BIOLOGY OF RISK AND PTSD IN HOLOCAUST SURVIVOR OFFSPRING

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Having identified parental PTSD as a risk factor for PTSD among offspring of Holocaust survivors, we are in a position to begin to examine biological correlates of risk for PTSD. Although there are certainly other approaches to studying risk in PTSD, such as studying characteristics in persons that are likely to be exposed to extreme trauma (e.g., firefighters, deployed soldiers), the status of such persons as "at risk" for PTSD is based on predicted trauma exposure. In contrast, in the case of offspring with parental PTSD, the vulnerability to PTSD is based on a historical variable that precedes, and is independent of, the offspring's experience of a focal trauma. By comparing at-risk offspring with and without PTSD, to offspring without the risk factor of parental PTSD, it is possible to address whether the biological variables associated with PTSD are similar to those associated with vulnerability. By additionally comparing Holocaust survivor offspring with subjects whose parents were not exposed to the Holocaust, it is possible to account for nonspecific 'transgenerational' effects related to extreme trauma exposure (i.e., the Holocaust) in parents. Our studies have focused on two major neuroendocrine systems -- the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). We have developed a battery of neuroendocrine assessments that have demonstrated significant differences between trauma survivors with PTSD when compared with survivors without PTSD, non-exposed subjects, and persons with other psychiatric disorders, particularly major depressive disorder (MDD). We have proposed that these findings can be explained as reflecting an enhanced negative feedback inhibition of the HPA axis in PTSD. In contrast, HPA axis alterations in depression have been explained as reflecting a reduced negative feedback inhibition of cortisol. The opportunity of examining risk provided by the proposed studies will magnify our ability to form conclusions about interrelationships among correlates of PTSD as they relate to vulnerability, exposure, and illness, and is therefore critical to understanding the pathophysiology of PTSD. The study of risk factors may ultimately help address the issue of why some individuals develop the symptoms of PTSD to lower magnitude events, whereas others fail to develop this disorder even in response to events of extremely high magnitude, such as, for example, the Holocaust. Finally, the identification of biological risk factors for PTSD may provide insights into prevention, prophylaxis and early treatment of this condition