title: Neuropeptide S receptor (NPSR1) gene variation modulates response inhibition and error monitoring.
abstract: The neuropeptide S (NPS) system has been suggested to contribute to the pathogenesis of anxiety. In order to further characterize the cognitive-neurophysiological relevance of neuropeptide S in the etiology of anxiety, the influence of a functional neuropeptide S receptor gene (NPSR1) variant on response inhibition and error monitoring was investigated under consideration of the dimensional phenotype of anxiety sensitivity (AS). In a sample of N=97 healthy probands, event-related potential (ERP) measurement using a modified Flanker task was applied allowing for a distinct neurophysiological examination of processes related to response inhibition (Nogo-N2, Nogo-P3) and error monitoring (Ne/ERN). All subjects were genotyped for the functional NPSR1 A/T (Asn(107)Ile) variant (rs324981) and characterized for anxiety sensitivity using the Anxiety Sensitivity Index (ASI). Carriers of the NPSR1 T allele displayed intensified response inhibition (Nogo-P3) and error monitoring (Ne/ERN), which was in both cases paralleled by the behavioral data. Furthermore, anxiety sensitivity was found to be higher in NPSR1 T allele carriers and to correlate with Nogo-P3 and Ne/ERN. A mediation analysis revealed the ERN to mediate the effect between NPSR1 genotype and anxiety sensitivity. In summary, the more active NPSR1 T allele may confer enhanced response inhibition and increased error monitoring and might drive particularly error monitoring as a neurophysiological endophenotype of anxiety as reflected by increased anxiety sensitivity. These findings further corroborate a major role of the neuropeptide S system in the pathogenesis of anxiety and suggest a potentially beneficial use of therapeutic agents targeting the NPS system in anxiety disorders.
authors: Institute for Cognitive Neuroscience, Biopsychology, Ruhr-University of Bochum, D-44780 Bochum, Germany.
authors: Christian
authors: C
authors: Beste
authors: Carsten
authors: C
authors: Konrad
authors: Christina
authors: C
authors: Uhlmann
authors: Volker
authors: V
authors: Arolt
authors: Peter
authors: P
authors: Zwanzger
authors: Katharina
authors: K
authors: Domschke
mesh_terms: D000328:Adult; D001007:Anxiety / Q000235:genetics*; D004569:Electroencephalography; D005071:Evoked Potentials / Q000502:physiology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*
chemical_list: C484532:NPSR1 protein, human; D043562:Receptors, G-Protein-Coupled