Effect of MAOA DNA Methylation on Human in Vivo Protein Expression Measured by [(11)C]harmine Positron Emission Tomography

BACKGROUND: Epigenetic modifications like DNA methylation are understood as an intermediary between environmental factors and neurobiology. 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. METHODS: Here, the influence of MAOA promoter/exon I/intron I region DNA methylation on global MAO-A distribution volume (V(T)), an index of MAO-A density, was assessed via [(11)C]harmine positron emission tomography in 22 patients (14 females) suffering from seasonal affective disorder and 30 healthy controls (17 females). RESULTS: No significant influence of MAOA DNA methylation on global MAO-A V(T) was found, despite correction for health status, sex, season, and MAOA variable number of tandem repeat genotype. However, season affected average methylation in women, with higher levels in spring and summer (P(uncorr) = .03). We thus did not find evidence for an effect of MAOA DNA methylation on brain MAO-A V(T). CONCLUSIONS: In contrast to a previous study demonstrating an effect of methylation of a MAOA promoter region located further 5’ on brain MAO-A, MAOA methylation of the region assessed here appears to affect brain protein levels to a limited extent at most. The observed effect of season on methylation levels is in accordance with extensive evidence for seasonal effects within the serotonergic system. CLINICALTRIALS.GOV IDENTIFIER: NCT02582398 (https://clinicaltrials.gov/ct2/show/NCT02582398).