Neuropeptide-S (NPS) receptor genotype modulates basolateral amygdala responsiveness to aversive stimuli.

Abstract

Recent studies point to a role of neuropeptide-S (NPS) in the etiology of anxiety disorders. In animal models, NPS and its receptor (NPSR) were shown to be highly expressed in the amygdala, a central structure in the fear circuit, also known to be hyper-responsive in anxiety disorders. Recently, a functional polymorphism in the NPSR gene (rs324981 A/T) has been associated with panic disorder and anxiety sensitivity. However, the role of NPSR gene variation in the modulation of fear-related amygdala responsiveness remains to be clarified. In 79 healthy subjects genotyped for NPSR rs324981, amygdala responses were assessed by means of fMRI. The participants were presented with fear-relevant faces in a robust emotion-processing paradigm frequently used to study amygdala responsiveness. We observed a strong association of NPSR T-alleles with right amygdala responsiveness to fear-relevant faces. The association peak was located in the BLA. Furthermore, responsiveness to aversive stimuli within this BLA cluster predicted a participant's self-reported harm avoidance but not depression level. We conclude that NPSR genotype is associated with increased amygdala responsiveness to fear-relevant stimuli. Thereby, NPSR rs324981 apparently causes an indirect effect on anxiety-related traits and potentially contributes to the pathogenesis of anxiety disorders by shaping fear-related limbic activity.

• Authors: Udo Dannlowski, Harald Kugel, Friederike Franke, Anja Stuhrmann, Christa Hohoff, Peter Zwanzger, Thomas Lenzen, Dominik Grotegerd, Thomas Suslow, Volker Arolt, Walter Heindel, Katharina Domschke
• Journal: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology (Neuropsychopharmacology) Vol. 36 Issue 9 Pg. 1879-85 (Aug 2011) ISSN: 1740-634X [Electronic] England
• PMID: 21525857 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• NPSR1 protein, human
• Neuropeptides
• Receptors, G-Protein-Coupled
• neuropeptide S, human

Topics

• Adult
• Amygdala (physiology)
• Anxiety (genetics, metabolism, physiopathology)
• Anxiety Disorders (genetics, metabolism, physiopathology)
• Fear (physiology)
• Female
• Genetic Predisposition to Disease (genetics)
• Genotype
• Humans
• Male
• Middle Aged
• Neuropeptides (genetics, metabolism)
• Receptors, G-Protein-Coupled (genetics, metabolism)