Alternative Title: Adverse Childhood Experiences cause Epigenetic changes in the developing young Brain, leading to mental illness, depression, anger management issues, violent crime, incarceration and a multi generational vicious cycle of hopelessness and despair.
With only 5 percent of the world’s population, the United States has 25 percent of the world’s prison population. Why?
This study is the first to provide sound evidence, based on 6 separate cohorts, of a disease independent relationship between accumulation of multifaceted pre-adult environmental hits and violent aggression.
The name “correctional facility” is accurate from society’s perspective, but it is a delusional euphemism from the perspective of most inmates. According to the National Institute of Justice, three quarters of prisoners will be rearrested within five years of their release.
We lock up 7.16 out of 1,000 people in the United States, the highest rate of incarceration in the world.
The explosion of senseless mass violence in places that were once society’s most cherished communal places, schools, concert stadiums, public transportation and even houses of worship, is ripping apart the social fabric of American life.
The roots of violence at the level of brain biology need to be understood so that violence can be prevented.
Researchers have found a high incidence of genetic factors that increase impulsivity and anger in the violent prison population, and also an increased incidence of neurological abnormalities detectable with brain imaging. Studies of twins show that heredity accounts for over 60 percent of the risk for aggression.
The perpetrators of violent crime are almost always male. Humans have evolved through the survival-of-the-fittest struggle in the wild, evolved brain and bodily attributes that equip and predispose them to engage in aggression to provide and protect. This biological drive in males for aggression still exists in modern civilization.
Changes in society and in traditional male roles must be accompanied by new approaches to channel male aggression positively.
This can be reached by a path guided by neuroscience. Males have this biology of aggression for a reason, but it must be adapted to our current environment.
A new study finds that exposure to certain adverse events in early life, while the brain is undergoing maturation, greatly multiplies the odds of being institutionalized as an adult for violent aggression. They include poverty, social rejection from peer groups, cannabis and alcohol abuse, living in an urban environment, traumatic brain injury, immigration, conflict and violence in the home, and physical or sexual abuse.
. . . Scientific American
Molecular Psychiatry: Study
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 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. An epigenome wide association scan to detect differential methylation of blood-derived DNA of selected extreme group individuals yielded overall negative results. Conversely. detemination 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.
Early exposure to external risk factors like childhood maltreatment, sexual abuse or head trauma, but also living in urban environment or migration from other countries and cultures, have long been known or suspected to exert adverse effects on individual development and socioeconomic functioning. Moreover, these environmental risk factors seem to contribute to abnormal behavior and to severity and onset of mental illness, even though different risk factors may have different impact, dependent on the particular neuropsychiatric disease in focus. On top of these ‘primary factors‘ that are rather inevitable for the affected, ‘secondary’, avoidable risks add to the negative individual and societal outcome, namely cannabis and alcohol abuse.
Adverse experiences in adulthood, like exposure to violence, traumatic brain injury, or substance intoxication, can act as single triggers to increase the short term risk of violence in mentally ill individuals as much as in control subjects.
However, comprehensive studies, including large numbers of individuals and replication cohorts, on pre-adult accumulation of environmental risk factors and their long term consequences on human behavior do not exist.
In a recent report we showed that accumulation of environmental risks leads to a nearly 10 year earlier schizophrenia onset, demonstrating the substantial impact of the environment on mental disease, which by far outlasted any common genetic effects. To search for epigenetic signatures in blood of carefully matched extreme group subjects of this previous study we had to re-contact them. This reconnect led to the unforeseen observation that high risk subjects had 5 times higher probability to be hospitalized in forensic units compared to low risk subjects.
This finding stimulated the present work: Having the longstanding concepts of sociologists and criminologists in mind, we hypothesized that early accumulation of environmenml risk factors would lead to increased violent aggression and social rule-breaking in affected individuals, independent of any mental illness. To test this hypothesis, we explored environmental risk before the age of 18 years in 4 schizophrenia samples of me GRAS (Göttingen Research Association for Schizophrenia) data collection. Likewise, risk factors were assessed as available in 2 general population samples.
