Summary: McGill researchers report those who suffer from traumatic experiences during childhood, like severe abuse, show significant abnormalities in the structure and cell function in the anterior cingulate cortex, an area of the brain associated with emotion and mood regulation. Researchers believe these changes may contribute to depressive disorders and suicidal ideations, often considered a long term effect of trauma suffered during early life.
Source: McGill University.
For the first time, researchers have been able to see changes in the neural structures in specific areas of the brains of people who suffered severe abuse as children.
Difficulties associated with severe childhood abuse include increased risks of psychiatric disorders such as depression, as well as high levels of impulsivity, aggressivity, anxiety, more frequent substance abuse, and suicide. Severe, non-random physical and/or sexual child abuse affects between 5-15 % of all children under the age of 15 in the Western world.
Researchers from the McGill Group for Suicide Studies, based at the Douglas Mental Health University Institute and McGill University’s Department of Psychiatry, published research in the American Journal of Psychiatry that suggests that the long-lasting effects of traumatic childhood experiences, like severe abuse, may be due to an impaired structure and functioning of cells in the anterior cingulate cortex. This is a part of the brain which plays an important role in the regulation of emotions and mood. The researchers believe that these changes may contribute to the emergence of depressive disorders and suicidal behaviour.
Crucial insulation for nerve fibres builds up during first two decades of life
For the optimal function and organization of the brain, electrical signals used by neurons may need to travel over long distances to communicate with cells in other regions. The longer axons of this kind are generally covered by a fatty coating called myelin. Myelin sheaths protect the axons and help them to conduct electrical signals more efficiently. Myelin builds up progressively (in a process known as myelination) mainly during childhood, and then continue to mature until early adulthood.
Earlier studies had shown significant abnormalities in the white matter in the brains of people who had experienced child abuse. (White matter is mostly made up of billions of myelinated nerve fibres stacked together.) But, because these observations were made by looking at the brains of living people using MRI, it was impossible to gain a clear picture of the white matter cells and molecules that were affected.
To gain a clearer picture of the microscopic changes which occur in the brains of adults who have experienced child abuse, and thanks to the availability of brain samples from the Douglas-Bell Canada Brain Bank (where, as well as the brain matter itself there is a lot of information about the lives of their donors) the researchers were able to compare post-mortem brain samples from three different groups of adults: people who had committed suicide who suffered from depression and had a history of severe childhood abuse (27 individuals); people with depression who had committed suicide but who had no history of being abused as children (25 individuals); and brain tissue from a third group of people who had neither psychiatric illnesses nor a history of child abuse (26 people).
Impaired neural connectivity may affect the regulation of emotions
The researchers discovered that the thickness of the myelin coating of a significant proportion of the nerve fibres was reduced ONLY in the brains of those who had suffered from child abuse. They also found underlying molecular alterations that selectively affect the cells that are responsible for myelin generation and maintenance. Finally, they found increases in the diameters of some of the largest axons among only this group and they speculate that together, these changes may alter functional coupling between the cingulate cortex and subcortical structures such as the amygdala and nucleus accumbens (areas of the brain linked respectively to emotional regulation and to reward and satisfaction) and contribute to altered emotional processing in people who have been abused during childhood.
The researchers conclude that adversity in early life may lastingly disrupt a range of neural functions in the anterior cingulate cortex. And while they don’t yet know where in the brain and when during development, and how, at a molecular level these effects are sufficient to have an impact on the regulation of emotions and attachment, they are now planning to explore this in further research.
Funding: Funding was provided by the Fondation Fyssen, the Fondation Bettencourt-Schueller, the Canadian Institutes of Health Research (CIHR), the American Foundation for Suicide Prevention (AFSP), the Fondation pour la Recherche Médicale, and the Fondation Deniker, the Fonds de Recherche du Québec-Santé (FRQS), the Canada Research Chair Program, NARSAD Distinguished Investigator Award, the NIH, and Pfizer.
Source: Bruno Geoffroy – McGill University
Image Source: NeuroscienceNews.com image is adapted from the McGill news release.
