May 7, 2008 A team of McGill University scientists has discovered important differences between the brains of suicide victims and so-called normal brains. Although the genetic sequence was identical in the suicide and non-suicide brains, there were differences in their epigenetic marking – a chemical coating influenced by environmental factors.
All of the 13 suicide victims in the study had experienced abuse as children.
“It’s possible the changes in epigenetic markers were caused by the exposure to childhood abuse, although in humans it’s difficult to establish causality between early childhood and epigenetic markers, in the way we have established this in animal subjects,” said Moshe Szyf, a professor in McGill’s Department of Pharmacology and Therapeutics. “The big remaining questions are whether scientists could detect similar changes in blood DNA – which could lead to diagnostic tests – and whether we could design interventions to erase these differences in epigenetic markings”.
In the first study of its kind, Szyf, a professor in the Department of Pharmacology and Therapeutics; Gustavo Turecki, Department of Psychiatry who practices at the Douglas Hospital; Michael Meaney, a professor in the Departments of Psychiatry and Neurology and Neurosurgery, who is also at the Douglas Hospital; and McGill postdoctoral research fellow Patrick McGowan have built on their world-renowned epigenetics work to uncover differences in the DNA in the brains of a group of male suicide victims from Quebec. The all-McGill study is set to be published in the May 6, 2008 edition of the online journal Public Library of Science (PLoS ONE).
Epigenetics is the study of changes in the function of genes that don’t involve changes in the sequences of DNA. The DNA is inherited from our parents; it remains fixed throughout life and is identical in every part of the body. During gestation, however, the genes in our DNA are marked by a chemical coating called DNA methylation. These marks are somewhat sensitive to one’s environment, especially early in life.
The epigenetic marks punctuate the DNA and program it to express the right genes at the appropriate time and place.
The researchers examined a set of genes that code for rRNA, a basic component of the machinery that creates protein in cells. Protein synthesis is critical for learning, memory and the building of new connections in the brain; it can affect decision-making and other behaviour. The scientists found that rRNA can be regulated epigenetically.
In previous studies in laboratory rats, the group proved that simple maternal behaviour during early childhood has a profound effect on genes and behaviour in ways that are sustained throughout life. However, these effects on gene expression and stress responses can also be reversed in adult life through treatments known to affect the genomic marking known as DNA methylation.
The brain samples in the latest study came from the Quebec Suicide Brain Bank, administered by Dr. Turecki of the Douglas Mental Health University Institute. With the support of the Bureau du Coroner du Québec (Office of the Chief Medical Examiner), the McGill Group for Suicide Studies (MGSS) founded the Quebec Suicide Brain Bank (QSBB) at the Douglas Mental Health University Institute, to promote studies on the phenomenon of suicide. Research carried out on brain tissue can help develop intervention and prevention programs to help people suffering mental distress and who are at risk of committing suicide.
The research was funded by the Canadian Institutes of Health Research.
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- Patrick O. McGowan, Aya Sasaki, Tony C. T. Huang, Alexander Unterberger, Matthew Suderman, Carl Ernst, Michael J. Meaney, Gustavo Turecki, Moshe Szyf, Jörg Hoheisel. Promoter-Wide Hypermethylation of the Ribosomal RNA Gene Promoter in the Suicide Brain. PLoS ONE, 2008; 3 (5): e2085 DOI: 10.1371/journal.pone.0002085
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