Relationship of frontal D(2/3) binding potentials to cognition: a study of antipsychotic-naive schizophrenia patients.

Studies of in vivo dopamine receptors in schizophrenia have mostly focused on D(2) receptors in striatal areas or on D(1) receptors in cortex. No previous study has examined the correlation between cortical dopamine D(2/3) receptor binding potentials and cognition in schizophrenia patients. The objective was to examine this relation in the frontal cortex in first-episode, drug-naive schizophrenia patients. Based on preclinical and pharmacological evidence, we specifically expected to find a relation between D(2/3) receptor binding potentials and set shifting. This was a cross-sectional, case-control study using single-photon emission computerized tomography with the D(2/3)-receptor ligand [(123)I]epidepride, co-registered with structural magnetic resonance imaging and correlated to cognitive measures. Participants were 24 antipsychotic-naive, first-episode schizophrenia patients and 20 healthy controls matched for gender and age. For patients, a significant linear correlation between D(2/3) BP(ND) and set shifting was found, while significant quadratic associations were observed for verbal fluency, planning and attention. For controls, the only significant association with D(2/3) BP(ND) was a quadratic partial correlation for set shifting. The main findings indicated a relation between D(2/3) receptor binding in the frontal cortex and set shifting, planning and attention, but also support a differential involvement of cortical dopamine D(2/3) receptor binding in at least some cognitive functions, perhaps particularly attention, in schizophrenia patients compared to healthy people. The results suggest that cortical D(2/3) receptor function may be more involved in some cognitive functions (i.e. attention, fluency and planning) in patients with schizophrenia than in healthy people, suggesting that information processing in schizophrenia may be characterized by lower signal:noise ratios.