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Soc Cogn Affect Neurosci. 2015 Dec;10(12):1730-7. doi: 10.1093/scan/nsv061. Epub 2015 May 13.

Neuropeptide S receptor gene variation and neural correlates of cognitive emotion regulation.

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Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany,
Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.
Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany, LEAD Graduate School, University of Tübingen, Tübingen, Germany and.
Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt am Main, Germany.


The neuropeptide S (NPS) and its receptor NPSR have captured attention in the pathogenesis of anxiety disorders. Here, a functional polymorphism in the NPSR1 gene has been linked to deviant cortico-limbic interactions in response to negative stimuli. While healthy T allele carriers exhibited increased amygdala and prefrontal cortex activity, panic disorder patients carrying the T risk allele displayed hypofrontality possibly reflecting insufficient prefrontal inhibition of limbic reactivity. In order to study multi-level effects of genotype and anxiety, prefrontal cortex activity during an emotional n-back task was measured in 66 volunteers genotyped for the NPSR1 rs324981 A/T variant (AA homozygotes vs. T allele carriers) by means of functional near-infrared spectroscopy. For a high working memory load (3-back), T allele carriers showed a signal increase to negative pictures in the dorsolateral and medial prefrontal cortex while AA homozygotes displayed a signal decrease. Since groups did not differ on skin conductance level and behavioral parameters, this effect in the risk group in line with results from fMRI studies is speculated to represent an adaptive mechanism to compensate for presumably increased subcortical activity driven by an overactive NPS system. However, anxiety sensitivity correlated negatively with prefrontal activity in T allele carriers possibly suggesting a decompensation of the adaptive compensatory upregulation.


NPSR1; anxiety; emotional working memory; fNIRS; neuropeptide S

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