The monoamine oxidase A (MAOA) gene has been suggested as a prime candidate in 
the pathogenesis of panic disorder. In the present study, DNA methylation 
patterns in the MAOA regulatory and exon 1/intron 1 region were investigated for 
association with panic disorder with particular attention to possible effects of 
gender and environmental factors. Sixty-five patients with panic disorder (44 
females, 21 males) and 65 healthy controls were analysed for DNA methylation 
status at 42 MAOA CpG sites via direct sequencing of sodium bisulfate treated 
DNA extracted from blood cells. The occurrence of recent positive and negative 
life events was ascertained. Male subjects showed no or only very minor 
methylation with some evidence for relative hypomethylation at one CpG site in 
intron 1 in patients compared to controls. Female patients exhibited 
significantly lower methylation than healthy controls at 10 MAOA CpG sites in 
the promoter as well as in exon/intron 1, with significance surviving correction 
for multiple testing at four CpG sites (p≤0.001). Furthermore, in female 
subjects the occurrence of negative life events was associated with relatively 
decreased methylation, while positive life events were associated with increased 
methylation. The present pilot data suggest a potential role of MAOA gene 
hypomethylation in the pathogenesis of panic disorder particularly in female 
patients, possibly mediating a detrimental influence of negative life events. 
Future studies are warranted to replicate the present finding in independent 
samples, preferably in a longitudinal design.