title: D2 receptor blockade by risperidone correlates with attention deficits in late-life schizophrenia.
abstract: The negative impact of antipsychotic drugs on attention is expected to be greater in late-life schizophrenia because of the age-related changes in the dopamine receptor reserve. The objective of this study was to examine the relationship between dopamine D2 receptor blockade by risperidone and the cognitive function in late-life schizophrenia. Subjects with schizophrenia or schizoaffective disorder aged 50 or older who were receiving risperidone completed a [C]raclopride positron emission tomography scan to measure D2-binding potential in the striatum. The D2 receptor blockade by risperidone was calculated using age-corrected measures from healthy individuals and region of interest analysis of dynamic positron emission tomography data coregistered to the subjects' magnetic resonance imaging scans. Cognitive function was assessed using a battery of neuropsychological tests that included the Dementia Rating Scale-2 (DRS). Eleven subjects (mean +/- SD age, 64 +/- 8 years) participated in this study. The mean +/- SD D2 receptor blockade was 69% +/- 14% (range, 34%-80%). The age-corrected score on the attention subscale in the DRS was negatively correlated with the D2 receptor blockade. The DRS attention subscale score was lower in the subjects who experienced 74.9% or higher D2 blockade (median value, corresponding to a daily risperidone dose of >3.0 mg) than in those who did not. Although a causal attribution cannot be made in light of the cross-sectional nature of this study, the results suggest the critical importance of identifying the lowest effective dose of antipsychotic drugs in older patients with schizophrenia.
authors.affiliation: PET Centre, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Uchida
authors.forename: Tarek K
authors.initials: TK
authors.lastname: Rajji
authors.forename: Benoit H
authors.initials: BH
authors.lastname: Mulsant
authors.forename: Shitij
authors.initials: S
authors.lastname: Kapur
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Pollock
authors.forename: Ariel
authors.initials: A
authors.lastname: Graff-Guerrero
authors.forename: Mahesh
authors.initials: M
authors.lastname: Menon
authors.forename: David C
authors.initials: DC
authors.lastname: Mamo
mesh_terms: D017668:Age of Onset; D000368:Aged; D001289:Attention Deficit Disorder with Hyperactivity / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000453:epidemiology; D003430:Cross-Sectional Studies; D018492:Dopamine Antagonists / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D065127:Dopamine D2 Receptor Antagonists; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D018967:Risperidone / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D012559:Schizophrenia / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000453:epidemiology
chemical_list: D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D018967:Risperidone