Violent aggression predicted by multiple pre-adult environmental hits

• Published in: Molecular psychiatry Vol. 24; no. 10; pp. 1549 - 1564
• Main Authors: Mitjans, Marina, Seidel, Jan, Begemann, Martin, Bockhop, Fabian, Moya-Higueras, Jorge, Bansal, Vikas, Wesolowski, Janina, Seelbach, Anna, Ibáñez, Manuel Ignacio, Kovacevic, Fatka, Duvar, Oguzhan, Fañanás, Lourdes, Wolf, Hannah-Ulrike, Ortet, Generós, Zwanzger, Peter, Klein, Verena, Lange, Ina, Tänzer, Andreas, Dudeck, Manuela, Penke, Lars, van Elst, Ludger Tebartz, Bittner, Robert A., Schmidmeier, Richard, Freese, Roland, Müller-Isberner, Rüdiger, Wiltfang, Jens, Bliesener, Thomas, Bonn, Stefan, Poustka, Luise, Müller, Jürgen L., Arias, Bárbara, Ehrenreich, Hannelore
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-10-2019; Nature Publishing Group
• Subjects: 38/39; 38/77; 631/378; 692/53; 692/699/476; Abuse; Accumulation; Adolescent; Adult; Adverse Childhood Experiences; Aggression; Aggression - psychology; Aggressiveness (Psychology); Alcohols; Analysis; Behavioral Sciences; Biological Psychology; Cannabis; DNA methylation; Environmental impact; Environmental risk; Epigenesis, Genetic - genetics; Epigenetic inheritance; Epigenetics; Exposure; Exposure to Violence - psychology; Female; Forensic science; Histone Deacetylase 1 - genetics; Humans; Leukocytes (mononuclear); Male; Medicine; Medicine & Public Health; Mental disorders; Mental illness; mRNA; Neurosciences; Odds Ratio; Peripheral blood mononuclear cells; Pharmacotherapy; Psychiatry; Psychological aspects; Risk Factors; Risk groups; Schizophrenia; Schizophrenia - epidemiology; Schizophrenia - genetics; Sexual assault; Violence - psychology
• DOI: 10.1038/s41380-018-0043-3
• EISSN: 1476-5578
• ISSN: 1359-4184

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-deacetylase1 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.