There is strong evidence for a genetic contribution to the pathogenesis of
panic disorder, with a recent linkage study pointing toward a risk locus on chromosome 4q31-q34 [Kaabi et al., 2006]. Since the
neuropeptide Y (NPY) system has been reported to be involved in the pathophysiology of anxiety and in particular
panic disorder and the genes coding for NPY Y1, Y2, and Y5 receptors are located in the suggested risk region (4q31-q32), variants in the NPY, NPY Y1, Y2, and Y5 genes were investigated for association with
panic disorder in a sample of 230 German patients with
panic disorder and matched healthy controls. A synonymous (Gly-426-Gly) NPY Y5 coding variant (rs11946004) as well as haplotypes including rs11946004 and an intronic NPY Y5 variant (rs11724320) were significantly associated with
panic disorder (P = 0.027), with the effect originating from the subgroup of female patients (P = 0.030), particularly with concurrent
agoraphobia (P = 0.002-0.019). No association was observed for any variants located in the genes coding for NPY, NPY Y1, or Y2. The present results provide preliminary support for an influence of
NPY Y5 receptor variants on the etiology of
panic disorder in a potentially gender-specific manner further strengthening the evidence for a risk locus on chromosome 4q31-q34 in
anxiety disorders. However, in order to allow for conclusive evaluation of the present finding and to exclude a false positive result, further studies in larger, independent, preferably family based samples are warranted.