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Reduced ventral striatal/ventral pallidal serotonin1B receptor binding potential in major depressive disorder

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Abstract

Rationale

Although serotonin (5-HT) dysregulation is implicated in the pathophysiology of major depressive disorder (MDD), the role of specific receptor subtypes remains to be elucidated. Emerging preclinical research suggests an important role for the 5-HT1B receptor in behavioral regulation and depressive phenotypes. In particular, 5-HT1B heteroreceptors located within the striatum have been shown to play an essential role in antidepressant action.

Objectives

The objective of this study was to determine 5-HT1B receptor binding potential (BP ND) in the region of the ventral striatum/ventral pallidum (VS/VP) in individuals with MDD and healthy control participants.

Methods

Ten participants with MDD (30.8 ± 9.5 years, five men/five women) in a current major depressive episode (MDE) and ten healthy control participants (30.7 ± 10.5 years, five men/five women) underwent positron emission tomography (PET) scanning with the selective 5-HT1B receptor radioligand [11C]P943.

Results

Within the VS/VP region of interest, [11C]P943 BP ND was significantly reduced in the MDD group compared with the healthy control group (1.37 ± 0.13 and 1.68 ± 0.16, respectively; 18.7% between-group difference; p < 0.001).

Conclusions

Consistent with preclinical and postmortem data, our findings suggest abnormally reduced function of VS/VP 5-HT1B receptors in humans with MDD. Abnormal 5-HT1B heteroreceptor function may contribute to dysfunctional reward signaling within the striatum, including the nucleus accumbens, via interaction with dopamine, γ-amino-butyric acid, or glutamate systems. Our findings suggest reduced 5-HT1B receptor signaling in the VS/VP in MDD and contribute to the therapeutic rationale for testing 5-HT1B agonists as a novel class of antidepressants.

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Acknowledgments

This study was supported by the National Institute of Mental Health grant R21 MH081103 (ARRA) and grant R21 MH085627, and the VA National Center for Posttraumatic Stress Disorder at the West Haven VA Connecticut Clinical Neurosciences Division.

The authors acknowledge the excellent work of the staff of the Yale PET Center and the nursing support from Sue Kasserman, R.N. for help in recruitment and patient care and Brenda Breault, R.N., B.S.N. for her contributions with patient care during the PET scans. In addition, we acknowledge the Yale-Pfizer Bioimaging Alliance for support in the development of [11C]P943.

Conflict of interest

Dr. Neumaier reports lecture fees from Eli Lilly and Wyeth, and Dr. Neumeister grant support from Pfizer Inc., Eli Lilly, UCB Pharma Inc., and Ortho-McNeil Janssen Scientific Affairs, LLC.; Dr. Neumeister has grant support from Pfizer Inc., Eli Lilly, UCB Pharma Inc., and Ortho-McNeil Janssen Scientific Affairs, LLC. No other potential conflict of interest relevant to this article was reported. The contents of the manuscript are solely the responsibility of the authors and do not necessarily represent the official views of any of the funding agencies.

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Authors and Affiliations

  1. Mood and Anxiety Disorders Program, Department of Psychiatry, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1230, New York, NY, 10029, USA

    James W. Murrough & Alexander Neumeister

  2. Molecular Imaging Program, Clinical Neurosciences Division, VA National Center for PTSD, VA Connecticut Healthcare System, West Haven, CT, USA

    Shannan Henry, Jian Hu & Alexander Neumeister

  3. Positron Emission Tomography Center, Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, USA

    Jean-Dominique Gallezot & Beata Planeta-Wilson

  4. Department of Psychiatry, University of Washington, Seattle, WA, USA

    John F. Neumaier

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  1. James W. Murrough
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  2. Shannan Henry
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  4. Jean-Dominique Gallezot
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Correspondence to Alexander Neumeister.

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Murrough, J.W., Henry, S., Hu, J. et al. Reduced ventral striatal/ventral pallidal serotonin1B receptor binding potential in major depressive disorder. Psychopharmacology 213, 547–553 (2011). https://doi.org/10.1007/s00213-010-1881-0

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  • DOI: https://doi.org/10.1007/s00213-010-1881-0

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