title: FKBP5 polymorphisms, childhood abuse, and PTSD symptoms: Results from the National Health and Resilience in Veterans Study.
abstract: Polymorphisms in the FK506 Binding Protein 5 (FKBP5) gene may interact with childhood abuse to increase risk of developing posttraumatic stress disorder (PTSD) symptoms. The objective of this study was to examine the relationship of four previously identified FKBP5 putative risk SNPs (rs9296158, rs3800373, rs1360780, rs947008), childhood abuse, and lifetime PTSD symptoms, including contemporary phenotypic models of PTSD symptoms, in two nationally representative samples of European-American (EA) U.S. military veterans. The main sample included 1585 EA veterans who participated in the National Health and Resilience in Veterans Study (NHRVS), and the replication sample included 577 EA veterans who participated in a second baseline cohort survey of the NHRVS. Outcome variables were lifetime PTSD symptom severity and a 4-factor phenotypic model of PTSD symptoms that included re-experiencing, avoidance, emotional numbing/negative cognitions and mood, and hyperarousal/alterations in arousal and reactivity symptoms. Results revealed that the four FKBP5 SNPs were associated with PTSD symptom severity in both samples (p values ranged from 0.001 to 0.012). Further, SNP rs9470080 in the main sample, and all four SNPs in the replication sample interacted with childhood abuse to predict PTSD severity (p values ranged from 0.002 to 0.006). In both samples, all four FKBP5 SNPs predicted hyperarousal/alterations in arousal and reactivity (p values ranged from<0.001 to 0.002). Results of this study suggest that FKBP5 polymorphisms, directly and interactively with childhood abuse, predict severity of lifetime PTSD symptoms, most notably hyperarousal symptoms, in two nationally representative samples of EA veterans. They further indicate that FKBP5 polymorphisms and childhood abuse may contribute to vulnerability for PTSD symptoms and may be most strongly associated with trauma-related hyperarousal symptoms that comprise this phenotype.
authors.affiliation: U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, VA Connecticut Healthcare System, West Haven, CT, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA. Electronic address: laura.watkins@yale.edu.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Watkins
authors.affiliation: Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
authors.forename: Shizhong
authors.initials: S
authors.lastname: Han
authors.affiliation: U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, VA Connecticut Healthcare System, West Haven, CT, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Ilan
authors.initials: I
authors.lastname: Harpaz-Rotem
authors.affiliation: Department of Clinical Health Psychology, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Natalie P
authors.initials: NP
authors.lastname: Mota
authors.affiliation: U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, VA Connecticut Healthcare System, West Haven, CT, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Southwick
authors.affiliation: U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, VA Connecticut Healthcare System, West Haven, CT, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Krystal
authors.affiliation: U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, VA Connecticut Healthcare System, West Haven, CT, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Gelernter
authors.affiliation: U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, VA Connecticut Healthcare System, West Haven, CT, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Pietrzak
mesh_terms: D000328:Adult; D000483:Alleles; D002648:Child; D002649:Child Abuse / Q000523:psychology; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D015810:Linkage Disequilibrium; D008297:Male; D010913:Pituitary-Adrenal System / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D013313:Stress Disorders, Post-Traumatic / Q000235:genetics* / Q000523:psychology; D019966:Substance-Related Disorders / Q000235:genetics; D022021:Tacrolimus Binding Proteins / Q000235:genetics* / Q000378:metabolism; D014728:Veterans / Q000523:psychology; D000099159:Tacrolimus Binding Protein 5
chemical_list: D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5
keywords: Childhood abuse; FKBP5; Gene environment interaction; HPA axis; Posttraumatic stress disorder