Schizophrenia in Offspring of Holocaust Survivors: Intergenerational Effects of Preconception Parental Trauma Within the Jerusalem Perinatal Study.

Abstract

The role of parental preconception trauma in the pathogenesis of psychiatric disorders remains unclear. The authors investigated whether offspring of Holocaust survivors, born years later, are at increased risk of schizophrenia. Data from the Jerusalem Perinatal Study (1964-1976) were linked to Israel's National Psychiatric Registry. Parents from European countries under Nazi rule who immigrated to Israel after the anti-Jewish persecutions began were classified as exposed. Parents were further categorized by their own age (≤5 or >5 years) when the persecutions began. Unexposed parents were of European descent not living under Nazi rule. Two offspring subsamples were assembled: 14,759 offspring of 7,316 mothers and 18,085 offspring of 8,833 fathers, of whom 3,913 had exposed mothers and 5,672 had exposed fathers. For each offspring subsample, Cox models were used to analyze time to first schizophrenia hospitalization. In minimally adjusted models, offspring of parents who were older than age 5 at exposure showed elevated schizophrenia rates (maternal exposure: hazard ratio=2.71, 95% CI=1.60-4.61; paternal exposure: hazard ratio=1.52, 95% CI=1.01-2.28). No associations were observed in offspring whose parents were exposed earlier (≤5 years). Adjustments for sociodemographic variables diminished the association of paternal exposure at age >5, whereas association with maternal exposure remained strong (hazard ratio=2.38, 95% CI=1.20-4.70) and withstood further adjustments for mother's psychiatric hospitalization (hazard ratio=3.73, 95% CI=1.87-7.43) and other covariates. Offspring of mothers who were older than age 5 when Nazi persecutions began showed over a twofold increase in schizophrenia risk, underscoring the potential impact of trauma and its timing during the preconception period in the pathogenesis of schizophrenia.