Original Research: Abstract for “Association of a History of Child Abuse With Impaired Myelination in the Anterior Cingulate Cortex: Convergent Epigenetic, Transcriptional, and Morphological Evidence” by Pierre-Eric Lutz, M.D., Ph.D., Arnaud Tanti, Ph.D., Alicja Gasecka, Ph.D., Sarah Barnett-Burns, B.Sc., John J. Kim, B.Sc., Yi Zhou, B.Sc., Gang G. Chen, Ph.D., Marina Wakid, B.Sc., Meghan Shaw, B.Sc., Daniel Almeida, B.Sc., Marc-Aurele Chay, B.Sc., Jennie Yang, M.Sc., Vanessa Larivière, D.C.S., Marie-Noël M’Boutchou, M.Sc., Léon C. van Kempen, Ph.D., Volodymyr Yerko, Ph.D., Josée Prud’homme, B.Sc., Maria Antonietta Davoli, M.Sc., Kathryn Vaillancourt, B.Sc., Jean-François Théroux, M.Sc., Alexandre Bramoullé, M.Sc., Tie-Yuan Zhang, Ph.D., Michael J. Meaney, Ph.D., Carl Ernst, Ph.D., Daniel Côté, Ph.D., Naguib Mechawar, Ph.D., and Gustavo Turecki, M.D., Ph.D. in American Journal of Psychiatry. Published online September 20 2017 doi:10.1176/appi.ajp.2017.16111286
Association of a History of Child Abuse With Impaired Myelination in the Anterior Cingulate Cortex: Convergent Epigenetic, Transcriptional, and Morphological Evidence
Child abuse has devastating and long-lasting consequences, considerably increasing the lifetime risk of negative mental health outcomes such as depression and suicide. Yet the neurobiological processes underlying this heightened vulnerability remain poorly understood. The authors investigated the hypothesis that epigenetic, transcriptomic, and cellular adaptations may occur in the anterior cingulate cortex as a function of child abuse.
Postmortem brain samples from human subjects (N=78) and from a rodent model of the impact of early-life environment (N=24) were analyzed. The human samples were from depressed individuals who died by suicide, with (N=27) or without (N=25) a history of severe child abuse, as well as from psychiatrically healthy control subjects (N=26). Genome-wide DNA methylation and gene expression were investigated using reduced representation bisulfite sequencing and RNA sequencing, respectively. Cell type–specific validation of differentially methylated loci was performed after fluorescence-activated cell sorting of oligodendrocyte and neuronal nuclei. Differential gene expression was validated using NanoString technology. Finally, oligodendrocytes and myelinated axons were analyzed using stereology and coherent anti-Stokes Raman scattering microscopy.
A history of child abuse was associated with cell type–specific changes in DNA methylation of oligodendrocyte genes and a global impairment of the myelin-related transcriptional program. These effects were absent in the depressed suicide completers with no history of child abuse, and they were strongly correlated with myelin gene expression changes observed in the animal model. Furthermore, a selective and significant reduction in the thickness of myelin sheaths around small-diameter axons was observed in individuals with history of child abuse.
The results suggest that child abuse, in part through epigenetic reprogramming of oligodendrocytes, may lastingly disrupt cortical myelination, a fundamental feature of cerebral connectivity.
“Association of a History of Child Abuse With Impaired Myelination in the Anterior Cingulate Cortex: Convergent Epigenetic, Transcriptional, and Morphological Evidence” by Pierre-Eric Lutz, M.D., Ph.D., Arnaud Tanti, Ph.D., Alicja Gasecka, Ph.D., Sarah Barnett-Burns, B.Sc., John J. Kim, B.Sc., Yi Zhou, B.Sc., Gang G. Chen, Ph.D., Marina Wakid, B.Sc., Meghan Shaw, B.Sc., Daniel Almeida, B.Sc., Marc-Aurele Chay, B.Sc., Jennie Yang, M.Sc., Vanessa Larivière, D.C.S., Marie-Noël M’Boutchou, M.Sc., Léon C. van Kempen, Ph.D., Volodymyr Yerko, Ph.D., Josée Prud’homme, B.Sc., Maria Antonietta Davoli, M.Sc., Kathryn Vaillancourt, B.Sc., Jean-François Théroux, M.Sc., Alexandre Bramoullé, M.Sc., Tie-Yuan Zhang, Ph.D., Michael J. Meaney, Ph.D., Carl Ernst, Ph.D., Daniel Côté, Ph.D., Naguib Mechawar, Ph.D., and Gustavo Turecki, M.D., Ph.D. in American Journal of Psychiatry. Published online September 20 2017 doi:10.1176/appi.ajp.2017.16111286