PET study of D(1) dopamine receptor binding in neuroleptic-naive patients with schizophrenia

Abstract

Objective: Postmortem studies and a positron emission tomography (PET) study have suggested that there is a disturbance of central D(1) dopamine receptor function in schizophrenia. The objective of the present PET study was to compare D(1) 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 (11)C-labeled SCH 23390 ([(11)C]SCH 23390) with high and low specific radioactivity, respectively. The binding potential, receptor density (B(max)), and affinity (K(d)) 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 D(1) B(max) and K(d). The regional binding values were tested for hemispheric asymmetry and for correlation to clinical symptoms measured by the Brief Psychiatric Rating Scale (BPRS).

Results: [(11)C]SCH 23390 binding to D(1) 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 B(max) in the right frontal cortex.

Conclusions: These results do not replicate previous postmortem and PET findings of altered central dopamine D(1) receptor binding in schizophrenia. The finding of a positive correlation between frontal D(1) 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 D(1) ligands with higher signals for cortical regions.