D2/D3 Dopamine Receptor Binding with [F-18]fallypride correlates of executive function in medication-naïve patients with schizophrenia

Nora S Vyas1,2,3, Douglas S Lehrer4, Brian Merrill4, Alex DeCastro5, Nicholas A Doninger6, Bradley T Christian7, Monte S Buchsbaum5; 1Kingston University London, 2National Institutes of Health, 3Imperial College Healthcare NHS Trust, 4Wright State University, 5University of California San Diego, 6Wright State University SOM, 7University of Wisconsin-Madison

Purpose: To investigate the association between D2/D3 receptor binding and cognitive performance in unmedicated patients with schizophrenia. Materials and methods: Resting-state 18F-fallypride positron emission tomography was performed on 25 unmedicated patients with schizophrenia (mean age, 31.4 +/- 12.32) and 19 age and sex-matched healthy volunteers (mean age, 29.2 +/- 9.25). Striatal and extra-striatal dopamine D2/D3 receptor levels were quantified as binding potential. MRI images in standard Talairach position and segmented into gray and white matter were co-registered to the fallypride images and the AFNI stereotaxic atlas applied. Two neuropsychological tasks subserved by the frontal and temporal lobes were chosen, the Wisconsin Card Sorting Task (WCST), and the California Verbal Learning Test. Results: Patients showed a negative correlation between WCST categories achieved and the medial dorsal nucleus of the thalamus, previously found to have lower binding potential in patients than healthy volunteers. Correlations between neuropsychological performance and Fallypride binding potential tended to be positive in healthy volunteers and negative in never-medicated patients with schizophrenia. Since low binding potential may be associated with more dopamine in the synapse, we expected positive correlations. Conclusions: Our results are consistent with the both positive and negative correlations observed in previous studies of neuropsychological performance and dopamine binding correlations. The findings suggest an adaptive advantage of enhanced dopamine levels in the never-medicated group and that a differential pattern of regional dopamine function may be present in patients with schizophrenia.

Topic Area: Neuroimaging

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