Association of NPSR1 gene variation and neural activity in patients with panic disorder and agoraphobia and healthy controls

Johanna Gechter; Carolin Liebscher; Maximilian J Geiger; André Wittmann; Florian Schlagenhauf; Ulrike Lueken; Hans-Ulrich Wittchen; Bettina Pfleiderer; Volker Arolt; Tilo Kircher; Benjamin Straube; Jürgen Deckert; Heike Weber; Martin J Herrmann; Andreas Reif; Katharina Domschke; Andreas Ströhle

doi:10.1016/j.nicl.2019.102029

Association of NPSR1 gene variation and neural activity in patients with panic disorder and agoraphobia and healthy controls

Neuroimage Clin. 2019:24:102029. doi: 10.1016/j.nicl.2019.102029. Epub 2019 Oct 21.

Authors

Johanna Gechter¹, Carolin Liebscher², Maximilian J Geiger³, André Wittmann², Florian Schlagenhauf², Ulrike Lueken⁴, Hans-Ulrich Wittchen⁵, Bettina Pfleiderer⁶, Volker Arolt⁷, Tilo Kircher⁸, Benjamin Straube⁸, Jürgen Deckert⁹, Heike Weber¹⁰, Martin J Herrmann⁹, Andreas Reif¹¹, Katharina Domschke¹², Andreas Ströhle²

Affiliations

¹ Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany. Electronic address: johanna.gechter@charite.de.
² Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany.
³ Epilepsy Center, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
⁴ Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany.
⁵ Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Dresden, Germany.
⁶ Department of Clinical Radiology, Medical Faculty - University of Muenster, and University Hospital Muenster, Muenster, Germany.
⁷ Department of Psychiatry, University of Münster, Münster, Germany.
⁸ Department of Psychiatry and Psychotherapy & Center for Mind, Brain and Behavior - MCMBB, Philipps-University Marburg, Marburg, Germany.
⁹ Center of Mental Health, Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Wuerzburg, Wuerzburg, Germany.
¹⁰ Center of Mental Health, Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Wuerzburg, Wuerzburg, Germany; Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University of Frankfurt, Frankfurt, Germany.
¹¹ Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University of Frankfurt, Frankfurt, Germany.
¹² Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Abstract

Introduction: The neurobiological mechanisms behind panic disorder with agoraphobia (PD/AG) are not completely explored. The functional A/T single nucleotide polymorphism (SNP) rs324981 in the neuropeptide S receptor gene (NPSR1) has repeatedly been associated with panic disorder and might partly drive function respectively dysfunction of the neural "fear network". We aimed to investigate whether the NPSR1 T risk allele was associated with malfunctioning in a fronto-limbic network during the anticipation and perception of agoraphobia-specific stimuli.

Method: 121 patients with PD/AG and 77 healthy controls (HC) underwent functional magnetic resonance imaging (fMRI) using the disorder specific "Westphal-Paradigm". It consists of neutral and agoraphobia-specific pictures, half of the pictures were cued to induce anticipatory anxiety.

Results: Risk allele carriers showed significantly higher amygdala activation during the perception of agoraphobia-specific stimuli than A/A homozygotes. A linear group x genotype interaction during the perception of agoraphobia-specific stimuli showed a strong trend towards significance. Patients with the one or two T alleles displayed the highest and HC with the A/A genotype the lowest activation in the inferior orbitofrontal cortex (iOFC).

Discussion: The study demonstrates an association of the NPSR1rs324981 genotype and the perception of agoraphobia-specific stimuli. These results support the assumption of a fronto-limbic dysfunction as an intermediate phenotype of PD/AG.

Trial registration: ClinicalTrials.gov NCT01323556.

Keywords: Agoraphobia; Imaging genetics; NPSR1; Panic disorder; Westphal-Paradigm; fMRI.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Agoraphobia / genetics*
Agoraphobia / physiopathology*
Agoraphobia / psychology
Alleles
Anticipation, Psychological
Female
Frontal Lobe / physiopathology
Genetic Variation
Genotype
Humans
Limbic System / physiopathology
Magnetic Resonance Imaging
Male
Nerve Net / physiopathology
Panic Disorder / genetics*
Panic Disorder / physiopathology*
Panic Disorder / psychology
Perception
Polymorphism, Single Nucleotide
Receptors, G-Protein-Coupled / genetics*
Risk Assessment

Substances

NPSR1 protein, human
Receptors, G-Protein-Coupled

Associated data

ClinicalTrials.gov/NCT01323556