title: The effects of pre-natal-, early-life- and indirectly-initiated exposures to maximum adversities on the course of schizophrenia.
abstract: BACKGROUND
  The effects of pre-natal-, early-life- and indirectly-initiated exposures to protracted maximum adversity on the course of schizophrenia are unknown.
  
  
  OBJECTIVE
  To compare the aforementioned Holocaust directly exposed subgroups with an indirectly exposed subgroup on the course of schizophrenia.
  
  
  METHODS
  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.
authors: Department of Community Mental Health, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel. Electronic address: slevine@univ.haifa.ac.il.
authors: Stephen Z
authors: SZ
authors: Levine
authors: Department of Community Mental Health, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel.
authors: Itzhak
authors: I
authors: Levav
authors: Department of Information and Evaluation, Ministry of Health, Jerusalem, Israel.
authors: Rinat
authors: R
authors: Yoffe
authors: Department of Information and Evaluation, Ministry of Health, Jerusalem, Israel.
authors: Inna
authors: I
authors: Pugachova
mesh_terms: D017668:Age of Onset; D002649:Child Abuse; D002675:Child, Preschool; D015331:Cohort Studies; D005060:Europe / Q000208:ethnology; D005260:Female; D005500:Follow-Up Studies; D017767:Holocaust; D006760:Hospitalization; D006801:Humans; D007223:Infant; D007557:Israel / Q000453:epidemiology; D007585:Jews; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology*; D012042:Registries; D012307:Risk Factors; D012559:Schizophrenia / Q000453:epidemiology* / Q000628:therapy; D012680:Sensitivity and Specificity; D012737:Sex Factors; D013315:Stress, Psychological / Q000453:epidemiology*
keywords: Epidemiology; Fetal origins; Holocaust; Longitudinal; Prenatal; Schizophrenia; Stress