Distinct influence of maternal and paternal PTSD on Holocaust offspring

Rationale : Holocaust offspring are at greater risk for the development of Posttraumatic stress disorder (PTSD) than comparison subjects, and the increased vulnerability appears to be associated with maternal PTSD. Paternal PTSD is associated with increased vulnerability to depression in Holocaust offspring. In prior studies, neuroendocrine alterations have been observed in Holocaust offspring that resemble those described in association with PTSD and PTSD risk. Holocaust offspring were more likely to show cortisol hypersuppression on the dexamethasone suppression test (DST) in association with parental PTSD even if offspring had not developed lifetime PTSD. These data imply an enhanced glucocorticoid receptor responsiveness that might be associated with PTSD risk, as has been demonstrated in other populations at risk for PTSD, such as soldiers preparing to deploy for combat. More recently, it has been of interest to consider the differential contributions of maternal vs. paternal PTSD on offspring neuroendocrinology. Such work may identify putative epigenetic changes underlying neuroendocrine alterations associated with PTSD risk. Methods : The current study examined glucocorticoid responsiveness as reflected by the 0.50 mg dexamethasone suppression test (DST) and the lysozyme stimulation test (LST) in 81 Holocaust offspring, the majority of whom (73%) had two Holocaust exposed parents. The offspring were subdivided based on maternal and paternal PTSD. The LST is an in vitro test of glucocorticoid responsiveness carried out in live cultured lymphocytes exposed to varying doses of dexamethasone (DEX) for which a lower IC50-DEX for lysozyme inhibition indicates increased GR responsiveness. Results : In this sample, there was a significant correlation between the cortisol response to DEX (expressed as cortisol decline from pre- to post-DEX), and the lysozyme IC50-DEX (r= 0.521, df = 43, p≤0.0005; controlling for age, gender, BMI and DEX levels), reflecting that the cortisol response following ingestion of an oral dose of 0.5 mg DEX resulted in a similar response to that associated with exposing cultured lymphocytes from the same individual to DEX in vitro. There was a main effect [F(1,42) = 4.48, p=0.04] of paternal PTSD on the DST, controlling for age, gender, BMI, DEX levels, and parental Holocaust exposure (i.e., to control for those cases in which a non-PTSD parent was also not a Holocaust survivor). This main effect demonstrated that offspring with only paternal PTSD had evidence of diminished cortisol suppression (non-suppression) compared to the t