Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults

Elisabeth B. Binder, Rebekah G. Bradley, Wei Liu, Michael P. Epstein, Todd C. Deveau, Kristina B. Mercer, Yilang Tang, Charles F. Gillespie, Christine M. Heim, Charles Nemeroff, Ann C. Schwartz, Joseph F. Cubells, Kerry J. Ressler

Research output: Contribution to journalArticle

864 Citations (Scopus)

Abstract

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 ≥2 types of abuse, 20.93 [14.32]; and for no non-child abuse trauma, 3.58 [6.27] vs ≥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.

Original languageEnglish
Pages (from-to)1291-1305
Number of pages15
JournalJAMA - Journal of the American Medical Association
Volume299
Issue number11
DOIs
StatePublished - Mar 19 2008
Externally publishedYes

Fingerprint

Post-Traumatic Stress Disorders
Child Abuse
Single Nucleotide Polymorphism
Wounds and Injuries
Gene-Environment Interaction
Genotype
Public Hospitals
Urban Hospitals
Glucocorticoid Receptors
Genetic Polymorphisms
Gynecology
Dexamethasone
Genes
Obstetrics
Cross-Sectional Studies
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. / Binder, Elisabeth B.; Bradley, Rebekah G.; Liu, Wei; Epstein, Michael P.; Deveau, Todd C.; Mercer, Kristina B.; Tang, Yilang; Gillespie, Charles F.; Heim, Christine M.; Nemeroff, Charles; Schwartz, Ann C.; Cubells, Joseph F.; Ressler, Kerry J.

In: JAMA - Journal of the American Medical Association, Vol. 299, No. 11, 19.03.2008, p. 1291-1305.

Research output: Contribution to journalArticle

Binder, EB, Bradley, RG, Liu, W, Epstein, MP, Deveau, TC, Mercer, KB, Tang, Y, Gillespie, CF, Heim, CM, Nemeroff, C, Schwartz, AC, Cubells, JF & Ressler, KJ 2008, 'Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults', JAMA - Journal of the American Medical Association, vol. 299, no. 11, pp. 1291-1305. https://doi.org/10.1001/jama.299.11.1291
Binder, Elisabeth B. ; Bradley, Rebekah G. ; Liu, Wei ; Epstein, Michael P. ; Deveau, Todd C. ; Mercer, Kristina B. ; Tang, Yilang ; Gillespie, Charles F. ; Heim, Christine M. ; Nemeroff, Charles ; Schwartz, Ann C. ; Cubells, Joseph F. ; Ressler, Kerry J. / Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. In: JAMA - Journal of the American Medical Association. 2008 ; Vol. 299, No. 11. pp. 1291-1305.
@article{c1588f6fa7ae4a19abbe8801a1ed41ce,
title = "Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults",
abstract = "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 ≥2 types of abuse, 20.93 [14.32]; and for no non-child abuse trauma, 3.58 [6.27] vs ≥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.",
author = "Binder, {Elisabeth B.} and Bradley, {Rebekah G.} and Wei Liu and Epstein, {Michael P.} and Deveau, {Todd C.} and Mercer, {Kristina B.} and Yilang Tang and Gillespie, {Charles F.} and Heim, {Christine M.} and Charles Nemeroff and Schwartz, {Ann C.} and Cubells, {Joseph F.} and Ressler, {Kerry J.}",
year = "2008",
month = "3",
day = "19",
doi = "10.1001/jama.299.11.1291",
language = "English",
volume = "299",
pages = "1291--1305",
journal = "JAMA - Journal of the American Medical Association",
issn = "0002-9955",
publisher = "American Medical Association",
number = "11",

}

TY - JOUR

T1 - Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults

AU - Binder, Elisabeth B.

AU - Bradley, Rebekah G.

AU - Liu, Wei

AU - Epstein, Michael P.

AU - Deveau, Todd C.

AU - Mercer, Kristina B.

AU - Tang, Yilang

AU - Gillespie, Charles F.

AU - Heim, Christine M.

AU - Nemeroff, Charles

AU - Schwartz, Ann C.

AU - Cubells, Joseph F.

AU - Ressler, Kerry J.

PY - 2008/3/19

Y1 - 2008/3/19

N2 - 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 ≥2 types of abuse, 20.93 [14.32]; and for no non-child abuse trauma, 3.58 [6.27] vs ≥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.

AB - 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 ≥2 types of abuse, 20.93 [14.32]; and for no non-child abuse trauma, 3.58 [6.27] vs ≥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.

UR - http://www.scopus.com/inward/record.url?scp=40949142290&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=40949142290&partnerID=8YFLogxK

U2 - 10.1001/jama.299.11.1291

DO - 10.1001/jama.299.11.1291

M3 - Article

C2 - 18349090

AN - SCOPUS:40949142290

VL - 299

SP - 1291

EP - 1305

JO - JAMA - Journal of the American Medical Association

JF - JAMA - Journal of the American Medical Association

SN - 0002-9955

IS - 11

ER -