Genome-Wide Methylation Changes in the Brains of Suicide Completers
Abstract
Objective Gene expression changes have been reported in the brains of suicide completers. More recently, differences in promoter DNA methylation between suicide completers and comparison subjects in specific genes have been associated with these changes in gene expression patterns, implicating DNA methylation alterations as a plausible component of the pathophysiology of suicide. The authors used a genome-wide approach to investigate the extent of DNA methylation alterations in the brains of suicide completers. Method Promoter DNA methylation was profiled using methylated DNA immunoprecipitation (MeDIP) followed by microarray hybridization in hippocampal tissue from 62 men (46 suicide completers and 16 comparison subjects). The correlation between promoter methylation and expression was investigated by comparing the MeDIP data with gene expression profiles generated through mRNA microarray. Methylation differences between groups were validated on neuronal and nonneuronal DNA fractions isolated by fluorescence-assisted cell sorting. Results The authors identified 366 promoters that were differentially methylated in suicide completers relative to comparison subjects (273 hypermethylated and 93 hypomethylated). Overall, promoter methylation differences were inversely correlated with gene expression differences. Functional annotation analyses revealed an enrichment of differential methylation in the promoters of genes involved, among other functions, in cognitive processes. Valid…
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Decreased hippocampal GR expression was found in samples from suicide completers with histories of childhood maltreatment compared with controls.
“We65,120 showed decreased hippocampal GR expression in samples from suicide completers with histories of childhood maltreatment compared with controls (sudden, involuntary fatalities).”
From Early life adversity and the epigenetic programming of hypothalamic-pituitary-adrenal function (2014) · cites this paper as [120]
There was significantly increased DNA methylation of the exon 1H promoter in hippocampal samples from both controls and suicide victims without a history of maltreatment by comparison to those positive for maltreatment.
“There was significantly increased DNA methylation of the exon 1H promoter in hippocampal samples from both controls and suicide victims without a history of maltreatment by comparison to those positive for maltreatment.”
From Early life adversity and the epigenetic programming of hypothalamic-pituitary-adrenal function (2014) · cites this paper as [120]
Most differentially methylated sites were found within putative transcription factor binding sites.
“Interestingly, most differentially methylated sites were found within putative transcription factor binding sites.”
From Early life adversity and the epigenetic programming of hypothalamic-pituitary-adrenal function (2014) · cites this paper as [120]
Methylation of the exon 1H promoter was positively correlated with hippocampal GR expression.
“And the methylation of the exon 1H promoter was positively correlated with hippocampal GR expression.”
From Early life adversity and the epigenetic programming of hypothalamic-pituitary-adrenal function (2014) · cites this paper as [120]
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- Authors
- Labonté, B., Suderman, M., Maussion, G., Lopez, J. P., Navarro-Sánchez, L., Yerko, V., Mechawar, N., Szyf, M., Meaney, M. J., & Turecki, G.
- Affiliations
- From the McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal; the Departments of Psychiatry, Pharmacology and Therapeutics, Human Genetics, and Neurology and Neurosurgery and the McGill Centre for Bioinformatics, McGill University, Montreal; the Singapore Institute for Clinical Sciences, Singapore; and the Molecular Genetics Unit, Institute of Biomedicine of Valencia, Spain.
- Douglas Mental Health University Institute (CA)
- ORCID
- Venue
- American Journal of Psychiatry
- Published
- 2013-05
- Volume
- 170
- Issue
- 5
- Pages
- 511-520
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- OpenAlex
- W2024518588
- Cited by
- 212
- References
- 10
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 9 · 2023: 5 · 2022: 6 · 2021: 14 · 2020: 16 · 2019: 11 · 2018: 43 · 2017: 16 · 2016: 23 · 2015: 22 · 2014: 34 · 2013: 5
- FWCI
- 12.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research (84291_1, MOP84291)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- suicide, promoter methylation, epigenetics, hippocampus, brain gene expression, hypermethylation, hypomethylation, cognitive processes, suicide risk
- MeSH terms
- Adult, Hippocampus, Humans, Male, Neurons, Promoter Regions, Genetic, Suicide, Genome, Human, Case-Control Studies, DNA Methylation, Genetic Predisposition to Disease, Gene Expression Profiling
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