In all cohorts, accumulation of pre-adult environmental hits was highly significantly associated with lifetime conviction for violent acts or high psychopathy and aggression hostility scores as proxies of violent aggression and rule breaking.
As a first small hint of epigenetic alterations in our high risk subjects, histone deacelylasel (HDACI) mRNA was found increased in peripheral blood mono nuclear cells (PBMC).
Fig. 1 Multiple environmental hits before adulthood predict violent aggression in mentally ill subjects as well as in the general population. Results from 6 independent samples.
a – Distribution of forensic hospitalization in the discovery sample (see results) suggested a substantial impact of environmental risk accumulation on violent aggression, a finding replicated in the remaining GRAS sample (GRAS I males and females minus extreme group subjects of the discovery sample). Note the ‘stair pattem’ upon stepwise increase in risk factors; stacked charts illustrate risk factor composition in the respective groups (including all risk factors of each individual in the respective risk group), Each color represents a panicular risk (same legend for dg and jk); b – Brief presentation of the violent aggression severity score, VASS, ranging from no documented aggression to lethal consequences of violent aggression with relative weight given to severity of aggression and number of registered re occurrences. c – Highly significant intercorrelation of violent aggression measures used in the present paper. d – Application of VASS to risk accumulation in the discovery sample; Kmskal Wallis H test (two sided). e-g – Schizophrenia replication cohorts 1: ‘stair pattem‘ of aggression proxy in risk accumulation groups: all 12 test (one sided). h – Comparative presentation of subjects (%) with violent aggression in risk accumulation groups across schizophrenia cohorts. i – Comparative presentation of subjects (%) with violent aggression before (pre morbid, ‘early’) or after schizophrenia onset (‘late‘) vs. individuals without evidence of aggression (‘no’) in risk accumulation groups of the discovery sample. j-k – General population replication cohorts IV and V: ‘stair pattern‘ of aggression proxies, LSRP secondary psy chopathy score (j) and aggression hostility factor of ZKFQ 50 CC (k) in risk accumulation groups; Kruskal Wallis 1 test (one sided). l – HDACI mRNA levels in PBMC of male extreme group subjects as available for analysis; Student‘s t test (one sided).
The present work was initiated based on the observation in a schizophrenia cohort that accumulation of environmental risk factors before adulthood promotes the likelihood of later forensic hospitalization, interpreted as indicator of violent aggression. This interpretation and the effect of risk accumulation were consolidated using direct scoring of aggression over lifetime or, as aggression proxies, forensic hospitalization and conviction for battery, sexual assault, manslaughter or murder. or respective psychopathology measures in 4 independent schizophrenia cohorts and 2 general population samples. Importantly, our data support the concept of a disease independent development of violent aggression in subjects exposed to multiple pre adult environmental risk factors.
Whereas a vast amount of literature on single environmental risk factors reports consequences for abnormal behavior and mental illness, publications on pre-adult risk accumulation are scarce and mostly based on closely interrelated social/familial risk factors. Also, risk and consequence are often not clearly defined. Studies including larger, comprehensively characterized datasets and replication samples do not exist.
The present work is the first to provide sound evidence, based on 6 separate cohorts, of a disease independent relationship between accumulation of multifaceted pre-adult environmental hits and violent aggression.
The overall societal damage is enormous, and we note that mentally ill individuals who re-enter the community from prison are even more at risk for unemployment, homelessness, and criminal recidivism. These results should encourage better precautionary measures, including intensified research on protective factors which is still underrepresented.
In the psychosociological literature, the so called externalizing behavior in childhood includes hostile and aggressive physical behavior toward others, impulsivity, hyperactivity, and noncompliance with limit setting. The respective risk factors are all highly plausible, yet often theoretical, and derived from 4 broad domains: child risk factors (e.g., adverse temperament, genetic and gender risk), sociocultural risks (e.g., poverty, stressful life events), parenting and caregiving (e.g., confiict and violence at home, physical abuse), and children’s peer experiences (e.g., instable relationships, social rejection). A full model of the development of conduct problems has been suggested to include at least these 4 domains.
