Affiliations: Department 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 | Departments 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 | Department of Epidemiology, Columbia Mailman School of
Public Health, New York, NY, USA
Abstract: 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.
