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

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

Author information

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.

KEYWORDS:

Agoraphobia; Imaging genetics; NPSR1; Panic disorder; Westphal-Paradigm; fMRI

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