Dopamine D2 Receptor Levels in Striatum, Thalamus, Substantia Nigra, Limbic Regions, and Cortex in Schizophrenic Subjects

Robert M. Kessler*, Neil D. Woodward, Patrizia Riccardi, Rui Li, M. Sib Ansari, Sharlett Anderson, Benoit Dawant, David Zald, Herbert Y. Meltzer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

100 Scopus citations

Abstract

Background: Studies in schizophrenic patients have reported dopaminergic abnormalities in striatum, substantia nigra, thalamus, anterior cingulate, hippocampus, and cortex that have been related to positive symptoms and cognitive impairments. Methods: [18F]fallypride positron emission tomography studies were performed in off-medication or never-medicated schizophrenic subjects (n = 11, 6 men, 5 women; mean age of 30.5 ± 8.0 [SD] years; 4 drug-naive) and age-matched healthy subjects (n = 11, 5 men, 6 women, mean age of 31.6 ± 9.2 [SD]) to examine dopamine D2 receptor (DA D2r) levels in the caudate, putamen, ventral striatum, medial thalamus, posterior thalamus, substantia nigra, amygdala, temporal cortex, anterior cingulate, and hippocampus. Results: In schizophrenic subjects, increased DA D2r levels were seen in the substantia nigra bilaterally; decreased levels were seen in the left medial thalamus. Correlations of symptoms with ROI data demonstrated a significant correlation of disorganized thinking/nonparanoid delusions with the right temporal cortex ROI (r = .94, p = .0001), which remained significant after correction for multiple comparisons (p < .03). Correlations of symptoms with parametric images of DA D2r levels revealed no significant clusters of correlations with negative symptoms but significant clusters of positive correlations of total positive symptoms, delusions and bizarre behavior with the lateral and anterior temporal cortex, and hallucinations with the left ventral striatum. Conclusions: The results of this study demonstrate abnormal DA D2r-mediated neurotransmission in the substantia nigra consistent with nigral dysfunction in schizophrenia and suggest that both temporal cortical and ventral striatal DA D2r mediate positive symptoms.

Original languageEnglish (US)
Pages (from-to)1024-1031
Number of pages8
JournalBiological psychiatry
Volume65
Issue number12
DOIs
StatePublished - Jun 15 2009

Keywords

  • Delusions
  • dopamine D receptors
  • fallypride
  • hallucinations
  • schizophrenia
  • substantia nigra
  • thalamus

ASJC Scopus subject areas

  • Biological Psychiatry

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