title: 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.affiliation: Department of Psychiatry, University of Münster, Münster, Germany. dannlow@uni-muenster.de
authors.forename: Udo
authors.initials: U
authors.lastname: Dannlowski
authors.forename: Harald
authors.initials: H
authors.lastname: Kugel
authors.forename: Friederike
authors.initials: F
authors.lastname: Franke
authors.forename: Anja
authors.initials: A
authors.lastname: Stuhrmann
authors.forename: Christa
authors.initials: C
authors.lastname: Hohoff
authors.forename: Peter
authors.initials: P
authors.lastname: Zwanzger
authors.forename: Thomas
authors.initials: T
authors.lastname: Lenzen
authors.forename: Dominik
authors.initials: D
authors.lastname: Grotegerd
authors.forename: Thomas
authors.initials: T
authors.lastname: Suslow
authors.forename: Volker
authors.initials: V
authors.lastname: Arolt
authors.forename: Walter
authors.initials: W
authors.lastname: Heindel
authors.forename: Katharina
authors.initials: K
authors.lastname: Domschke
mesh_terms: D000328:Adult; D000679:Amygdala / Q000502:physiology*; D001007:Anxiety / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D001008:Anxiety Disorders / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D005239:Fear / Q000502:physiology*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism
chemical_list: C484532:NPSR1 protein, human; D009479:Neuropeptides; D043562:Receptors, G-Protein-Coupled; C506531:neuropeptide S, human