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Neuropeptide S Receptor (NPSR) Gene - Converging Evidence for a Role in Panic Disorder

Abstract : Animal studies have suggested neuropeptide S (NPS) and its receptor (NPSR) to be involved in the pathogenesis of anxiety-related behavior. In the present study, a multilevel approach was applied to further elucidate the role of NPS in the etiology of human anxiety. The functional NPSR A/T (Asn107Ile) variant (rs324981) was investigated for association with (1) panic disorder with and without agoraphobia in two large, independent case-control studies, (2) dimensional anxiety traits, (3) autonomic arousal level during a behavioral avoidance test and (4) brain activation correlates of anxiety-related emotional processing in panic disorder. The more active NPSR rs324981 T allele was found to be associated with panic disorder in the female subgroup of patients in both samples as well as in a meta-analytic approach. The T risk allele was further related to elevated anxiety sensitivity, increased heart rate and higher symptom reports during a behavioral avoidance test as well as decreased activity in the dorsolateral prefrontal, lateral orbitofrontal and anterior cingulate cortex during processing of fearful faces in patients with panic disorder. The present results provide converging evidence for a female-dominant role of NPSR gene variation in panic disorder potentially via heightened autonomic arousal and distorted processing of anxiety-relevant emotional stimuli.
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Katharina Domschke, Andreas Reif, Heike Weber, Jan Richter, Christa Hohoff, et al.. Neuropeptide S Receptor (NPSR) Gene - Converging Evidence for a Role in Panic Disorder. Molecular Psychiatry, Nature Publishing Group, 2010, ⟨10.1038/mp.2010.81⟩. ⟨hal-00552527⟩

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