title: Neuropeptide S receptor gene: fear-specific modulations of prefrontal activation.
abstract: Since central administration of neuropeptide S (NPS) has been shown to exert anxiolytic effects on rodent behavior in a number of studies, genetic variants of its cognate G-protein coupled receptor (NPSR1) became the focus of several recent human studies on anxiety and anxiety disorders. The T allele of rs324981, which goes along with enhanced receptor function, was associated with panic disorder, increased anxiety sensitivity in healthy subjects, attenuated prefrontal brain activation and elevated amygdala responses to fear-relevant stimuli. To investigate whether prefrontal attenuations in rs324981 T allele carriers are specific to fear-relevant stimulus content and cannot be attributed to a generally higher interference of emotional stimuli, 92 subjects performed a combined cognitive and emotional Stroop task while oxygenation changes in the prefrontal cortex were recorded using functional near-infrared spectroscopy. Results showed a specific NPSR1 gene activation modulation in response to fear-relevant word stimuli. Only A-homozygotes displayed an emotional Stroop effect in terms of increased activation to fear-relevant stimuli in medial and dorsolateral prefrontal cortex. Specifically, activation in the fear-relevant condition was higher in A-homozygotes as compared to T allele carriers while no group differences were found during neutral, congruent or highly interfering incongruent color word presentation. The current results are in line with earlier imaging genetic studies and suggest a potential protective function of the NPSR1 rs324981 A/A genotype against pathologically enhanced anxiety that might be explained by stronger reflective prefrontal regulation over the subcortical fear response.
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Füchsleinstrasse 15, 97080 Würzburg, Germany; Institute of Medical Psychology and Systems Neuroscience, University of Münster, Von-Esmarch-Strasse 52, 48149 Münster, Germany. Electronic address: Sara.Tupak@uni-muenster.de.
authors.forename: Sara V
authors.initials: SV
authors.lastname: Tupak
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Füchsleinstrasse 15, 97080 Würzburg, Germany. Electronic address: Reif_A@klinik.uni-wuerzburg.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Reif
authors.affiliation: Department of Psychology, University of Würzburg, Marcusstrasse 9-11, 97070 Würzburg, Germany. Electronic address: Pauli@psychologie.uni-wuerzburg.de.
authors.forename: Paul
authors.initials: P
authors.lastname: Pauli
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Füchsleinstrasse 15, 97080 Würzburg, Germany; Department of Psychiatry and Psychotherapy, University of Tübingen, Calwerstrasse 14, 72076 Tübingen, Germany. Electronic address: Thomas.Dresler@med.uni-tuebingen.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Dresler
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Füchsleinstrasse 15, 97080 Würzburg, Germany. Electronic address: Herrmann_M@klinik.uni-wuerzburg.de.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Herrmann
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Füchsleinstrasse 15, 97080 Würzburg, Germany; Department of Psychiatry and Psychotherapy, University of Münster, Albert-Schweitzer-Campus 1, 48149 Münster, Germany. Electronic address: Domschke_K@klinik.uni-wuerzburg.de.
authors.forename: Katharina
authors.initials: K
authors.lastname: Domschke
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Füchsleinstrasse 15, 97080 Würzburg, Germany.
authors.forename: Clara
authors.initials: C
authors.lastname: Jochum
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Füchsleinstrasse 15, 97080 Würzburg, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Haas
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Füchsleinstrasse 15, 97080 Würzburg, Germany; Department of Psychology, University of Würzburg, Marcusstrasse 9-11, 97070 Würzburg, Germany. Electronic address: E_Baumann_C@klinik.uni-wuerzburg.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Baumann
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Füchsleinstrasse 15, 97080 Würzburg, Germany. Electronic address: Weber_H2@klinik.uni-wuerzburg.de.
authors.forename: Heike
authors.initials: H
authors.lastname: Weber
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Tübingen, Calwerstrasse 14, 72076 Tübingen, Germany. Electronic address: Andreas.Fallgatter@med.uni-tuebingen.de.
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Fallgatter
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Füchsleinstrasse 15, 97080 Würzburg, Germany. Electronic address: Deckert_J@klinik.uni-wuerzburg.de.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Deckert
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Tübingen, Calwerstrasse 14, 72076 Tübingen, Germany. Electronic address: Ann-Christine.Ehlis@med.uni-tuebingen.de.
authors.forename: Ann-Christine
authors.initials: AC
authors.lastname: Ehlis
mesh_terms: D000328:Adult; D001007:Anxiety / Q000235:genetics*; D005239:Fear; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D017397:Prefrontal Cortex / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D019265:Spectroscopy, Near-Infrared; D057190:Stroop Test; D055815:Young Adult
chemical_list: C484532:NPSR1 protein, human; D043562:Receptors, G-Protein-Coupled
keywords: Anxiety; Emotion regulation; Fear; NIRS; NPSR; PFC