The risk factors analyzed in the present study are perhaps somewhat clearer defined but partially related to and overlapping across these domains. Urbanicity, migration, cannabis and alcohol reflect sociocultural input but also peer experience, and physical or sexual abuse belong to the parenting/caregiver aspect.
Certainly, there are many more, still undiscovered risk and numerous protective factors, potentially explaining why ‘only’ 40-50% of high risk individuals in our schizophrenia samples fulfill criteria of violent aggression.
We note that this study does not include genetic data analysis or correction for any genetic impact. The genetic influence on aggression, however, may be of considerable relevance for the individual, even though highly heterogeneous as for essentially all behavioral traits. Heritability of aggression, estimated from twin studies, reaches >60%. In fact, 50% of individuals with violent aggression upon pre-adult risk accumulation in the present study means another 50% without detectable aggression. This consistent finding across samples likely indicates that genetic predisposition is prerequisite for whichever behavioral consequence. Individuals without genetic predisposition and/or with more protective factors (genetic and environmental) may not react with violent aggression to accumulated environmental risk.
Importantly, the obvious gender effect may be a matter of degree rather than of pattern. In fact, the etiology of externalizing behavior problems is similar for girls and boys, as is the consequence of risk accumulation in the present study for males and females.
The risk factors of the sociological domains seem to be stable predictors over time, to some degree interchangeable, pointing to many pathways leading to the same outcome (principle of equifinality). The interchangeability is highly interesting also with respect to potential biological mechanisms. It appears that any of the here investigated hits alone, independent of its kind, can be compensated for but that higher risk load increases the probability of violent aggression.
Also for that reason, we are weighing risk factors equally in the present study. This could theoretically create some bias. However, to be able to estimate the true effect size of each specific factor separately on violent aggression and subsequently weigh all factors in a more proper way, much larger samples sizes would be needed that are presently not available anywhere in the world.
In contrast to the marginal influence of genome wide association data on mental disease in GRAS, the accumulated environmental impact on development of violent aggression is huge, reflected by odds ratios of >10. When striking at a vulnerable time of brain development, namely around/before puberty, the environmental input may ‘non specifically’ affect any predisposed individual. The hypothetical biological mechanisms underlying this accumulation effect in humans may range from alterations in neuroendocrine and neurotransmitter systems, neuronal/ synaptic plasticity and neurogenesis to changes in the adaptive immune system and interference with developmental myelination, affecting brain connectivity and network function.
Our approach to detect methylation changes in blood using an epigenome wide association scan was unsuccessful despite matched extreme group comparison, likely due to the small sample size, and perhaps the etiological/pathogenetic complexity of accumulated risks. Changes in brain, not accessible here for analysis, can certainly not be excluded. Interestingly, however, HDAC1 mRNA levels in PBMC of male extreme group subjects were increased in the high risk compared to the low risk group. This finding confirms peripheral HDAC1 mRNA levels as a more robust readout of epigenetic alterations in relatively small sample sizes, as compared to specific methylation sites in epigenome wide association scans or even in candidate genes. To gain further mechanistic insight and thereby develop in addition to prevention measures novel individualized treatment concepts, animal studies modeling risk accumulation seem unavoidable.
To conclude, this study should motivate sociopolitical actions, aiming at identifying individuals at risk and improving precautionary measures. Effective violence prevention strategies start early and include family focused and school based programs. Additional risk factors, interchangeable in their long term consequences, like urbanicity, migration, and substance abuse, should be increasingly considered. Health care providers are essential for all of these prevention concepts. More research on protective factors and resilience should be launched. Animal studies need to be supported that model risk accumulation for mechanistic insight into brain alterations leading to aggression, and for developing new treatment approaches, also those targeting reversal of epigenetic alterations. As a novel concept, scientific efforts on ‘phenaryptyping of the environment’, should be promoted to achieve more fundamental risk estimation and more effective prevention in the future.
Read the complete study here: Violent aggression predicted by multiple pre-adult environmental hits