- 2026: 37 · 2025: 30 · 2024: 49 · 2023: 42 · 2022: 50 · 2021: 50 · 2020: 82 · 2019: 65 · 2018: 90 · 2017: 84 · 2016: 113 · 2015: 113 · 2014: 109 · 2013: 106 · 2012: 81
- FWCI
- 96.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- National Institutes of Health (UL1TR000454)
- National Institute of Mental Health (R01MH042088, P50MH058922, MH58922, MH 071537, MH069884, R01MH071537, MH42088, R56MH071537, K01MH069884)
- National Institute on Drug Abuse (DA015766, K02DA015766)
- National Center for Research Resources (M01RR000039)
- National Center for Advancing Translational Sciences
- Topics
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- post-traumatic stress disorder, childhood abuse, FKBP5, gene-environment interaction, single nucleotide polymorphisms, trauma exposure, PTSD symptom severity, genetic risk factors, stress-related genes, rs1360780
- MeSH terms
- Tacrolimus Binding Protein 5, Adolescent, Adult, Aged, Aged, 80 and over, Child, Child Abuse, Cross-Sectional Studies, Dexamethasone, Female, Humans, Hydrocortisone, Male, Middle Aged, Poverty, Receptors, Glucocorticoid, Regression Analysis, Risk Factors, Severity of Illness Index, Stress Disorders, Post-Traumatic, Urban Population, Polymorphism, Single Nucleotide, Tacrolimus Binding Proteins
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