Excess of high activity monoamine oxidase A gene promoter alleles in female patients with panic disorder

A genetic contribution to the pathogenesis of panic disorder has been demon strated by clinical genetic studies. Molecular genetic studies have focused on candidate genes suggested by the molecular mechanisms implied in the ac tion of drugs utilized for therapy or in challenge tests. One class of drug s effective in the treatment of panic disorder is represented by monoamine oxidase A inhibitors. Therefore, the monoamine oxidase A gene on chromosome X is a prime candidate gene, In the present study we investigated a novel repeat polymorphism in the promoter of the monoamine oxidase A gene for ass ociation with panic disorder in two independent samples (German sample, n = 80; Italian sample, n=129). Two alleles (3 and 4 repeats) were most common and constituted >97% of the observed alleles, Functional characterization in a luciferase assay demonstrated that the longer alleles (3a, 4 and 5) we re more active than allele 3, Among females of both the German and the Ital ian samples of panic disorder patients (combined, n = 209) the longer allel es (3a, 4 and 5) were significantly more frequent than among females of the corresponding control samples (combined, n = 190, chi(2) = 10.27, df = 1, P = 0.001), Together with the observation that inhibition of monoamine oxid ase A is clinically effective in the treatment of panic disorder these find ings suggest that increased monoamine oxidase A activity is a risk factor f or panic disorder in female patients.