8/24/2023 0 Comments Psy on optical audio splitter![]() Characterization of early-life history was based on adapted Childhood Experiences of Care and Abuse interviews ( 10). Psychological autopsies were performed as described previously ( 9), with diagnoses assigned based on DSM-IV criteria. The groups were matched for age, postmortem interval, and brain pH ( 8) (see the data supplement that accompanies the online edition of this article). The results demonstrate that child abuse selectively affects small-diameter axons and their myelin sheaths.Īltogether, our studies reveal with unprecedented resolution the impact of child abuse on the anterior cingulate cortex epigenomic and histopathological architectures, and unveil oligodendrocytes and myelination as potential major substrates mediating the long-term consequences of child abuse.Īnterior cingulate cortex tissue was obtained from the Douglas-Bell Canada Brain Bank from 1) subjects who died suddenly without prolonged agonal state or medical illness, and with no psychiatric history (control group) 2) subjects who died by suicide in the context of a major depressive episode and had a history of severe child abuse (child abuse group) and 3) subjects who died by suicide in the context of a major depressive episode and had no history of child abuse (depressed group). Furthermore, we provide evidence showing that offspring of dams with low maternal care, a well-investigated rat model of early-life environmental variation, present myelin gene expression changes that correlate with the effects of child abuse in humans.įinally, associated cellular and subcellular changes were assessed using stereology and coherent anti-Stokes Raman scattering (CARS) microscopy, representing the first high-throughput analysis of individual myelinated axons in human subjects. ![]() Notably, these effects were absent in depressed suicide completers with no history of child abuse, strongly suggesting that they are not accounted for by psychopathology. We further demonstrated that part of the epigenetic adaptations in abused subjects selectively occurred in oligodendrocyte-lineage cells, but not in neurons. We first performed genome-wide screenings of DNA methylation and gene expression and found that child abuse was associated with a severe disruption of oligodendrocyte function. In the present study, focusing on the anterior cingulate cortex, we used a cohort of subjects with a history of severe child abuse (assessed through psychological autopsies ). We therefore hypothesized that child abuse, by affecting the epigenetic programming of key developmental processes, may lead to long-term structural and functional changes that potentiate the vulnerability to psychopathology. In particular, accumulating data suggest that patterns of DNA methylation, a major epigenetic mark, are progressively established during brain development and may be disrupted by early-life adversity ( 6). ![]() Recently, epigenetic regulation of gene expression has emerged as a mechanism of long-term genomic plasticity that has the potential to explain how early experiences may drive behavioral changes over the lifetime ( 5). While these studies bring invaluable insight into macrostructural adaptations associated with child abuse, underlying cellular and molecular alterations are largely unknown. These include evidence of cortical thinning, alterations in network centrality and functional connectivity, and disruption of white matter integrity (reviewed in reference 1). In particular, the anterior cingulate cortex, a critical region for the regulation of mood states, is among the brain areas most frequently associated with impairments in individuals with a history of child abuse. ![]() However, the neurobiological processes underlying this heightened vulnerability remain unclear.īrain imaging studies have described brain network activity and structural abnormalities associated with child abuse, which may ultimately affect various aspects of cognitive and emotional processing ( 1). In particular, it has been suggested that this relationship may be mediated by various traits, including neuroticism ( 2), high levels of impulsivity and aggressive behaviors ( 3), and high anxiousness trajectories ( 4), which are typically observed in depressed individuals with a history of abuse. Considerable clinical and epidemiological evidence shows that early-life adversity significantly increases the lifetime risk for stress-related psychiatric disorders, including depression and suicide. Child abuse is a major public health problem, affecting 5%−15% of all children in the Western world ( 1).
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