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

Stephen Z. Levine, Itzhak Levav, Rinat Yoffe, Inna Pugachova

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)236-240
Number of pages5
JournalSchizophrenia Research
Issue number1-3
StatePublished - 2014

Bibliographical note

Funding Information:
The current study is part of a larger project on Holocaust survivors jointly supported by non-overlapping funds from the Claims Conference and Israel Science Foundation. Through recovering the assets of the victims of the Holocaust, the Claims Conference enables organizations around the world to provide education about the Shoah and to preserve the memory of those who perished. This research was supported by the Israel Science Foundation (grant no. 130/13 ). Neither funding body provided feedback on this manuscript.


  • Epidemiology
  • Fetal origins
  • Holocaust
  • Longitudinal
  • Prenatal
  • Schizophrenia
  • Stress

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry


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