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. 2009 Jun 15;65(12):1024-31.
doi: 10.1016/j.biopsych.2008.12.029. Epub 2009 Feb 28.

Dopamine D2 receptor levels in striatum, thalamus, substantia nigra, limbic regions, and cortex in schizophrenic subjects

Robert M Kessler  1 , Neil D Woodward, Patrizia Riccardi, Rui Li, M Sib Ansari, Sharlett Anderson, Benoit Dawant, David Zald, Herbert Y Meltzer
Affiliations

Dopamine D2 receptor levels in striatum, thalamus, substantia nigra, limbic regions, and cortex in schizophrenic subjects

Robert M Kessler et al. Biol Psychiatry. .

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: [(18)F]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 D(2) receptor (DA D(2)r) 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 D(2)r 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 D(2)r 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 D(2)r-mediated neurotransmission in the substantia nigra consistent with nigral dysfunction in schizophrenia and suggest that both temporal cortical and ventral striatal DA D(2)r mediate positive symptoms.

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Conflict of interest statement

Dr. Kessler has investigator initiated research support from Janssen, consults with and is a shareholder in PharmorRx. Dr. Herbert Meltzer has been a consultant to and received grants from Abbot, ACADIA, ARYx, BioLine Rx, Bristol Myers Squibb, Cephalon, Eli Lilly, Janssen, Litmus Molecular Design, Memory, Minster, and Pfizer. Dr Meltzer has been a consultant to Astellas, Glaxo Smith Kline, Lundbeck, Merck, Otsuka, Roche, and Solvay, and has received grants from Dainippon Sumitomo, Sepreacor, and SK Pharma. Drs. Woodward, Riccardi, Dawant, and Zald, Mr. Ansari and Li, and Ms. Anderson have no biomedical financial interests or potential conflicts of interest.

Figures

Figure 1
Figure 1
Sagittal (A,B), axial (C), and coronal (D) images through significant clusters of correlations of total SAPS scores with regional DA D2r levels. Two significant clusters are seen involving the posterior portions of the inferior, middle and superior temporal gyri with extension superiorly into the supramarginal gyrus of the parietal lobe in both cerebral hemispheres. The cluster on the right (146 voxels, mean r =0.85) was similar in size to the cluster on the left (131 voxels, mean r=0.86)
Figure 2
Figure 2
Two significant clusters of correlations of the SAPS global score for delusions with DA D2r levels are seen in the right and left anterolateral temporal cortex extending into the temporal tips. The cluster on the left (80 voxels on the left, mean r=0.86) is larger than the cluster on the right (50 voxels on the right, mean r=0.84).
Figure 3
Figure 3
Sagittal left (A) and right (B), axial (C), and coronal (D) images through significant clusters of correlations of SAPS global scores for bizarre behavior with regional DA D2r levels. Two significant clusters of highly positive correlations (184 voxels on the right, mean r=0.85; 179 voxels on the left, mean r=0.84) involve the mid to posterior lateral aspects of the temporal lobes with extension into the inferior parietal lobule
Figure 4
Figure 4
A significant cluster of correlations (31 voxels, mean r = 0.84) of the SAPS global score for hallucinations with DA D2r levels is seen in the left ventral striatum. No other significant clusters of correlations were seen.
See this image and copyright information in PMC

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