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Neuropeptide S receptor gene — converging evidence for a role in panic disorder

Molecular Psychiatry volume 16, pages 938–948 (2011)Cite this article

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Abstract

Animal studies have suggested neuropeptide S (NPS) and its receptor (NPSR) to be involved in the pathogenesis of anxiety-related behavior. In this study, a multilevel approach was applied to further elucidate the role of NPS in the etiology of human anxiety. The functional NPSR A/T (Asn107Ile) variant (rs324981) was investigated for association with (1) panic disorder with and without agoraphobia in two large, independent case–control studies, (2) dimensional anxiety traits, (3) autonomic arousal level during a behavioral avoidance test and (4) brain activation correlates of anxiety-related emotional processing in panic disorder. The more active NPSR rs324981 T allele was found to be associated with panic disorder in the female subgroup of patients in both samples as well as in a meta-analytic approach. The T risk allele was further related to elevated anxiety sensitivity, increased heart rate and higher symptom reports during a behavioral avoidance test as well as decreased activity in the dorsolateral prefrontal, lateral orbitofrontal and anterior cingulate cortex during processing of fearful faces in patients with panic disorder. The present results provide converging evidence for a female-dominant role of NPSR gene variation in panic disorder potentially through heightened autonomic arousal and distorted processing of anxiety-relevant emotional stimuli.

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Acknowledgements

This study was supported by the Deutsche Forschungsgemeinschaft (DFG; SFB-TRR-58 projects C2 and Z2 to KD, AR, PP and JD; Grant KFO 125 to AR; DE357/4-1 to AR, AH and JD; RE1632/5 to AR) and the BMBF (Panic-Net, to ALG, TK, AS, HUW, VA, AH and JD; details see web page http://www.paniknetz.de/netzwerk.html). The recruitment of the Max Planck panic sample in Munich was supported by the Max Planck Excellence Foundation. We gratefully acknowledge the skilful technical support by Anna Baffa.

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  1. K Domschke and A Reif: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Psychiatry, University of Muenster, Muenster, Germany

    K Domschke, C Hohoff, P Ohrmann, A Pedersen, J Bauer, T Suslow, B Klauke, M Rothermundt & V Arolt

  2. Department of Psychiatry, University of Wuerzburg, Wuerzburg, Germany

    A Reif, H Weber, C Baumann, C Jacob & J Deckert

  3. Institute of Psychology, University of Greifswald, Greifswald, Germany

    J Richter & A Hamm

  4. Institute of Psychology, University of Muenster, Muenster, Germany

    A Pedersen & A L Gerlach

  5. Department of Radiology, University of Muenster, Muenster, Germany

    H Kugel & W Heindel

  6. Department of Psychiatry, University of Bonn, Bonn, Germany

    W Maier

  7. Department of Psychiatry, University of Frankfurt, Frankfurt, Germany

    J Fritze

  8. Department of Psychiatry, University of Goettingen, Goettingen, Germany

    B Bandelow

  9. Institute of Transfusion Medicine and Transplantation Immunology, University of Muenster, Muenster, Germany

    P Krakowitzky

  10. Max-Planck-Institute of Psychiatry, Munich, Germany

    A Erhardt, E B Binder & F Holsboer

  11. Institute of Clinical Psychology and Psychotherapy, University of Koeln, Koeln, Germany

    A L Gerlach

  12. Department of Psychiatry, University of Marburg, Marburg, Germany

    T Kircher

  13. Christoph-Dornier-Foundation for Clinical Psychology, Bremen, Germany

    T Lang

  14. Zentrum für Klinische Psychologie und Rehabilitation, University of Bremen, Bremen, Germany

    T Lang

  15. Department of Psychology, University of Wuerzburg, Wuerzburg, Germany

    G W Alpers & P Pauli

  16. Department of Psychology, University of Mannheim, Mannheim, Germany

    G W Alpers

  17. Department of Psychiatry, Charité, Berlin, Germany

    A Ströhle

  18. Institute of Psychology, University of Berlin, Berlin, Germany

    L Fehm

  19. Institute of Clinical Psychology and Psychotherapy, Technical University of Dresden, Dresden, Germany

    A T Gloster & H-U Wittchen

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  1. K Domschke
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Correspondence to K Domschke.

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Domschke, K., Reif, A., Weber, H. et al. Neuropeptide S receptor gene — converging evidence for a role in panic disorder. Mol Psychiatry 16, 938–948 (2011). https://doi.org/10.1038/mp.2010.81

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