The effects of pre-natal-, early-life- and indirectly-initiated exposures to maximum adversities on the course of schizophrenia

Background: The effects of pre-natal-, early-life- and indirectly-initiated exposures to protracted maximum adversity on the course of schizophrenia are unknown. Aims: To compare the aforementioned Holocaust directly exposed subgroups with an indirectly exposed subgroup on the course of schizophrenia. Method: The study population were: Israeli Jews in-uterus or born in Nazi-occupied or dominated European nations by the end of the persecution of the Jews, who were alive in 1950, and who had a last discharge diagnosis of schizophrenia in the Israel National Psychiatric Case Registry by 2013 (N. =. 4933). The population was disaggregated into subgroups who (1) migrated after WWII and who had (1a) pre-natal (n. =. 584, 11.8%) and (1b) early-life (n. =. 3709, 75.2%) initiated exposures to the maximum adversities of the Holocaust, and (2) indirectly exposed individuals to the Holocaust who migrated before the Nazi-era persecution begun (n. =. 640, 13%). Recurrent event survival analyses were computed to examine the psychiatric re-hospitalization risk of the study subgroups, unadjusted and adjusted for age of onset of the disorder and sex. Results: The pre-natal initiated exposure subgroup had a significantly (p. <. 0.05) greater risk of psychiatric re-hospitalizations for schizophrenia than the other subgroups (unadjusted: HR. =. 3.39, 95% CI 2.95, 3.90; adjusted: HR. =. 2.28, 2.00, 2.60). This result replicated in sensitivity analyses for: Poland-born individuals, the years 1922 and 1935; and followed at least 10. years and to the year 2000. Conclusions: Pre-natal initiated exposure to the maximal adversity of the holocaust constitutes a consistent risk factor for a worse course of schizophrenia, a possible byproduct of neurodevelopment disruptions induced by maternal stress and/or famine and/or infections.