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Modification of caffeine effects on the affect-modulated startle by neuropeptide S receptor gene variation

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Abstract

Rationale/objectives

Both the neuropeptide S (NPS) system and antagonism at the adenosine A2A receptor (e.g., by caffeine) were found to play a crucial role in the mediation of arousal and anxiety/panic in animal and human studies. Furthermore, a complex interaction of the neuropeptide S and the adenosinergic system has been suggested with administration of the adenosine A2A receptor antagonist caffeine downregulating NPS levels (Lage et al., 2006) and attenuating the stimulatory effects of NPS in rodents (Boeck et al., 2010).

Methods

Thus, in the present study, the impact of the functional neuropeptide S receptor (NPSR) A/T (Asn107Ile; rs324981) variant on affect-modulated (neutral, unpleasant, and pleasant IAPS pictures) startle response depending on the administration of 300 mg caffeine citrate was investigated in a sample of 124 (m = 58, f = 66) healthy probands using a double-blind, placebo-controlled design.

Results

ANOVA revealed a significant interaction between NPSR genotype, challenge condition, and picture valence. Comparing startle magnitudes upon stimulation with neutral or emotional pictures between the placebo and caffeine condition, in AA/AT non-risk genotype carriers no significant difference was discerned, while TT risk genotype carriers showed a significantly increased startle magnitude in response to neutral stimuli (p = .02) and a significantly decreased startle magnitude in response to unpleasant stimuli (p = .02) in the caffeine condition as compared to the placebo condition.

Conclusions

In summary, the present findings — extending previous evidence from rodent studies — for the first time provide support for a complex, non-linear interaction of the neuropeptide S and adenosinergic systems affecting the affect-modulated startle response as an intermediate phenotype of anxiety in humans.

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Acknowledgements

This study was supported by grants from Deutsche Forschungsgemeinschaft (SFB-TRR-58 project B1 to PP and AM, C2 to KD and JD, project C1 to PZ, and project Z2 to JD, AR and PP). We gratefully acknowledge the skillful technical support by Max Hilscher, Heike Ewald, Thilo Rattay, and Julian Conrad. All authors had full control of all primary data and they agree to allow the journal to review their data if requested. The experiments comply with the current laws of the country in which they were performed.

Conflict of interest

All authors have no conflicts of interest to declare, financial or otherwise, that may have a direct bearing on the subject matter of this article.

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Authors and Affiliations

  1. Department of Psychiatry and Psychotherapy, University of Muenster, Albert-Schweitzer-Campus 1, Gebaeude A9, 48149, Muenster, Germany

    Katharina Domschke, Benedikt Klauke, Bernward Winter, Katherina Wosnitza, Andrea Dlugos, Swantje Naunin, Kathrin Nienhaus, Volker Arolt & Peter Zwanzger

  2. Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Fuechsleinstrasse 15, 97080, Wuerzburg, Germany

    Katharina Domschke, Agnes Gajewska, Martin J. Herrmann, Bodo Warrings, Christian Jacob, Andreas Reif & Jürgen Deckert

  3. Christoph-Dornier-Klinik for Psychotherapy, Tibusstrasse 7-11, 48143, Muenster, Germany

    Benedikt Klauke

  4. Department of Psychology I, University of Wuerzburg, Marcusstrasse 9-11, 97070, Wuerzburg, Germany

    Andreas Mühlberger & Paul Pauli

  5. Center for Laboratory Medicine, University of Muenster, Albert-Schweitzer-Campus 1, 48149, Muenster, Germany

    Manfred Fobker

Authors
  1. Katharina Domschke
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  2. Benedikt Klauke
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Correspondence to Katharina Domschke.

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Katharina Domschke and Benedikt Klauke contributed equally to this work and therefore both considered as first authors.

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Domschke, K., Klauke, B., Winter, B. et al. Modification of caffeine effects on the affect-modulated startle by neuropeptide S receptor gene variation. Psychopharmacology 222, 533–541 (2012). https://doi.org/10.1007/s00213-012-2678-0

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