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Impact of COMT genotype on serotonin-1A receptor binding investigated with PET

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Abstract

Alterations of the inhibitory serotonin-1A receptor (5-HT1A) constitute a solid finding in neuropsychiatric research, particularly in the field of mood and anxiety disorders. Manifold factors influencing the density of this receptor have been identified, e.g., steroid hormones, sunlight exposure and genetic variants of serotonin-related genes. Given the close interactions between serotonergic and dopaminergic neurotransmission, we investigated whether a common single-nucleotide-polymorphism of the catechol-O-methyltransferase (COMT) gene (VAL158MET or rs4680) coding for a key enzyme of the dopamine network that is associated with the pathogenesis of mood disorders and antidepressant treatment response, directly affects 5-HT1A receptor binding potential. Fifty-two healthy individuals (38 female, mean age ± standard deviation = 40.48 ± 14.87) were measured via positron emission tomography using the radioligand [carbonyl-11C]WAY-100635. Genotyping for rs4680 was performed using DNA isolated from whole blood with the MassARRAY platform of the software SEQUENOM®. Whole brain voxel-wise ANOVA resulted in a main effect of genotype on 5-HT1A binding. Compared to A carriers (AA + AG) of rs4680, homozygote G subjects showed higher 5-HT1A binding potential in the posterior cingulate cortex (F (2,49) = 17.7, p = 0.05, FWE corrected), the orbitofrontal cortex, the anterior cingulate cortex, the insula, the amygdala and the hippocampus (voxel-level: p < 0.01 uncorrected, t > 2.4; cluster-level: p < 0.05 FWE corrected). In light of the frequently reported alterations of 5-HT1A binding in anxiety and mood disorders, this study proposes a potential implication of the COMT genotype, more specifically the VAL158MET polymorphism, via modulation of the serotonergic neurotransmission.

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Acknowledgments

This research was supported by funds of the Oesterreichische National Bank (Anniversary Fund, project number: 11468, 12809) to R. Lanzenberger and S. Kasper, respectively, and an intramural grant of the Department of Psychiatry and Psychotherapy (Forschungskostenstelle). A. Hahn was recipient of a DOC-fellowship of the Austrian Academy of Sciences (OeAW) at the Department of Psychiatry and Psychotherapy. We thank Stefanie Pichler for clinical support and Marie Spies for linguistic revision of the manuscript. We thank the PET team at the Division of Nuclear Medicine for technical support.

Conflict of interest

Without any relevance to this work, S. Kasper declares that he has received grant/research support from Eli Lilly, Lundbeck A/S, Bristol-Myers Squibb, Servier, Sepracor, GlaxoSmithKline, Organon, and has served as a consultant or on advisory boards for AstraZeneca, Austrian Sick Found, Bristol-Myers Squibb, GlaxoSmithKline, Eli Lily, Lundbeck A/S, Pfizer, Organon, Sepracor, Janssen, and Novartis, and has served on speakers’ bureaus for AstraZeneca, Eli Lilly, Lundbeck A/S, Servier, Sepracor and Janssen. R. Lanzenberger received travel grants and conference speaker honoraria from AstraZeneca and Lundbeck A/S. M. Mitterhauser and W. Wadsak received speaker honoraria from Bayer.

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Authors and Affiliations

  1. Functional, Molecular and Translational Neuroimaging Lab, Department of Psychiatry and Psychotherapy, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria

    Pia Baldinger, Andreas Hahn, Georg S. Kranz, Christoph Kraus, Siegfried Kasper & Rupert Lanzenberger

  2. Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria

    Markus Mitterhauser, Wolfgang Wadsak & Johanna Ungersböck

  3. Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University Munich, Munich, Germany

    Marion Friedl, Annette Hartmann, Ina Giegling & Dan Rujescu

  4. Department of Psychiatry, University of Halle, Halle, Germany

    Marion Friedl & Dan Rujescu

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  1. Pia Baldinger
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  2. Andreas Hahn
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  3. Markus Mitterhauser
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  4. Georg S. Kranz
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  5. Marion Friedl
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  7. Christoph Kraus
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  8. Johanna Ungersböck
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  9. Annette Hartmann
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  11. Dan Rujescu
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  12. Siegfried Kasper
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  13. Rupert Lanzenberger
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Corresponding author

Correspondence to Rupert Lanzenberger.

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Baldinger, P., Hahn, A., Mitterhauser, M. et al. Impact of COMT genotype on serotonin-1A receptor binding investigated with PET. Brain Struct Funct 219, 2017–2028 (2014). https://doi.org/10.1007/s00429-013-0621-8

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  • DOI: https://doi.org/10.1007/s00429-013-0621-8

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