Affiliations: McGill, Canada
Journal reference: https://doi.org/10.1176/appi.ajp.2017.16111286
Summary: Brain plasticity is quite high during childhood, as brain development responds to changes in the environment. In this article, the effect of childhood abuse on brain development and genetics is explored.
During childhood our brains are malleable and can change in response to our environment. Experiencing adversity during this important period of brain development is therefore likely to lead to poor mental health outcomes, such as depression and anxiety, all the way into adulthood. Despite the fact that many studies have investigated the link between early life adversity and mental illness, several questions still remain. For instance, it is unclear how adversity in childhood leads to brain alterations that persist into adulthood. One potential explanation is that early life adversity is associated with persistent epigenetic, and therefore, gene expression changes. These molecular alterations can lead to persistent structural and functional changes to the cells within the brain.
Through the use of post-mortem human brain tissue, a team of researchers within the McGill Group for Suicide Studies have started to get a glimpse into the long-term epigenetic impacts of childhood abuse. In their recent study, published in American Journal of Psychiatry, the authors focused on the anterior cingulate cortex (ACC), a part of the brain that plays a crucial role in the regulation of mood and emotions. In order to understand the epigenetic changes that occur in the ACC as a result of childhood abuse, the researchers turned to a three group study design: subjects with a history of childhood abuse who were depressed and died by suicide, subjects who were depressed and died by suicide but did not have a history of childhood abuse, and control subjects without a history of childhood abuse, depression and/or suicide.
Focusing specifically on DNA methylation as their epigenetic mark of interest, the authors found global hyper- and hypomethylation in subjects with a history of childhood abuse. The most significant changes in DNA methylation were observed in genes (i.e. LINGO3, POU3F1 and ITGB1) known to play a crucial role in the myelination of axons (i.e. the process of insulating neurons via a fatty substance known as myelin). Since this insulation process is accomplished by a specific cell-type within the brain (i.e. oligodendrocytes), the researchers next turned to a cell-type specific approach for measuring DNA methylation. To this end, the researchers confirmed that childhood abuse associated changes in the epigenetic modifications were specific to oligodendrocytes, but not neurons.
In order to understand the functional impacts of the observed epigenetic changes, the authors next profiled global gene expression within the ACC. Focusing on a list of 55 oligodendrocyte and myelin related genes, the authors found that 35 of these genes (66%) were altered in individuals with a history of childhood abuse. To complement their human findings, the authors also used a well-established rodent model of maternal care, as a way to understand how variations in maternal care impact the expression of oligodendrocyte and myelin related genes. By comparing adult offspring raised with high versus low maternal care, the authors found a strong correlation between gene expression changes in rats raised with low maternal care and expression changes in human subjects with a history of childhood abuse.
Keeping in mind the molecular changes to oligodendrocyte and myelin related genes, their next logical step was to determine whether any structural changes could also be observed in myelin. Not surprisingly, myelin thickness was specifically reduced in individuals with a history of childhood abuse, independent of depression and suicide.
Altogether, these findings suggest that childhood abuse may, therefore, lead to persistent disruptions in the ability of oligodendrocytes to insulate crucial connections between brain areas involved in cognitive and emotional processing. These long-lasting changes may inevitably contribute to the emotional and behavioural issues that bridge the unclear link between childhood abuse and mental illness. The question of whether these changes are reversible through early intervention, however, remains to be explored.