Biological markers and diagnostic accuracy in the genetics of posttraumatic stress disorder

Family and twin studies suggest a substantial genetic contribution to the etiology of posttraumatic stress disorder (PTSD). Identification of the nature of this genetic contribution should enhance understanding of the pathophysiology of PTSD and suggest improved therapeutic strategies for its treatment. However, a broadly defined phenotype, specific requirement for an environmental exposure and high frequency of comorbid psychiatric illness all complicate genetic studies of PTSD. It is likely that genetic heterogeneity, incomplete penetrance, pleiotropy and the involvement of more than one gene all constitute formidable obstacles to the genetic analysis of PTSD. One way to circumvent these problems is to perform genetic analysis of traits associated with PTSD, rather than PTSD itself, an approach that has been fruitful for other diseases with complex modes of inheritance. Hypothalamic-pituitary-adrenal axis hypofunction, physiologic markers of increased arousal, and increased acoustic startle response are all potential PTSD-associated traits that might be susceptible to genetic analysis. However, the capacity of these traits to distinguish PTSD from non-PTSD patients and their familial pattern must be better defined before they can be employed in genetic studies.