Neuropsychological and conditioned blocking performance in patients with schizophrenia: assessment of the contribution of neuroleptic dose, serum levels and dopamine D-2-receptor occupancy

Patients with schizophrenia show impairments of attention and neuropsycholo gical performance, but the extent to which this is attributable to antipsyc hotic medication remains largely unexplored. We describe here the putative influence of the dose of antipsychotic medication (chlorpromazine equivalen ts, CPZ), the antipsychotic serum concentration of dopamine (DA) D-2-blocki ng activity and the approximated central dopamine D-2-receptor occupancy (D A D-2-occupancy), on conditioned blocking (CB) measures of attention and pe rformance on a neuropsychological battery, in 108 patients with schizophren ia (compared with 62 healthy controls). Antipsychotic serum concentration a nd D-2-occupancy were higher in patients with a paranoid versus non-paranoi d diagnosis, and in female versus male patients (independent of symptom sev erity). Controlling for D-2-occupancy removed the difference between high C B in paranoid and impaired low CB in non-paranoid patients. Similar partial correlations for antipsychotic drug dose and serum levels of DA D-2-blocki ng activity with performance of the trail-making and picture completion tes ts (negative) and the block-design task (positive) showed the functional im portance of DA-related activity. High estimates of central DA D-2-occupancy were related to impaired verbal fluency but were associated with improved recall of stories, especially in paranoid patients. This, the first study o f its kind, tentatively imputes a role for DA D-2-related activity in left frontal (e.g. CB, verbal fluency) and temporal lobe functions (verbal recal l) as well as in some non-verbal abilities mediated more in the right hemis phere in patients with schizophrenia. (C) 2000 Lippincott Williams & Wilkin s.