Suicide epigenetics a review of recent progressJournal of Affective Disorders
Article in review: Cheung, S., Woo, J., Maes, M. & Zai , C. (2020) Suicide epigenetics, a review of recent progress. Journal of Affective Disorders, https://doi.org/10.1016/j.jad.2020.01.040
This literature review looks at publications on the topic of suicide epigenetics, with a focus on studies that matched suicide cases with control factors such as early life adversity or diagnosis of psychotic illness. The review looked at articles that considered the epigenetics of suicide, namely changes including through the processes of DNA methylation, miRNA interference and histone modification that could lead to increased suicide risk. Several promising avenues for future investigation were identified.
Epigenetics and suicide
The strongest predictors of suicide are family history of suicide, past suicide attempts and psychiatric illness, with more than 80% of people who die by suicide having a diagnosed psychiatric illness. As we have covered in some of our recent article summaries, we are learning more about the suicide risks associated with early life adversity, childhood trauma and low socioeconomic status. These factors are often complex and interrelated.
With a family history of suicide considered a risk factor, our understanding of the relationship between suicide risk and genetics could well be improved. The increasing recognition of the role of environmental factors in suicide risk, research is underway to look at potential epigenetic markers for increased suicide risk. The most commonly studied forms of epigenetic modification in suicide are:
• DNA methylation – in which modified amino acid donates methyl to a particular genome
• MiRNA interference – a process in which tiny nucleotides interact with targets
• Histone modification – where proteins package DNA in a way that leads to variations in the relevant processes such as repair and chromosome packaging
This literature review involved the assessment of articles on suicide Epigenetics that had been published in English between 2008 and 2018 and which compared DNA methylation, miRNA interference and/or histone modification. A total of 52 articles were included in the review:
• DNA methylation – 41
• miRNA interference – 8
• Histone modification – 3
• Epigenome wide – 11
• Candidate gene studies – 29
Themes and Findings
Two important themes emerged from the review, the role of early life adversity and psychiatric disorders in the epigenetic changes noted in suicide. Epigenetic changes may be more related to early life adversity than suicide, and childhood trauma may be considered an important covariate. There were mixed results related to DNA Methylation and miRNA expression – reporting either no significant differences between suicide cases and control or different epigenetic change. Studies into specific miRNA expressions may be worth pursuing.
Of the biological processes considered in studies, those involving the neurotrophic system showed to be the most promising. A reduction in the BDNF promoter hypermethylation may be a potential marker of suicide. Three studies into this process identified a correlation between BDNF promoter hypermethylation and suicide ideation and attempt amongst different population groups, including MDD patients, and a group of women who had undergone surgery for breast cancer.
The review highlights the heterogeneity apparent across epigenetics studies in relation to suicide. Future research should seek to replicate findings from smaller studies across larger samples and across different population cohorts, including those in receipt of psychiatric care.
There is a need for a greater understanding about the clinical implications of epigenetic markers in suicide, which in turn, has huge implications for suicide risk assessment and prevention. If we can gain clues to a person’s suicide risk from their biological state, we could then identify and respond to these risks earlier.