Epigenetic signature of MAOA and MAOB genes in mental disorders

Epigenetic processes such as DNA methylation are considered key mechanisms at the crossroads between genetics and environment in the etiology of mental disorders. The monoamine oxidases A and B (MAOA/MAOB) are prime candidates for the investigation into the role of DNA methylation in mental disorders, given their pivotal role in the metabolism of monoamines and as pharmacological targets of potent antidepressant drugs such as tranylcypromine, phenelzine or moclobemide. The present mini-review aims at summarizing and critically discussing the growing body of the literature supporting a role of DNA methylation of the MAOA gene promoter/exon I/intron I region and its interaction with environmental factors in several mental disorders, i.e., anxiety disorders, depression, posttraumatic stress disorder, substance use disorder, conduct disorder/antisocial personality disorder, borderline personality disorder and schizophrenia, as well as some pilot data on MAOB methylation in smokers and patients with borderline personality disorder. Furthermore, first evidence for MAOA methylation to be involved in treatment response prediction and as a potential mechanistic correlate of fear extinction is presented. Altered MAOA gene DNA methylation emerges as a possible pathogenetically relevant epigenetic mechanism in mental disorders. Given robust replication and further functional characterization, MAOA methylation patterns might serve as a peripheral biomarker of disease risk and treatment response informing preventive and personalized therapeutic approaches in the future.