Neuropsychological and conditioned blocking performance in patients with schizophrenia: assessment of the contribution of neuroleptic dose, serum levels and dopamine D2-receptor occupancy.
Patients with schizophrenia show impairments of attention and neuropsychological performance, but the extent to which this is attributable to antipsychotic medication remains largely unexplored. We describe here the putative influence of the dose of antipsychotic medication (chlorpromazine equivalents, CPZ), the antipsychotic serum concentration of dopamine (DA) D2-blocking activity and the approximated central dopamine D2-receptor occupancy (DA D2-occupancy), on conditioned blocking (CB) measures of attention and performance on a neuropsychological battery, in 108 patients with schizophrenia (compared with 62 healthy controls). Antipsychotic serum concentration and D2-occupancy were higher in patients with a paranoid versus non-paranoid diagnosis, and in female versus male patients (independent of symptom severity). Controlling for D2-occupancy removed the difference between high CB in paranoid and impaired low CB in non-paranoid patients. Similar partial correlations for antipsychotic drug dose and serum levels of DA D2-blocking activity with performance of the trail-making and picture completion tests (negative) and the block-design task (positive) showed the functional importance of DA-related activity. High estimates of central DA D2-occupancy were related to impaired verbal fluency but were associated with improved recall of stories, especially in paranoid patients. This, the first study of its kind, tentatively imputes a role for DA D2-related activity in left frontal (e.g. CB, verbal fluency) and temporal lobe functions (verbal recall) as well as in some non-verbal abilities mediated more in the right hemisphere in patients with schizophrenia.
Oades
R D
RD
University Clinic for Child and Adolescent Psychiatry and Psychotherapy, Essen, Germany. oades@uni-essen.de
Rao
M L
ML
Bender
S
S
Sartory
G
G
Müller
B W
BW
D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D001288:Attention / Q000187:drug effects*; D016022:Case-Control Studies; D002746:Chlorpromazine / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D003072:Cognition Disorders / Q000209:etiology* / Q000473:pathology; D003214:Conditioning, Classical; D004305:Dose-Response Relationship, Drug; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D006801:Humans; D008297:Male; D011939:Mental Recall; D010259:Paranoid Disorders / Q000503:physiopathology; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000502:physiology; D012559:Schizophrenia / Q000188:drug therapy* / Q000473:pathology; D012737:Sex Factors; D014145:Trail Making Test; D014705:Verbal Behavior / Q000187:drug effects* / Q000502:physiology
D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2; D002746:Chlorpromazine