title: Genetic markers for PTSD risk and resilience among survivors of the World Trade Center attacks.
abstract: We have previously reported the differential expression of 17 probe sets in survivors of the 9/11 attacks with current posttraumatic stress disorder (PTSD) compared to similarly exposed survivors with no lifetime PTSD. The current study presents an expanded analysis of these subjects, including genotype at FKBP5, a modulator of glucocorticoid receptor (GR) sensitivity. It includes data from additional subjects who developed PTSD following 9/11 but then recovered, distinguishing expression profiles associated with risk for developing PTSD, resilience, and symptom recovery. 40 Caucasians (20 with and 20 without PTSD, matched for exposure, age, and gender) were selected from a population-representative sample of persons exposed to the 9/11 attacks from which longitudinal data had been collected in four previous waves. Whole blood gene expression and cortisol levels were obtained and genome-wide gene expression was analyzed. 25 probe sets were differentially expressed in PTSD. Identified genes were generally involved in hypothalamic-pituitary-adrenal axis, signal transduction, or in brain and immune cell function. STAT5B, a direct inhibitor of GR, and nuclear factor I/A, both showed reduced expression in PTSD. Comparison of lifetime versus current PTSD identified overlapping genes with altered expression suggesting enduring markers, while some markers present only in current PTSD may reflect state measures. As a follow-up, direct comparisons of expression in current PTSD, lifetime-only PTSD, and control groups identified FKBP5 and MHC Class II as state markers, and also identified several trait markers. An analysis of indirect effects revealed that homozygosity for any of 4 PTSD risk-related polymorphisms at FKBP5 predicted FKBP5 expression, which mediated indirect effects of genotype on plasma cortisol and PTSD severity.
authors.affiliation: Department of Psychology, University of Illinois at Chicago, USA.
authors.forename: Casey
authors.initials: C
authors.lastname: Sarapas
authors.forename: Guiqing
authors.initials: G
authors.lastname: Cai
authors.forename: Linda M
authors.initials: LM
authors.lastname: Bierer
authors.forename: Julia A
authors.initials: JA
authors.lastname: Golier
authors.forename: Sandro
authors.initials: S
authors.lastname: Galea
authors.forename: Marcus
authors.initials: M
authors.lastname: Ising
authors.forename: Theo
authors.initials: T
authors.lastname: Rein
authors.forename: James
authors.initials: J
authors.lastname: Schmeidler
authors.forename: Bertram
authors.initials: B
authors.lastname: Müller-Myhsok
authors.forename: Manfred
authors.initials: M
authors.lastname: Uhr
authors.forename: Florian
authors.initials: F
authors.lastname: Holsboer
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Buxbaum
authors.forename: Rachel
authors.initials: R
authors.lastname: Yehuda
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D020869:Gene Expression Profiling; D005802:Genes, MHC Class II; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D014176:Protein Biosynthesis; D055500:Resilience, Psychological; D012307:Risk Factors; D047851:September 11 Terrorist Attacks / Q000523:psychology*; D012720:Severity of Illness Index; D013313:Stress Disorders, Post-Traumatic / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology; D017741:Survivors / Q000523:psychology*; D022021:Tacrolimus Binding Proteins / Q000235:genetics* / Q000378:metabolism; D000099159:Tacrolimus Binding Protein 5
chemical_list: D005819:Genetic Markers; D006854:Hydrocortisone; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5