4.8 Article

Violent aggression predicted by multiple pre-adult environmental hits

期刊

MOLECULAR PSYCHIATRY
卷 24, 期 10, 页码 1549-1564

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NATURE PUBLISHING GROUP
DOI: 10.1038/s41380-018-0043-3

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资金

  1. Max Planck Society
  2. Max Planck Forderstiftung
  3. DFG (CNMPB)
  4. EXTRABRAIN EU-FP7
  5. Niedersachsen-Research Network on Neuroinfectiology (N-RENNT)
  6. EU-AIMS
  7. Innovative Medicines Initiative Joint Undertaking from the European Union's Seventh Framework Programme (FP7/2007-2013) [115300]
  8. EFPIA companies
  9. Autism Speaks
  10. Centro de Investigacion en Red de Salud Mental (CIBERSAM)
  11. Instituto de Salud Carlos III [PI16/00998]
  12. Comissionat per a Universitats i Recerca del DIUE [2014SGR1636]
  13. Spanish Ministry of Economy and Competitiveness (ES-EUEpiBrain) [SAF2015-71526-REDT]

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Early exposure to negative environmental impact shapes individual behavior and potentially contributes to any mental disease. We reported previously that accumulated environmental risk markedly decreases age at schizophrenia onset. Follow-up of matched extreme group individuals (<= 1 vs. >= 3 risks) unexpectedly revealed that high-risk subjects had >5 times greater probability of forensic hospitalization. In line with longstanding sociological theories, we hypothesized that risk accumulation before adulthood induces violent aggression and criminal conduct, independent of mental illness. We determined in 6 independent cohorts (4 schizophrenia and 2 general population samples) pre-adult risk exposure, comprising urbanicity, migration, physical and sexual abuse as primary, and cannabis or alcohol as secondary hits. All single hits by themselves were marginally associated with higher violent aggression. Most strikingly, however, their accumulation strongly predicted violent aggression (odds ratio 10.5). An epigenome-wide association scan to detect differential methylation of blood-derived DNA of selected extreme group individuals yielded overall negative results. Conversely, determination in peripheral blood mononuclear cells of histone-deacetylasel mRNA as 'umbrella mediator' of epigenetic processes revealed an increase in the high-risk group, suggesting lasting epigenetic alterations. Together, we provide sound evidence of a disease-independent unfortunate relationship between well-defined pre-adult environmental hits and violent aggression, calling for more efficient prevention.

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