D2 receptor blockade by risperidone correlates with attention deficits in late-life schizophrenia.
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.
Uchida
Hiroyuki
H
PET Centre, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
Rajji
Tarek K
TK
Mulsant
Benoit H
BH
Kapur
Shitij
S
Pollock
Bruce G
BG
Graff-Guerrero
Ariel
A
Menon
Mahesh
M
Mamo
David C
DC
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
D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D018967:Risperidone