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Prog Neuropsychopharmacol Biol Psychiatry. 2007 Oct 1;31(7):1444-8. Epub 2007 Jul 3.

Gender-specific association of a functional coding polymorphism in the Neuropeptide S receptor gene with panic disorder but not with schizophrenia or attention-deficit/hyperactivity disorder.

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Department of Pharmacology, University of California Irvine, 360 Med Surge 2, Irvine, CA 92697, USA.


Panic disorder is a common anxiety disorder characterized by sudden and recurrent panic attacks. Previous studies have indicated significant genetic contributions and a susceptibility locus for panic disorder has been mapped to human chromosome 7p 15. The receptor for Neuropeptide S (NPS) is located in the same genomic region while NPS is known to produce arousal and anxiolytic-like effects in rodents. Here we report that a coding polymorphism in the Neuropeptide S receptor (NPSR) is associated with panic disorder in male patients of Japanese ancestry. The polymorphism (Asn(107)Ile) results in a gain-of-function of the receptor protein by increasing the agonist sensitivity about tenfold. The allele representing the less active isoform (NPSR Asn(107)) was found under-represented in male panic disorder patients, indicating a potential protective function of the protein. Two unrelated groups of patients diagnosed with schizophrenia or attention-deficit/hyperactivity disorder (ADHD) showed no association of particular NPSR alleles with the disorders. These results provide evidence for a gender-specific effect of NPSR in the pathogenesis of panic disorder.

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