Violent aggression predicted by multiple pre-adult environmental hits.
Marina MitjansJan SeidelMartin BegemannFabian BockhopJorge Moya-HiguerasVikas BansalJanina WesolowskiAnna SeelbachManuel Ignacio IbáñezFatka KovacevicOguzhan DuvarLourdes FañanásHannah-Ulrike WolfGenerós OrtetPeter ZwanzgerVerena KleinIna LangeAndreas TänzerManuela DudeckLars PenkeLudger Tebartz van ElstRobert A BittnerRichard SchmidmeierRoland FreeseRüdiger Müller-IsbernerJens WiltfangThomas BliesenerStefan BonnLuise PoustkaJürgen L MüllerBárbara AriasHannelore EhrenreichPublished in: Molecular psychiatry (2018)
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.
Keyphrases
- dna methylation
- mental illness
- human health
- mental health
- bipolar disorder
- histone deacetylase
- gene expression
- climate change
- computed tomography
- life cycle
- single cell
- randomized controlled trial
- genome wide
- depressive symptoms
- mass spectrometry
- magnetic resonance
- simultaneous determination
- childhood cancer
- binding protein
- tandem mass spectrometry