title: Neuropeptide S receptor gene variation modulates anterior cingulate cortex Glx levels during CCK-4 induced panic.
abstract: An excitatory-inhibitory neurotransmitter dysbalance has been suggested in pathogenesis of panic disorder. The neuropeptide S (NPS) system has been implicated in modulating GABA and glutamate neurotransmission in animal models and to genetically drive altered fear circuit function and an increased risk of panic disorder in humans. Probing a multi-level imaging genetic risk model of panic, in the present magnetic resonance spectroscopy (MRS) study brain glutamate+glutamine (Glx) levels in the bilateral anterior cingulate cortex (ACC) during a pharmacological cholecystokinin tetrapeptide (CCK-4) panic challenge were assessed depending on the functional neuropeptide S receptor gene (NPSR1) rs324981 A/T variant in a final sample of 35 healthy male subjects. The subjective panic response (Panic Symptom Scale; PSS) as well as cortisol and ACTH levels were ascertained throughout the experiment. CCK-4 injection was followed by a strong panic response. A significant time×genotype interaction was detected (p=.008), with significantly lower ACC Glx/Cr levels in T allele carriers as compared to AA homozygotes 5min after injection (p=.003). CCK-4 induced significant HPA axis stimulation, but no effect of genotype was discerned. The present pilot data suggests NPSR1 gene variation to modulate Glx levels in the ACC during acute states of stress and anxiety, with blunted, i.e. possibly maladaptive ACC glutamatergic reactivity in T risk allele carriers. Our results underline the notion of a genetically driven rapid and dynamic response mechanism in the neural regulation of human anxiety and further strengthen the emerging role of the NPS system in anxiety.
authors.affiliation: Mood and Anxiety Disorders Research Unit, Department of Psychiatry and Psychotherapy, University of Muenster, Germany.
authors.forename: Tillmann
authors.initials: T
authors.lastname: Ruland
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Domschke
authors.affiliation: Mood and Anxiety Disorders Research Unit, Department of Psychiatry and Psychotherapy, University of Muenster, Germany.
authors.forename: Valerie
authors.initials: V
authors.lastname: Schütte
authors.affiliation: Mood and Anxiety Disorders Research Unit, Department of Psychiatry and Psychotherapy, University of Muenster, Germany; Department of Psychiatry and Psychotherapy, University of Marburg, Germany.
authors.forename: Maxim
authors.initials: M
authors.lastname: Zavorotnyy
authors.affiliation: Department of Clinical Radiology, University of Muenster, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Kugel
authors.affiliation: Mood and Anxiety Disorders Research Unit, Department of Psychiatry and Psychotherapy, University of Muenster, Germany.
authors.forename: Swantje
authors.initials: S
authors.lastname: Notzon
authors.affiliation: Mood and Anxiety Disorders Research Unit, Department of Psychiatry and Psychotherapy, University of Muenster, Germany.
authors.forename: Nadja
authors.initials: N
authors.lastname: Vennewald
authors.affiliation: Mood and Anxiety Disorders Research Unit, Department of Psychiatry and Psychotherapy, University of Muenster, Germany.
authors.forename: Patricia
authors.initials: P
authors.lastname: Ohrmann
authors.affiliation: Mood and Anxiety Disorders Research Unit, Department of Psychiatry and Psychotherapy, University of Muenster, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Arolt
authors.affiliation: Department of Clinical Radiology, University of Muenster, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Pfleiderer
authors.affiliation: Mood and Anxiety Disorders Research Unit, Department of Psychiatry and Psychotherapy, University of Muenster, Germany; kbo-Inn-Salzach-Klinikum, Wasserburg am Inn, Germany; Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University of Munich, Munich, Germany. Electronic address: peter.zwanzger@kbo.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Zwanzger
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D001774:Blood Chemical Analysis; D003401:Creatine / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005838:Genotype; D060005:Genotyping Techniques; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006179:Gyrus Cinguli / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D010200:Panic / Q000502:physiology*; D010865:Pilot Projects; D066244:Proton Magnetic Resonance Spectroscopy; D011569:Psychiatric Status Rating Scales; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D013758:Tetragastrin; D013997:Time Factors; D055815:Young Adult
chemical_list: C484532:NPSR1 protein, human; D043562:Receptors, G-Protein-Coupled; D013758:Tetragastrin; D005973:Glutamine; D018698:Glutamic Acid; D000324:Adrenocorticotropic Hormone; D003401:Creatine; D006854:Hydrocortisone
keywords: ACC; Glx; Imaging genetics; MRS; NPSR1