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Abstract

Objective:

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.

Method:

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.

Results:

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.

Conclusions:

The results suggest that child abuse, in part through epigenetic reprogramming of oligodendrocytes, may lastingly disrupt cortical myelination, a fundamental feature of cerebral connectivity.

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Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Pages: 1185 - 1194
PubMed: 28750583

History

Received: 21 November 2016
Revision received: 7 April 2017
Accepted: 4 May 2017
Published online: 28 July 2017
Published in print: December 01, 2017

Keywords

  1. Neuropathology
  2. Suicide
  3. Mood Disorders-Unipolar
  4. Molecular Biology

Authors

Details

Pierre-Eric Lutz, M.D., Ph.D.
From the McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal; Institut Universitaire en Santé Mentale de Québec, Quebec; Centre d’Optique, Photonique, et Laser, Université Laval, Quebec; Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal; the Department of Psychiatry, McGill University, Montreal; the Sackler Program for Epigenetics and Psychobiology at McGill University and the Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal.
Arnaud Tanti, Ph.D.
From the McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal; Institut Universitaire en Santé Mentale de Québec, Quebec; Centre d’Optique, Photonique, et Laser, Université Laval, Quebec; Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal; the Department of Psychiatry, McGill University, Montreal; the Sackler Program for Epigenetics and Psychobiology at McGill University and the Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal.
Alicja Gasecka, Ph.D.
From the McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal; Institut Universitaire en Santé Mentale de Québec, Quebec; Centre d’Optique, Photonique, et Laser, Université Laval, Quebec; Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal; the Department of Psychiatry, McGill University, Montreal; the Sackler Program for Epigenetics and Psychobiology at McGill University and the Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal.
Sarah Barnett-Burns, B.Sc.
From the McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal; Institut Universitaire en Santé Mentale de Québec, Quebec; Centre d’Optique, Photonique, et Laser, Université Laval, Quebec; Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal; the Department of Psychiatry, McGill University, Montreal; the Sackler Program for Epigenetics and Psychobiology at McGill University and the Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal.
John J. Kim, B.Sc.
From the McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal; Institut Universitaire en Santé Mentale de Québec, Quebec; Centre d’Optique, Photonique, et Laser, Université Laval, Quebec; Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal; the Department of Psychiatry, McGill University, Montreal; the Sackler Program for Epigenetics and Psychobiology at McGill University and the Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal.
Yi Zhou, B.Sc.
From the McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal; Institut Universitaire en Santé Mentale de Québec, Quebec; Centre d’Optique, Photonique, et Laser, Université Laval, Quebec; Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal; the Department of Psychiatry, McGill University, Montreal; the Sackler Program for Epigenetics and Psychobiology at McGill University and the Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal.
Gang G. Chen, Ph.D.
From the McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal; Institut Universitaire en Santé Mentale de Québec, Quebec; Centre d’Optique, Photonique, et Laser, Université Laval, Quebec; Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal; the Department of Psychiatry, McGill University, Montreal; the Sackler Program for Epigenetics and Psychobiology at McGill University and the Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal.
Marina Wakid, B.Sc.
From the McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal; Institut Universitaire en Santé Mentale de Québec, Quebec; Centre d’Optique, Photonique, et Laser, Université Laval, Quebec; Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal; the Department of Psychiatry, McGill University, Montreal; the Sackler Program for Epigenetics and Psychobiology at McGill University and the Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal.
Meghan Shaw, B.Sc.
From the McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal; Institut Universitaire en Santé Mentale de Québec, Quebec; Centre d’Optique, Photonique, et Laser, Université Laval, Quebec; Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal; the Department of Psychiatry, McGill University, Montreal; the Sackler Program for Epigenetics and Psychobiology at McGill University and the Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal.
Daniel Almeida, B.Sc.
From the McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal; Institut Universitaire en Santé Mentale de Québec, Quebec; Centre d’Optique, Photonique, et Laser, Université Laval, Quebec; Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal; the Department of Psychiatry, McGill University, Montreal; the Sackler Program for Epigenetics and Psychobiology at McGill University and the Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal.
Marc-Aurele Chay, B.Sc.
From the McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal; Institut Universitaire en Santé Mentale de Québec, Quebec; Centre d’Optique, Photonique, et Laser, Université Laval, Quebec; Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal; the Department of Psychiatry, McGill University, Montreal; the Sackler Program for Epigenetics and Psychobiology at McGill University and the Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal.
Jennie Yang, M.Sc.
From the McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal; Institut Universitaire en Santé Mentale de Québec, Quebec; Centre d’Optique, Photonique, et Laser, Université Laval, Quebec; Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal; the Department of Psychiatry, McGill University, Montreal; the Sackler Program for Epigenetics and Psychobiology at McGill University and the Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal.
Vanessa Larivière, D.C.S.
From the McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal; Institut Universitaire en Santé Mentale de Québec, Quebec; Centre d’Optique, Photonique, et Laser, Université Laval, Quebec; Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal; the Department of Psychiatry, McGill University, Montreal; the Sackler Program for Epigenetics and Psychobiology at McGill University and the Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal.
Marie-Noël M’Boutchou, M.Sc.
