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Multilevel impact of the dopamine system on the emotion-potentiated startle reflex

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Abstract

Rationale/objectives

The pathogenetic mechanism of emotion-related disorders such as anxiety disorders is considered to be complex with an interaction of genetic, biochemical, and environmental factors. Particular evidence has accumulated for alterations in the dopaminergic system—partly conferred by catechol-O-methyltransferase (COMT) gene variation—and for distorted emotional processing to constitute risk factors for anxiety and anxiety-related disorders.

Methods

Applying a multilevel approach, we analyzed the main and interactive effects of the functional COMT val158met polymorphism and l-dopa (single-dose 50 mg levodopa and 12.5 mg carbidopa; double-blind, placebo-controlled design) on the emotion-potentiated (unpleasant, neutral, and pleasant IAPS pictures) startle response as an intermediate phenotype of anxiety in a sample of 100 healthy probands (f = 52, m = 48).

Results

The COMT 158val allele was associated with an increased startle potentiation by unpleasant stimuli as compared with neutral stimuli irrespective of l-dopa or placebo intervention. COMT 158met/met genotype carriers, while displaying no difference in startle magnitude in response to unpleasant or neutral pictures in the placebo condition, showed startle potentiation by unpleasant pictures under l-dopa administration only.

Conclusions

The present proof-of-concept study provides preliminary support for a complex, multilevel impact of the dopaminergic system on the emotion-potentiated startle reflex suggesting increased phasic dopamine transmission driven by the more active COMT 158val allele and/or a single dose of l-dopa to predispose to maladaptive emotional processing and thereby potentially also to anxiety-related psychopathological states.

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Notes

  1. Unpleasant IAPS pictures: 3000, 3053, 3170, 3102, 9410, 3080, 6313, 3120, 3130, 3071, 3100, 3010, 3060, 3064, 3140, 3110, 3150, 9300, 2800, 3030, 6540, 9252, 9250, and 9040; neutral IAPS pictures: 2200, 2880, 5510, 5531, 7002, 7004, 7006, 7009, 7010, 7025, 7034, 7050, 7080, 7090, 7100, 7130, 7175, 7185, 7217, 7224, 7950, 2215, 5535, and 7031; pleasant IAPS pictures: 1710, 2091, 2160, 2216, 2340, 2345, 4608, 4626, 4641, 8120, 5623, 5831, 5833, 8041, 8370, 8200, 8210, 8461, 8496, and 5814; for men: 4220, 4290, 4607, and 4680; and for women: 4550, 4658, 4687, and 5631.

  2. Four additional subjects had to be excluded from this analysis because of missing results of the Anxiety Sensitivity Index.

  3. Nineteen additional subjects had to be excluded from this analysis because of consecutive zero responses leading to a missing mean in one of the four blocks (see “Methods”).

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Acknowledgments

The study was supported by grants of the Deutsche Forschungsgemeinschaft (DFG; German Research Foundation; Collaborative Research Centre “Fear, Anxiety, Anxiety Disorders” SFB-TRR-58) project C2 to KD and JD, project Z2 to JD, AR, and PP, project B1 to PP and AM and project C1 to PZ. Experiments comply with the current laws in Germany (EudraCT number 2008-001877-13). All authors had full control of all primary data and they agree to allow the journal to review their data if requested. We gratefully acknowledge the skillful technical support by Max Hilscher.

Declaration 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 the article. This is to indicate that Katharina Domschke and Bernward Winter contributed equally to this work and therefore should both be considered first authors.

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Authors and Affiliations

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

    Katharina Domschke, Agnieszka Gajewska, Stefan Unterecker, Bodo Warrings, Falko Markulin, Christian Jacob, Martin J. Herrmann, Andreas Reif & Jürgen Deckert

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

    Bernward Winter, Andrea Dlugos, Swantje Notzon, Kathrin Nienhaus, Astrid Gieselmann, Volker Arolt & Peter Zwanzger

  3. Catholic University of Applied Sciences North Rhine-Westphalia, Piusallee 89, 48147, Muenster, Germany

    Bernward Winter

  4. Institute of Psychology, University of Regensburg, Universitaetsstrasse 31, 93053, Regensburg, Germany

    Andreas Mühlberger

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

    Paul Pauli

  6. kbo-Inn-Salzach-Klinikum, 83512, Wasserburg am Inn, Germany

    Peter Zwanzger

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  1. Katharina Domschke
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Correspondence to Katharina Domschke.

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Katharina Domschke and Bernward Winter contributed equally to this work.

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Domschke, K., Winter, B., Gajewska, A. et al. Multilevel impact of the dopamine system on the emotion-potentiated startle reflex. Psychopharmacology 232, 1983–1993 (2015). https://doi.org/10.1007/s00213-014-3830-9

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