TY - JOUR
T1 - Genetic markers for PTSD risk and resilience among survivors of the World Trade Center attacks
AU - Sarapas, Casey
AU - Cai, Guiqing
AU - Bierer, Linda M.
AU - Golier, Julia A.
AU - Galea, Sandro
AU - Ising, Marcus
AU - Rein, Theo
AU - Schmeidler, James
AU - Müller-Myhsok, Bertram
AU - Uhr, Manfred
AU - Holsboer, Florian
AU - Buxbaum, Joseph D.
AU - Yehuda, Rachel
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
KW - FKBP5 protein
KW - September 11 terrorist attacks
KW - Stress disorders
KW - childhood trauma
KW - cortisol
KW - gene expression
KW - genotype
KW - human
KW - post-traumatic
UR - http://www.scopus.com/inward/record.url?scp=79955125328&partnerID=8YFLogxK
U2 - 10.3233/DMA-2011-0764
DO - 10.3233/DMA-2011-0764
M3 - Article
AN - SCOPUS:79955125328
SN - 0278-0240
VL - 30
SP - 101
EP - 110
JO - Disease Markers
JF - Disease Markers
IS - 2-3
ER -