Epigenetics in psychiatry: Beyond DNA methylation

Abstract

The global burden of psychopathologies appears to be underestimated, since the global psychiatric disorder burden is exceeding other medical burdens. To be able to address this problem more effectively, we need to better understand the etiology of psychiatric disorders. One of the hallmarks of psychiatric disorders appears to be epigenetic dysregulation. While some epigenetic modifications (such as DNA methylation) are well known and studied, the roles of others have been investigated much less. DNA hydroxymethylation is a rarely studied epigenetic modification, which as well as being an intermediate stage in the DNA demethylation cycle is also an independent steady cell state involved in neurodevelopment and plasticity. In contrast to DNA methylation, DNA hydroxymethylation appears to be related to an increase in gene expression and subsequent protein expression. Although no particular gene or genetic locus can be at this point linked to changes in DNA hydroxymethylation in psychiatric disorders, the epigenetic marks present good potential for biomarker identification because the epigenetic landscape is a result of the interplay between genes and environment, which both influence the development of psychiatric disorders, and because hydoxymethylation changes are particularly enriched in the brain and in synapse-related genes.

Epigenetic Regulation in Schizophrenia: Focus on Methylation and Histone Modifications in Human Studies

“…The characterization of the presence of 5mC or 5hmC has been reported to be quite challenging since conventional bisulfite sequencing is unable to discriminate between these forms of modified cytosine [ 27 ]. For the majority of the studies a lower density of methylated CpG sites in the tested gene and/or the full genome in schizophrenia patients was noted compared to their respective control groups [ 28 , 29 , 30 ]. Interestingly, differential global hydroxymethylation levels were also found increased in male SZ patients, but decreased levels were found in female SZ patients compared to their respective controls [ 31 ].…”

Potential Inflammatory Biomarkers for Major Depressive Disorder Related to Suicidal Behaviors: A Systematic Review

“…Suicidal incidents frequently occur suddenly in situations of severe distress and are commonly triggered by factors like economic instability, relational discord, chronic pain, or medical disorders. The annual toll exceeds 700,000 fatalities from suicide, and a significantly larger population involved in suicide attempts [ 1 , 3 ]. In the face of such adversity, the endeavor to clinically anticipate the imminent risk of suicide has proven complex.…”