PET study of D1 dopamine receptor binding in neuroleptic-naive patients with schizophrenia

Objective: Postmortem studies and a positron emission tomography (PET) study have suggested that there is a disturbance of central D1 dopamine receptor function in schizophrenia. The objective of the present PET study was to compare D1 receptor binding in first-admission, neuroleptic-naive patients with schizophrenia and in healthy subjects. Method: Ten healthy comparison subjects and 10 neuroleptic-naive patients with schizophrenia (diagnosed according to DSM-III-R) were examined twice by PET using 11C-labeled SCH 23390 ([11C]SCH 23390) with high and low specific radioactivity, respectively. The binding potential, receptor density (Bmax), and affinity (Kd) were determined for the caudate nucleus, the putamen, and several neocortical regions during both PET examinations. Scatchard plots from the two measurements were used to calculate regional D1 Bmax and Kd. The regional binding values were tested for hemispheric asymmetry and for correlation to clinical symptoms measured by the Brief Psychiatric Rating Scale (BPRS). Results: [11C]SCH 23390 binding to D1 receptors did not differ significantly between subjects with schizophrenia and healthy subjects in any of the brain regions or for any of the binding measures studied. Asymmetry of the regional binding values did not differ significantly between the two groups. Scores on the BPRS negative symptom subscale correlated significantly with the Bmax in the right frontal cortex. Conclusions: These results do not replicate previous postmortem and PET findings of altered central dopamine D1 receptor binding in schizophrenia. The finding of a positive correlation between frontal D1 binding and scores on the negative symptom subscale of the BPRS is contrary to a previously reported finding of a negative correlation. These discrepancies motivate further studies using D1 ligands with higher signals for cortical regions.