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Disease Markers
Volume 30, Issue 2-3, Pages 67-76

The Role of Genes in Defining a Molecular Biology of PTSD

Rachel Yehuda,1 Karestan C. Koenen,2 Sandro Galea,3 and Janine D. Flory1

1Department of Psychiatry, James J. Peters Veterans Affairs Medical Center, Bronx, New York, USA and Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA
2Departments of Society, Human Development and Health and Epidemiology, Harvard School of Public Health, Boston, MA, USA and the Harvard Center on the Developing Child, Cambridge, MA, USA
3Department of Epidemiology, Columbia Mailman School of Public Health, New York, NY, USA

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.


Because environmental exposure to trauma is the sine qua non for the development of Post Traumatic Stress Disorder (PTSD), the recent focus on genetic studies has been noteworthy. The main catalyst for such studies is the observation from epidemiological studies that not all trauma survivors develop this disorder. Furthermore, neuroendocrine findings suggest pre-existing hormonal alterations that confer risk for PTSD. This paper presents the rationale for examining genetic factors in PTSD and trauma exposure, but suggests that studies of genotype may only present a limited picture of the molecular biology of this disorder. We describe the type of information that can be obtained from candidate gene and genomic studies that incorporate environmental factors in the design (i.e., gene – environment interaction and gene-environment correlation studies) and studies that capitalize on the idea that environment modifies gene expression, via epigenetic or other molecular mechanisms. The examination of epigenetic mechanisms in tandem with gene expression will help refine models that explain how PTSD risk, pathophysiology, and recovery is mediated by the environment. Since inherited genetic variation may also influence the extent of epigenetic or gene expression changes resulting from the environment, such studies should optimally be followed up by studies of genotype.