Brain Structure and Function

, Volume 223, Issue 6, pp 2609–2625 | Cite as

In vivo relationship between serotonin 1A receptor binding and gray matter volume in the healthy brain and in major depressive disorder

  • Francesca ZanderigoEmail author
  • Spiro Pantazatos
  • Harry Rubin-Falcone
  • R. Todd Ogden
  • Binod Thapa Chhetry
  • Gregory Sullivan
  • Maria Oquendo
  • Jeffrey M. Miller
  • J. John Mann
Original Article


Serotonin 1A (5-HT1A) receptors mediate serotonin trophic role in brain neurogenesis. Gray matter volume (GMV) loss and 5-HT1A receptor binding alterations have been identified in major depressive disorder (MDD). Here we investigated the relationship between 5-HT1A receptor binding and GMV in 40 healthy controls (HCs) and, for the first time, 47 antidepressant-free MDD patients using Voxel-Based Morphometry and [11C]WAY100635 Positron Emission Tomography. Values of GMV and 5-HT1A binding (expressed as BPF, one of the types of binding potentials that refer to displaceable or specific binding that can be quantified in vivo with PET) were obtained in 13 regions of interest, including raphe, and at the voxel level. We used regression analysis within each group to predict GMV from BPF, while covarying for age, sex, total gray matter volume and medication status. In the HCs group, we found overall a positive correlation between terminal field 5-HT1A receptor binding and GMV, which reached statistical significance in regions such as hippocampus, insula, orbital prefrontal cortex, and parietal lobe. We observed a trend towards inverse correlation between raphe 5-HT1A autoreceptor binding and anterior cingulate GMV in both groups, and a statistically significant positive correlation between raphe 5-HT1A binding and temporal GMV in MDD. Analysis of covariance at the voxel-level revealed a trend towards interaction between diagnosis and raphe 5-HT1A binding in predicting GMV in cerebellum and supramarginal gyrus (higher correlation in HCs compared with MDD). Our results replicated previous findings in the normative brain, but did not extend them to the brain in MDD, and indicated a trend towards dissociation between MDD and HCs in the relationship of raphe 5-HT1A binding with postsynaptic GMV. These results suggest that 5-HT1A receptors contribute to altered neuroplasticity in MDD, possibly via effects predating depression onset.


Positron emission tomography Magnetic resonance imaging Serotonin 1A receptor Gray matter volume Major depressive disorder 


Compliance with ethical standards

Conflict of interest

Drs. Zanderigo and Ogden, Mr. Rubin-Falcone and Mr. Binod Thapa Chhetry have no conflicts of interest to declare. Dr. Pantazatos’s contribution to this work was supported by NIMH K01MH108721. Drs. Mann and Oquendo receive royalties for commercial use of the Columbia-Suicide Severity Rating Scales from the Research Foundation for Mental Hygeine and Dr. Oquendo receives an honorarium as President of the American Psychiatric Association. Her family owns stock in Bristol Myers Squibb. Dr. Miller’s family previously owned stock in Johnson & Johnson, unrelated to the current manuscript. Dr. Sullivan is currently employed by Tonix Pharmaceuticals, Inc. and holds stock in the same, unrelated to the current manuscript.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Francesca Zanderigo
    • 1
    • 2
    Email author
  • Spiro Pantazatos
    • 1
    • 2
  • Harry Rubin-Falcone
    • 1
  • R. Todd Ogden
    • 1
    • 2
    • 3
  • Binod Thapa Chhetry
    • 1
  • Gregory Sullivan
    • 1
  • Maria Oquendo
    • 1
    • 2
  • Jeffrey M. Miller
    • 1
    • 2
  • J. John Mann
    • 1
    • 2
    • 4
  1. 1.Molecular Imaging and Neuropathology DivisionNew York State Psychiatric InstituteNew YorkUSA
  2. 2.Department of PsychiatryColumbia UniversityNew YorkUSA
  3. 3.Department of BiostatisticsColumbia University, Mailman School of Public HealthNew YorkUSA
  4. 4.Department of RadiologyColumbia UniversityNew YorkUSA

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