Violent aggression predicted by multiple pre-adult environmental hits

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) une...

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Bibliographic Details
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
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Summary:	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.
ISSN:	1359-4184 1476-5578
DOI:	10.1038/s41380-018-0043-3