Striatal and extrastriatal dopamine D2/D3 receptors in schizophrenia evaluated with [18F]fallypride positron emission tomography

Lawrence S. Kegeles, Mark Slifstein, Xiaoyan Xu, Nina Urban, Judy L. Thompson, Tiffany Moadel, Jill M. Harkavy-Friedman, Roberto Gil, Marc Laruelle, Anissa Abi-Dargham

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

Background: Alterations in dopamine D2/D3 receptor binding have been reported in schizophrenia, and a meta-analysis of imaging studies has shown a modest elevation in striatum. Newer radioligands now allow the assessment of these receptors in extrastriatal regions. We used positron emission tomography with [18F]fallypride to evaluate D 2/D3 receptors in both striatal and extrastriatal regions in schizophrenia. Methods: Twenty-one patients with schizophrenia and 22 matched healthy control subjects were scanned with an ECAT EXACT HR+ camera. Two-tissue compartment modeling and the reference tissue method gave binding potentials relative to nondisplaceable uptake, total plasma concentration, and free plasma concentration. These were compared between groups in five striatal and eight extrastriatal regions. Several regional volumes were lower in the patient group, and positron emission tomography data were corrected for partial volume effects. Results: Binding potential values differed in three regions between groups. Values for binding potential relative to nondisplaceable uptake from two-tissue compartment modeling in patients and control subjects, respectively, were 28.7 ± 6.8 and 25.3 ± 4.3 in postcommissural caudate, 2.9 ± .7 and 2.6 ± .4 in thalamus, and 1.8 ± .5 and 2.1 ± .7 in uncus. Loss of D2/D3 receptors with age was found in striatal and extrastriatal regions and was greater in neocortex. Conclusions: Our study found selective alterations in D2/D 3 receptors in striatal and extrastriatal regions, consistent with some but not all previously published reports. As previously shown for the striatum, a more sensitive imaging approach for studying the role of dopamine in the pathophysiology of schizophrenia might be assessment of neurotransmitter levels rather than D2/D3 receptor levels in extrastriatal regions.

Original languageEnglish (US)
Pages (from-to)634-641
Number of pages8
JournalBiological Psychiatry
Volume68
Issue number7
DOIs
StatePublished - Oct 1 2010

All Science Journal Classification (ASJC) codes

  • Biological Psychiatry

Keywords

  • Age-related D/D receptor loss
  • dopamine D /D receptor
  • extrastriatal regions
  • fallypride
  • partial volume correction
  • positron emission tomography
  • schizophrenia

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    Kegeles, L. S., Slifstein, M., Xu, X., Urban, N., Thompson, J. L., Moadel, T., Harkavy-Friedman, J. M., Gil, R., Laruelle, M., & Abi-Dargham, A. (2010). Striatal and extrastriatal dopamine D2/D3 receptors in schizophrenia evaluated with [18F]fallypride positron emission tomography. Biological Psychiatry, 68(7), 634-641. https://doi.org/10.1016/j.biopsych.2010.05.027