Epigenetics applied to psychiatry: Clinical opportunities and future challenges

Abstract

Psychiatric disorders are clinically heterogeneous and debilitating chronic diseases resulting from a complex interplay between gene variants and environmental factors. Epigenetic processes, such as DNA methylation and histone posttranslational modifications, instruct the cell/tissue to correctly interpret external signals and adjust its functions accordingly. Given that epigenetic modifications are sensitive to environment, stable, and reversible, epigenetic studies in psychiatry could represent a promising approach to better understanding and treating disease. In the present review, we aim to discuss the clinical opportunities and challenges arising from the epigenetic research in psychiatry. Using selected examples, we first recapitulate key findings supporting the role of adverse life events, alone or in combination with genetic risk, in epigenetic programming of neuropsychiatric systems. Epigenetic studies further report encouraging findings about the use of methylation changes as diagnostic markers of disease phenotype and predictive tools of progression and response to treatment. Then we discuss the potential of using targeted epigenetic pharmacotherapy, combined with psychosocial interventions, for future personalized medicine for patients. Finally, we review the methodological limitations that could hinder interpretation of epigenetic data in psychiatry. They mainly arise from heterogeneity at the individual and tissue level and require future strategies in order to reinforce the biological relevance of epigenetic data and its translational use in psychiatry. Overall, we suggest that epigenetics could provide new insights into a more comprehensive interpretation of mental illness and might eventually improve the nosology, treatment, and prevention of psychiatric disorders.

Above genes: epigenetics and psychiatry

“…Genes, for example, may account for 70-80% of the risk of developing schizophrenia and bipolar depression, between 48% and 75% of the likelihood of suffering major depression and 30-70% of PTSD risk. 1,2 Many genes linked to mental illnesses seem to modulate sensitivity and responses to environmental factors. 2 But genes tell only part of the story.…”

“…1,2 Many genes linked to mental illnesses seem to modulate sensitivity and responses to environmental factors. 2 But genes tell only part of the story. Biologists increasingly recognise the importance of epigenetics, which literally means 'on top of the genes', in determining the risk of developing psychiatric and other diseases as well as in the maintenance of our health and wellbeing.…”

“…Epigenetics refers to alterations in gene expression that do not involve changes to the DNA sequence, but that are transmitted through cell division and, in some cases, may be passed to the next generation. [1][2][3] Fundamentally, these epigenetic processes 'instruct the cell/tissue to correctly interpret external signals and adjust its functions accordingly'. 2 Studies of epigenetics help us understand the complex, complicated and enigmatic nature of psychiatric disease, which, in turn, raises the prospect of innovative new approaches to diagnosis, treatment and prevention.…”

“…[1][2][3] Fundamentally, these epigenetic processes 'instruct the cell/tissue to correctly interpret external signals and adjust its functions accordingly'. 2 Studies of epigenetics help us understand the complex, complicated and enigmatic nature of psychiatric disease, which, in turn, raises the prospect of innovative new approaches to diagnosis, treatment and prevention. 2,4 Epigenetic mechanisms Human DNA is around two meters long, but the nucleus is only around six microns across.…”

“…2 Studies of epigenetics help us understand the complex, complicated and enigmatic nature of psychiatric disease, which, in turn, raises the prospect of innovative new approaches to diagnosis, treatment and prevention. 2,4 Epigenetic mechanisms Human DNA is around two meters long, but the nucleus is only around six microns across. So, DNA is compacted around 10 000 times, in part by sections of 147 base pairs of DNA wrapping about 1.7 times around a core of eight histone proteins (an octamer) -an arrangement called chromatin.…”