Positive association between cerebral grey matter metabolism and dopamine D₂/D₃ receptor availability in healthy and schizophrenia subjects: An ¹⁸F-fluorodeoxyglucose and ¹⁸F-fallypride positron emission tomography study

Abstract

Objectives: Overlapping decreases in extrastriatal dopamine D₂/D₃-receptor availability and glucose metabolism have been reported in subjects with schizophrenia. It remains unknown whether these findings are physiologically related or coincidental.

Methods: To ascertain this, we used two consecutive ¹⁸F-fluorodeoxyglucose and ¹⁸F-fallypride positron emission tomography scans in 19 healthy and 25 unmedicated schizophrenia subjects. Matrices of correlations between ¹⁸F-fluorodeoxyglucose uptake and ¹⁸F-fallypride binding in voxels at the same xyz location and AFNI-generated regions of interest were evaluated in both diagnostic groups.

Results: ¹⁸F-fluorodeoxyglucose uptake and ¹⁸F-fallypride binding potential were predominantly positively correlated across the striatal and extrastriatal grey matter in both healthy and schizophrenia subjects. In comparison to healthy subjects, significantly weaker correlations in subjects with schizophrenia were confirmed in the right cingulate gyrus and thalamus, including the mediodorsal, lateral dorsal, anterior, and midline nuclei. Schizophrenia subjects showed decreased D₂/D₃-receptor availability in the hypothalamus, mamillary bodies, thalamus and several thalamic nuclei, and increased glucose uptake in three lobules of the cerebellar vermis.

Conclusions: Dopaminergic system may be involved in modulation of grey matter metabolism and neurometabolic coupling in both healthy human brain and psychopathology. Hyperdopaminergic state in untreated schizophrenia may at least partly account for the corresponding decreases in grey matter metabolism.

Keywords:

• Dopamine receptor availability
• hyperdopaminergia
• neurometabolic coupling
• thalamus
• cerebellum

Acknowledgements

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Statement of interest

None to declare.

Additional information

Funding

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.