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: Tillmann Ruland, Katharina Domschke, Valerie Schütte, Maxim Zavorotnyy, Harald Kugel, Swantje Notzon, Nadja Vennewald, Patricia Ohrmann, Volker Arolt, Bettina Pfleiderer, Peter Zwanzger
• Journal: European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology (Eur Neuropsychopharmacol) Vol. 25 Issue 10 Pg. 1677-82 (Oct 2015) ISSN: 1873-7862 [Electronic] Netherlands
• PMID: 26235955 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Chemical References

• NPSR1 protein, human
• Receptors, G-Protein-Coupled
• Tetragastrin
• Glutamine
• Glutamic Acid
• Adrenocorticotropic Hormone
• Creatine
• Hydrocortisone

Topics

• Adrenocorticotropic Hormone (blood)
• Adult
• Blood Chemical Analysis
• Creatine (metabolism)
• Enzyme-Linked Immunosorbent Assay
• Genotype
• Genotyping Techniques
• Glutamic Acid (metabolism)
• Glutamine (metabolism)
• Gyrus Cinguli (metabolism)
• Humans
• Hydrocortisone (blood)
• Male
• Panic (physiology)
• Pilot Projects
• Proton Magnetic Resonance Spectroscopy
• Psychiatric Status Rating Scales
• Receptors, G-Protein-Coupled (genetics)
• Tetragastrin
• Time Factors
• Young Adult