Effect of MAOA DNA methylation on human in vivo protein expression measured by harmine PET in healthy and depressed individuals

Epigenetic modifications, such as DNA methylation, are understood as an intermediary between environmental factors affecting disease risk and pathophysiologic changes to brain structure and function. Cerebral monoamine oxidase A (MAO-A) levels are altered in depression, as are DNA methylation levels within the MAOA gene, particularly in the promoter / exon I / intron I region. An effect of MAOA methylation on peripheral protein expression was shown, but the extent to which methylation affects brain MAO-A levels is not fully understood. Here, the influence of average and CpG site-specific MAOA promoter / exon I / intron I region DNA methylation on global MAO-A distribution volume (VT), an index of MAO-A density, was assessed via [11C]harmine positron emission tomography in 22 patients suffering from winter-type seasonal affective disorder and 30 healthy controls. No significant influence of MAOA DNA methylation on global MAO-A VT was found, despite correction for health status (patients vs. controls), sex, season (methylation analysis in spring / summer vs. fall / winter) and MAOA variable number of tandem repeat genotype (VNTR; high vs. low expression groups). However, in female subjects, season affected average DNA methylation, with higher levels in spring and summer (puncorr = 0.03). We thus did not find evidence for an effect of MAOA DNA methylation on brain MAO-A VT. In contrast to a previous study that demonstrated an effect of the methylation of a MAOA promoter region located further 5 on brain MAO-A, in the present study MAOA methylation appears to affect brain protein levels to a limited extent. The observed effect of season on methylation levels is in accordance with extensive evidence for seasonal effects within the serotonergic system. Clinicaltrials.gov IdentifierNCT02582398 EUDAMED NumberCIV-AT-13-01-009583