Violent aggression predicted by multiple pre-adult environmental hits

Abstract

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.

Advances in epigenetics link genetics to the environment and disease

“…Embryonic development and early life are two major susceptibility windows during which epigenetic programming is sensitive to environmental influences, such as diet, temperature, environmental toxins, maternal behaviour or childhood abuse 137 . Behavioural molecular genetics has identified a third susceptibility window, adolescence, during which adverse life experiences affect the risk of anxiety, depression and aggressive behaviour, associated with DNA methylation of specific genes 138 or with alterations in levels of HDAC1 139 . Furthermore, memory formation, a behavioural response to environmental stimuli, is associated with changes in histone and DNA modification at selected loci 140,141 .…”

Using Openly Accessible Resources to Strengthen Causal Inference in Epigenetic Epidemiology of Neurodevelopment and Mental Health

“…However, in some instances, conflicting evidence can be found [6] or only very weak evidence is provided, as seen in a study on post-traumatic stress and major depressive disorder [7]. With respect to neurodevelopment, DNA methylation differences were reported in relation to educational attainment and cognitive abilities measured in adulthood [8], attention-deficit hyperactivity disorder [9], oppositional defiant disorder [10], multiple risk behaviours [11], substance abuse [12], early-onset conduct disorder [13] and childhood physical aggression [14], with weaker evidence for an association with violent aggression and diagnosed autism spectrum disorders [15,16,17]. Neurological conditions that showed differences in blood-based DNA methylation when compared to controls include mesial temporal lobe epilepsy [18], narcolepsy [19] and Parkinson’s disease [20].…”

Bushmeat trade consequences predict higher anxiety, restraint, and dominance in chimpanzees

“…In the same line, other authors noted that early maternal rejection predicted increases in child fear and irritability (Lengua, ) and infants of postpartum depressed mothers expressed more negative emotions (Whiffen & Gotlib, ). Parental separation, the quality of parental behavior, childhood trauma, high stress exposure, and abuse may thus be specific vulnerability factors for several mental disorders such as post‐traumatic stress disorder (Pratchett & Yehuda, ), major depressive episodes (Aguilera et al, ; Cai et al, ), anxiety (Krugers et al, ), cognitive impairment (Barzilay et al, ), risk for phobia (Kendler, Neale, Kessler, Heath, & Eaves, ), violent aggression (Mitjans et al, ), and psychotic experiences (Alemany et al, ), among others. The increased risks of personality disorders were particularly characteristic of individuals separated from mothers before the age of five and more prevalent in men (Lahti et al, ), and the development of some of these disorders are mediated by personality organization (Fuchshuber, Hiebler‐Ragger, Kresse, Kapfhammer, & Unterrainer, ).…”