Suicide results from interactions between biological, developmental, and social risk factors and it is thought that these factors will act on brain processes mediating the final outcome.Alterations in DNA methylation is considered as a key neurobiological process in suicide. DNA methylation is dynamic and responsive to external cues and signals.(=“genome adaptation” mechanism).DNA methylation is a major regulator of gene expression.Methylation of promoter area will change the expression of the gene. (Promoters are regulatory DNA sequences adjacent to the start site of a gene, regulating its expression). DNA methylation in promoter sequences is often associated with a repressive chromatin state and lower gene expression activity.Previous research has shown hypermethylation (site specific) , independent of psychopathology, in brain regions in suicide victims.
Labonté et al report the results from a genome- wide screening of promoter DNA methylation modifications found in the hippocampus of suicide completers compared with nonpsychiatric sudden-death comparison subjects.Brain samples (Quebec Suicide Brain Bank) from the left hemisphere (dentate gyrus) were obtained from 62 subjects (46 suicide completers and 16 nonpsychiatric sudden-death comparison subjects .Methylated DNA was extracted from each sample following methylated DNA immunoprecipitation.
There were no significant differences between groups in age, pH, and postmortem interval.Promoter DNA methylation levels were significantly greater for several genes in suicide completers relative to comparison subjects .Hippocampal DNA from suicide completers showed DNA methylation changes at more than 300 gene loci. This group of altered gene promoters were mainly genes implicated in cognition, learning,memory and synaptic transmission. Both hyper- and hypo methylation found in gene promoters across the genome.
In the accompanying editorial Akbarian and Halene highlight the implications of these findings.Epigenetic alterations are expected to increase vulnerability to suicide by interfering with normal gene expression patterns, leading to neurobiological abnormalities associated with the development of specific emotional and behavioral phenotypes and deregulation of cognitive processes, finally leading to suicide. As many neuronal gene promoters are epigenetically dysregulated, this area would be of interest for future drug development.
Summary of the article:
Genome-wide methylation changes in the brains of suicide completers.Labonté B, Suderman M, Maussion G, Lopez JP, Navarro-Sánchez L, Yerko V, Mechawar N, Szyf M, Meaney MJ, Turecki G. Am J Psychiatry. 2013 May 1;170(5):511-20