Dopamine receptor density and white mater integrity: 18F-fallypride positron emission tomography and diffusion tensor imaging study in healthy and schizophrenia subjects

  • Serge A. MitelmanEmail author
  • Monte S. Buchsbaum
  • Bradley T. Christian
  • Brian M. Merrill
  • Bradley R. Buchsbaum
  • Jogeshwar Mukherjee
  • Douglas S. Lehrer


Dopaminergic dysfunction and changes in white matter integrity are among the most replicated findings in schizophrenia. A modulating role of dopamine in myelin formation has been proposed in animal models and healthy human brain, but has not yet been systematically explored in schizophrenia. We used diffusion tensor imaging and 18F-fallypride positron emission tomography in 19 healthy and 25 schizophrenia subjects to assess the relationship between gray matter dopamine D2/D3 receptor density and white matter fractional anisotropy in each diagnostic group. AFNI regions of interest were acquired for 42 cortical Brodmann areas and subcortical gray matter structures as well as stereotaxically placed in representative white matter areas implicated in schizophrenia neuroimaging literature. Welch’s t-test with permutation-based p value adjustment was used to compare means of z-transformed correlations between fractional anisotropy and 18F-fallypride binding potentials in hypothesis-driven regions of interest in the diagnostic groups. Healthy subjects displayed an extensive pattern of predominantly negative correlations between 18F-fallypride binding across a range of cortical and subcortical gray matter regions and fractional anisotropy in rostral white matter regions (internal capsule, frontal lobe, anterior corpus callosum). These patterns were disrupted in subjects with schizophrenia, who displayed significantly weaker overall correlations as well as comparatively scant numbers of significant correlations with the internal capsule and frontal (but not temporal) white matter, especially for dopamine receptor density in thalamic nuclei. Dopamine D2/D3 receptor density and white matter integrity appear to be interrelated, and their decreases in schizophrenia may stem from hyperdopaminergia with dysregulation of dopaminergic impact on axonal myelination.


White matter Myelin Dopamine Thalamus Hyperdopaminergia Schizophrenia 



This work was supported by the Kettering Health Network Foundation. The support of the United States Air Force, Air Force Research Laboratory (AFRL/HEOP), Air Force Materiel Command, under cooperative agreement F33615-98-2-6002, for use of imaging resources, is gratefully acknowledged. The project was approved by the institutional review boards of the Kettering Health Network, Wright State University and Icahn School of Medicine at Mount Sinai.

Compliance with ethical standards

Conflict of interest

Informed consent was obtained from all individual participants included in the study.

The authors declare that they have no conflict of interests.

The project was approved by the institutional review boards of the Kettering Health Network, Wright State University and Icahn School of Medicine at Mount Sinai.

Supplementary material

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of PsychiatryIcahn School of Medicine at Mount SinaiNew YorkUSA
  2. 2.Department of Psychiatry, Division of Child and Adolescent PsychiatryElmhurst Hospital CenterElmhurstUSA
  3. 3.Departments of Psychiatry and RadiologyUniversity of CaliforniaSan DiegoUSA
  4. 4.Department of Psychiatry and Human Behavior, Irvine School of MedicineUniversity of CaliforniaOrangeUSA
  5. 5.Waisman Laboratory for Brain Imaging and BehaviorUniversity of Wisconsin-MadisonMadisonUSA
  6. 6.Department of Psychiatry, Boonshoft School of MedicineWright State UniversityDaytonUSA
  7. 7.The Rotman Research Institute, Baycrest Centre for Geriatric Care and Department of PsychiatryUniversity of TorontoTorontoCanada
  8. 8.Department of Radiological Sciences, Preclinical Imaging, Irvine School of MedicineUniversity of CaliforniaIrvineUSA

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