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Disease Markers
Volume 30 (2011), Issue 2-3, Pages 101-110
http://dx.doi.org/10.3233/DMA-2011-0764

Genetic Markers for PTSD Risk and Resilience Among Survivors of the World Trade Center Attacks

Casey Sarapas,1 Guiqing Cai,2 Linda M. Bierer,3 Julia A. Golier,3 Sandro Galea,4 Marcus Ising,5 Theo Rein,5 James Schmeidler,3 Bertram Müller-Myhsok,5 Manfred Uhr,5 Florian Holsboer,5 Joseph D. Buxbaum,2 and Rachel Yehuda3

1Department of Psychology, University of Illinois at Chicago, Chicago, IL, USA
2Laboratory of Molecular Neuropsychiatry, Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA
3Traumatic Stress Studies Division, Mount Sinai School of Medicine and James J. Peters Veterans Affairs Medical Center, Bronx, NY, USA
4Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA
5Max Planck Institute for Psychiatry, Munich, Germany

Received 14 April 2011; Accepted 14 April 2011

Copyright © 2011 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.