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

Udo Dannlowski (1) , Harald Kugel (1) , Friederike Franke (1) , Anja Stuhrmann (1) , Christa Hohoff (1) , Peter Zwanzger (1) , Thomas Lenzen (1) , Dominik Grotegerd (1) , Thomas Suslow (1) , Volker Arolt (1) , Walter Heindel (1) , Katharina E Domschke (1)

1 Department of Psychiatry

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 NPS receptor 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. 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 basolateral amygdala. Furthermore, responsiveness to aversive stimuli within this basolateral amygdala cluster predicted 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. Methods: In 79 healthy subjects genotyped for NPSR rs324981, amygdala responses were assessed by means of fMRI. Participants were presented with fear-relevant faces in a robust emotion processing paradigm frequently used to study amygdala responsiveness. Results: We observed a strong association of NPSR T alleles with right amygdala responsiveness to fear-relevant faces. The association peak was located in the basolateral amygdala. Furthermore, responsiveness to aversive stimuli within this basolateral amygdala cluster predicted participant's self-reported harm avoidance but not depression level. Conclusions: 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.

Mots clés: Mood; Stress Disorders; Imaging; Clinical or Preclinical; Neuropeptides; Neurogenetics; Neuropeptide S; Emotion; Amygdala; Anxiety; fMRI

Udo Dannlowski, Harald Kugel, Friederike Franke, Anja Stuhrmann, Christa Hohoff, et al.. Neuropeptide S (NPS) receptor genotype modulates basolateral amygdala responsiveness to aversive stimuli. Neuropsychopharmacology, 2011, ⟨10.1038/npp.2011.73⟩. ⟨hal-00636195⟩