The monoamine oxidase A (MAO-A) gene has been suggested as a vulnerability gene in the pathogenesis of panic disorder.

Epigenetic processes such as methylation critically influencing gene regulation and mediating adaptation to environmental factors have so far not been investigated in panic disorder.

Thus, in the present study DNA methylation patterns in the MAO-A regulatory and exon1/intron1 region were investigated for association with panic disorder.

Sixty-five patients with panic disorder (m=21, f=44) and 65 healthy controls were analyzed for DNA methylation status at 42 MAO-A CpG sites via direct sequencing of sodium bisulfate treated DNA extracted from blood cells. The occurrence of positive and negative life events was ascertained. All subjects were genotyped for the MAO-A VNTR.

Male subjects showed no or only very minor methylation. In female patients, significantly lower methylation was observed at ten MAO-A CpG sites in the promoter and exon/intron 1 in comparison to healthy controls. Additionally, in female subjects the occurrence of negative life events was associated with a decreased methylation status, while positive life events were associated with relatively increased methylation. Age, smoking status or medication did not influence methylation status, the more active MAO-A VNTR alleles were associated with increased methylation in controls.

The present study suggests a potentially female-specific role of epigenetic alterations, i.e. MAO-A gene hypomethylation, in interaction with environmental factors in the pathogenesis of panic disorder. Future studies are warranted to replicate the present finding in independent samples, preferably in a longitudinal design.