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Serotonergic modulation of resting state default mode network connectivity in healthy women

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Abstract

The default mode network (DMN) plays a central role in intrinsic thought processes. Altered DMN connectivity has been linked to diminished cerebral serotonin synthesis. Diminished brain serotonin synthesis is further associated with a lack of impulse control and various psychiatric disorders. Here, we investigated the serotonergic modulation of intrinsic functional connectivity (FC) within the DMN in healthy adult females, controlling for the menstrual cycle phase. Eighteen healthy women in the follicular phase (aged 20–31 years) participated in a double-blind controlled cross-over study of serotonin depletion. Acute tryptophan depletion (ATD) and a balanced amino acid load (BAL), used as the control condition, were applied on two separate days of assessment. Neural resting state data using functional magnetic resonance imaging (fMRI) and individual trait impulsivity scores were obtained. ATD compared with BAL significantly reduced FC with the DMN in the precuneus (associated with self-referential thinking) and enhanced FC with the DMN in the frontal cortex (associated with cognitive reasoning). Connectivity differences with the DMN between BAL and ATD in the precentral gyrus were significantly correlated with the magnitude of serotonin depletion. Right medial frontal gyrus and left superior frontal gyrus connectivity differences with the DMN were inversely correlated with trait impulsivity. These findings partially deviate from previous findings obtained in males and underline the importance of gender-specific studies and controlling for menstrual cycle to further elucidate the mechanism of ATD-induced changes within intrinsic thought processes.

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Acknowledgments

We would like to thank the participants for their support. We would also like to thank Theodor Schmitt for his support in conducting the measurements and the Brain Imaging Facility of the Interdisciplinary Centre for Clinical Research within the Faculty of Medicine at the RWTH Aachen University, Germany for further support in fMRI measurement and analysis.

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Authors and Affiliations

  1. RWTH Aachen University, Clinic for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Aachen, Germany

    K. Helmbold, B. Dahmen, C. S. Biskup, S. Bubenzer-Busch, T. J. Gaber, K. Konrad, B. Herpertz-Dahlmann & F. D. Zepf

  2. Jülich Aachen Research Alliance, JARA Translational Brain Medicine, Aachen, Germany

    K. Helmbold, M. Zvyagintsev, C. S. Biskup, S. Bubenzer-Busch, T. J. Gaber, M. Klasen, K. Konrad, U. Habel, B. Herpertz-Dahlmann & F. D. Zepf

  3. Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany

    M. Zvyagintsev, M. Klasen & U. Habel

  4. Department of Pharmacy, RWTH Aachen University, Aachen, Germany

    A. Eisert

  5. Institute for Neuroscience and Medicine, Jülich Research Centre, Jülich, Germany

    K. Konrad & F. D. Zepf

  6. Department of Child and Adolescent Psychiatry, School of Psychiatry & Clinical Neurosciences and School of Paediatrics & Child Health, The University of Western Australia, Perth, WA, Australia

    F. D. Zepf

  7. Specialised Child and Adolescent Mental Health Services (CAMHS), Department of Health in Western Australia, Perth, WA, Australia

    F. D. Zepf

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  1. K. Helmbold
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  2. M. Zvyagintsev
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  3. B. Dahmen
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  4. C. S. Biskup
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  5. S. Bubenzer-Busch
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  6. T. J. Gaber
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  8. A. Eisert
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  9. K. Konrad
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  10. U. Habel
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  11. B. Herpertz-Dahlmann
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  12. F. D. Zepf
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Corresponding author

Correspondence to F. D. Zepf.

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Funding for this study was provided by the START research funding scheme of the RWTH Aachen University Hospital, Germany. The funder had no role in the study design, in the collection, analysis and interpretation of data, in writing the report, or in the decision to submit the paper for publication.

KH, MZ, TJG, MC, BD, SB, MK, AE, KK and UH do not have any real or potential conflicts of interest and have not received any travel support or honoraria from a commercial business. BHD serves as an advisory board member for Eli Lilly and Company and received research support from Vifor Pharma Ltd. In the past six years, FDZ was the recipient of an unrestricted award donated by the American Psychiatric Association (APA), the American Psychiatric Institute for Research and Education (APIRE), and AstraZeneca (the Young Minds in Psychiatry Award). He has also received research support from the German Federal Ministry for Economics and Technology, the European Union (EU), the German Society for Social Pediatrics and Adolescent Medicine, the Paul and Ursula Klein Foundation, the Dr. August Scheidel Foundation and the IZKF of RWTH Aachen University and a travel stipend donated by the GlaxoSmithKline Foundation. He is the recipient of an unrestricted educational grant, travel support and speaker honoraria from Shire Pharmaceuticals, Germany, as well as of editorial fees from Co-Action Publishing (Sweden). In addition, he has received support from the Raine Foundation for Medical Research (Raine Visiting Professorship). The other authors have nothing to disclose or report.

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Helmbold, K., Zvyagintsev, M., Dahmen, B. et al. Serotonergic modulation of resting state default mode network connectivity in healthy women. Amino Acids 48, 1109–1120 (2016). https://doi.org/10.1007/s00726-015-2137-4

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