From the McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal; Institut Universitaire en Santé Mentale de Québec, Quebec; Centre d’Optique, Photonique, et Laser, Université Laval, Quebec; Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal; the Department of Psychiatry, McGill University, Montreal; the Sackler Program for Epigenetics and Psychobiology at McGill University and the Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal.
Léon C. van Kempen, Ph.D.
From the McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal; Institut Universitaire en Santé Mentale de Québec, Quebec; Centre d’Optique, Photonique, et Laser, Université Laval, Quebec; Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal; the Department of Psychiatry, McGill University, Montreal; the Sackler Program for Epigenetics and Psychobiology at McGill University and the Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal.
Volodymyr Yerko, Ph.D.
From the McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal; Institut Universitaire en Santé Mentale de Québec, Quebec; Centre d’Optique, Photonique, et Laser, Université Laval, Quebec; Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal; the Department of Psychiatry, McGill University, Montreal; the Sackler Program for Epigenetics and Psychobiology at McGill University and the Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal.
Josée Prud’homme, B.Sc.
From the McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal; Institut Universitaire en Santé Mentale de Québec, Quebec; Centre d’Optique, Photonique, et Laser, Université Laval, Quebec; Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal; the Department of Psychiatry, McGill University, Montreal; the Sackler Program for Epigenetics and Psychobiology at McGill University and the Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal.
Maria Antonietta Davoli, M.Sc.
From the McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal; Institut Universitaire en Santé Mentale de Québec, Quebec; Centre d’Optique, Photonique, et Laser, Université Laval, Quebec; Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal; the Department of Psychiatry, McGill University, Montreal; the Sackler Program for Epigenetics and Psychobiology at McGill University and the Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal.
Kathryn Vaillancourt, B.Sc.
From the McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal; Institut Universitaire en Santé Mentale de Québec, Quebec; Centre d’Optique, Photonique, et Laser, Université Laval, Quebec; Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal; the Department of Psychiatry, McGill University, Montreal; the Sackler Program for Epigenetics and Psychobiology at McGill University and the Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal.
Jean-François Théroux, M.Sc.
From the McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal; Institut Universitaire en Santé Mentale de Québec, Quebec; Centre d’Optique, Photonique, et Laser, Université Laval, Quebec; Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal; the Department of Psychiatry, McGill University, Montreal; the Sackler Program for Epigenetics and Psychobiology at McGill University and the Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal.
Alexandre Bramoullé, M.Sc.
From the McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal; Institut Universitaire en Santé Mentale de Québec, Quebec; Centre d’Optique, Photonique, et Laser, Université Laval, Quebec; Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal; the Department of Psychiatry, McGill University, Montreal; the Sackler Program for Epigenetics and Psychobiology at McGill University and the Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal.
Tie-Yuan Zhang, Ph.D.
From the McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal; Institut Universitaire en Santé Mentale de Québec, Quebec; Centre d’Optique, Photonique, et Laser, Université Laval, Quebec; Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal; the Department of Psychiatry, McGill University, Montreal; the Sackler Program for Epigenetics and Psychobiology at McGill University and the Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal.
Michael J. Meaney, Ph.D.
From the McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal; Institut Universitaire en Santé Mentale de Québec, Quebec; Centre d’Optique, Photonique, et Laser, Université Laval, Quebec; Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal; the Department of Psychiatry, McGill University, Montreal; the Sackler Program for Epigenetics and Psychobiology at McGill University and the Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal.
Carl Ernst, Ph.D.
From the McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal; Institut Universitaire en Santé Mentale de Québec, Quebec; Centre d’Optique, Photonique, et Laser, Université Laval, Quebec; Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal; the Department of Psychiatry, McGill University, Montreal; the Sackler Program for Epigenetics and Psychobiology at McGill University and the Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal.
Daniel Côté, Ph.D.
From the McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal; Institut Universitaire en Santé Mentale de Québec, Quebec; Centre d’Optique, Photonique, et Laser, Université Laval, Quebec; Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal; the Department of Psychiatry, McGill University, Montreal; the Sackler Program for Epigenetics and Psychobiology at McGill University and the Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal.
Naguib Mechawar, Ph.D. [email protected]
From the McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal; Institut Universitaire en Santé Mentale de Québec, Quebec; Centre d’Optique, Photonique, et Laser, Université Laval, Quebec; Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal; the Department of Psychiatry, McGill University, Montreal; the Sackler Program for Epigenetics and Psychobiology at McGill University and the Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal.
Gustavo Turecki, M.D., Ph.D. [email protected]
From the McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal; Institut Universitaire en Santé Mentale de Québec, Quebec; Centre d’Optique, Photonique, et Laser, Université Laval, Quebec; Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal; the Department of Psychiatry, McGill University, Montreal; the Sackler Program for Epigenetics and Psychobiology at McGill University and the Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal.

Notes

Address correspondence to Dr. Turecki ([email protected]) and Dr. Mechawar ([email protected]).

Author Contributions

The first two authors contributed equally to this article.

Competing Interests

The authors report no financial relationships with commercial interests.

Funding Information

Canadian Institutes of Health Research10.13039/501100000024: FDN148374, MOP-111022, MOP11260, MOP119429, MOP119430, MOP93775

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