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Central serotonin transporter levels are associated with stress hormone response and anxiety

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Abstract

Rationale

Negative mood states are characterized by both stress hormone dysregulation and serotonergic dysfunction, reflected by altered thalamic serotonin transporter (5-HTT) levels. However, so far, no study examined the individual association between cortisol response and cerebral in vivo 5-HTT levels in patients suffering from negative mood states.

Objective

The objective of this cross-sectional study was to assess the interrelation of cortisol response, thalamic 5-HTT levels, and anxiety in healthy subjects and two previously published samples of patients with unipolar major depression (UMD) and obsessive–compulsive disorder (OCD), controlling for age, gender, 5-HTT genotype, smoking, and seasonality.

Methods

Regional 5-HTT levels and cortisol response to dexamethasone-corticotropin (Dex-CRH) challenge were assessed in consecutive samples of medication-free patients suffering from UMD (N = 10) and OCD (N = 10), and 20 healthy volunteers. The intervention used was combined Dex-CRH test and [11C]DASB positron emission tomography. The main outcome measures were: 5-HTT binding potential (BPND) in a predefined thalamic ROI, cortisol response defined as the maximum cortisol increase in the combined Dex-CRH-test, and state of anxiety from the state-trait-anxiety inventory.

Results

Reduced thalamic 5-HTT BPND was associated with increased cortisol response (r = −0.35, p < 0.05; in patients: r = −0.53, p < 0.01) and with increased state anxiety (r = −0.46, p < 0.01), surviving correction for age, gender, 5-HTT genotype, smoking, and seasonality (p < 0.05). The 5-HTT genotype, on the contrary, was not significantly associated with cortisol response (p = 0.19) or negative mood (p = 0.23).

Conclusion

The association between stress hormone response, thalamic 5-HTT levels, and anxiety in patients suffering from negative mood states suggests an interaction between two major mechanisms implicated in negative mood states in humans.

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Acknowledgments

The study was supported by grants from the Deutsche Forschungsgemeinschaft (He 2597/7-3, Sm 80/2-2, and Re 1472/6-2) and supported in part by the German Ministry for Education and Research (01GS08159), and the National Genome Research Network (NGFN 01GS08148). We would like to thank Professors Florian Holsboer and Jeff Meyer for their helpful comments on an earlier version of this manuscript.

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Authors and Affiliations

  1. Departments of Nuclear Medicine, PET Center and Radiopharmacy, University of Tübingen, Tübingen, Germany

    Matthias Reimold, Hans-Jürgen Machulla & Roland Bares

  2. Department of Psychiatry and Psychotherapy, Charité Campus Mitte, Charitéplatz 1, 10117, Berlin, Germany

    Astrid Knobel, Michael A. Rapp, Andreas Ströhle & Andreas Heinz

  3. Department of Psychiatry and Psychotherapy, University Hospital Tübingen, Tübingen, Germany

    Anil Batra

  4. Department of Psychiatry and Psychotherapy, University of Hamburg, Hamburg, Germany

    Klaus Wiedemann

  5. Department of Addiction Research, ZI Mannheim, University of Heidelberg, Mannheim, Germany

    Anke Zimmer

  6. Department of Psychiatry, University Hospital Leipzig, Leipzig, Germany

    Peter Schönknecht

  7. Section of Systems Neuroscience, Department of Psychiatry and Psychotherapy, Technische Universität Dresden, Dresden, Germany

    Michael N. Smolka

  8. National Institute of Mental Health, Bethesda, MD, USA

    Daniel R. Weinberger

  9. National Institute on Alcoholism and Alcohol Abuse, Bethesda, MD, USA

    David Goldman

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  1. Matthias Reimold
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  2. Astrid Knobel
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  3. Michael A. Rapp
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  10. Daniel R. Weinberger
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  11. David Goldman
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  12. Hans-Jürgen Machulla
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  13. Roland Bares
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  14. Andreas Heinz
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Corresponding author

Correspondence to Andreas Heinz.

Additional information

Reimold, Knobel, and Rapp contributed equally to this work.

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Reimold, M., Knobel, A., Rapp, M.A. et al. Central serotonin transporter levels are associated with stress hormone response and anxiety. Psychopharmacology 213, 563–572 (2011). https://doi.org/10.1007/s00213-010-1903-y

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  • DOI: https://doi.org/10.1007/s00213-010-1903-y

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