Neuropsychological and conditioned blocking performance in patients with schizophrenia: assessment of the contribution of neuroleptic dose, serum levels and dopamine D2-receptor occupancy
Introduction: Patients with schizophrenia are widely reported to show impairments of attention and neuropsychological performance, but the extent to which this is attributable to medication and dopamine (DA) function remains largely unexplored. Methods: We describe here the putative influence of 1) the dose of antipsychotic medication (chlorpromazine equivalents, CPZ), 2) the antipsychotic serum concentration (neuroleptic units in terms of butyrophenone displacement from animal neostriatum) and 3) the approximated DA D2-receptor occupancy in the brain (based on regression curves from 11 studies published for 5 neuroleptics) - - on conditioned blocking (CB) measures of attention and performance on a neuropsycholog-ical battery. We studied 108 patients with schizophrenia with 62 healthy controls. Results: 1) Antipsychotic serum concentration and D2-occupancy were higher in patients with a paranoid vs. non-paranoid diagnosis, and in female vs. male patients (independent of symptom severity). 2) Controlling for D2-occupancy removed the difference between high CB in paranoid and impaired low CB measures of selective attention in nonparanoid patients. 3) Similar partial correlations for antipsychotic drug dose and serum levels of DA D2-blocking activity with performance on the trail-making and picture completion tests (negative) and the block-design test (positive) showed the functional importance of DA-related activity. 4) High estimates of D2-occupancy were related to impaired verbal fluency - but - were associated with improved recall of stories, especially in paranoid patients. 5) Non-dopaminergic aspects of medication (i.e. CPZ-dependent but not D2-occupancy-associated) impaired verbal recall in males (left-hemisphere function) and non-verbal performance in females (reflecting right hemisphere function). Conclusions: This first study of its kind tentatively imputes a role for DA D2-related activity in left frontal (e.g. CB and verbal fluency) and temporal lobe functions (verbal recall), as well as in some non-verbal abilities mediated more in the right hemisphere of patients with schizophrenia
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