Epigenetics and suicidal behaviour
Abstract
Suicide is a well-defined public health problem. Slovenia is ranked as one of the European leading countries regarding suicide rate. So far, many neurotransmitter systems have been studied on genetic and biochemical levels. In recent years, focus shifted towards research in the field of epigenetics, which includes noncoding RNA (miRNA), DNA methylation, and post-translational histone modification. miRNAs are short, 19 to 25 nucleotides long single-stranded RNA molecules that bind specifically to mRNA and decrease the expression of targeted genes. Suicide victims showed changes in the expression of miRNA associated with brain neurotrophic factor (BDNF) and its receptor (TrkB), transcription and growth factors, and the polyamine system. DNA methylation is the process of adding methyl group to the 5C site of the cytosine and it results in a decrease of gene transcription. Studies of global methylation identified changes in the patterns of promoter methylation in suicide victims. Many promoters belonged to genes involved in cognitive functions. Looking at candidate genes, changes in methylation pattern were observed at genes for BDNF, TrkB, ribosomal RNA, and the type 2A serotonin receptor promoter region. Histones are the core building blocks of chromatin, representing the protein base around which the DNA is coiled and forming nucleosomes. Histones consist of a globular core part and an N-terminal tail of different lengths, which can be post-translationally modified. Most common modifications are lysine and arginine acetylation and methylation, serine and threonine phosphorylation, lysine ubiquitination and sumoylation, and ADP-ribosylation. Histone modifications of TrkB and polyamine system were observed in suicide victims. Numerous studies thus link epigenetic mechanisms to suicidal behaviour.
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References
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