Tarek K Rajji1, Benoit H Mulsant2, Shinichiro Nakajima3, Fernando Caravaggio4, Takefumi Suzuki5, Hiroyuki Uchida6, Philip Gerretsen7, Wanna Mar8, Bruce G Pollock2, David C Mamo9, Ariel Graff-Guerrero7. 1. Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. Electronic address: Tarek.Rajji@camh.ca. 2. Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. 3. Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Multimodal Imaging Group-Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo, Japan. 4. Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Multimodal Imaging Group-Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. 5. Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo, Japan. 6. Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo, Japan. 7. Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Multimodal Imaging Group-Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. 8. Multimodal Imaging Group-Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. 9. Department of Psychiatry, Faculties of Medicine and Health Science, University of Malta, Msida, Malta.
Abstract
OBJECTIVES: To assess the impact of reducing the dose of antipsychotics on cognition and dopaminergic D2 receptor availability in the whole striatum, and identify their relationship in patients with schizophrenia aged 50 years or older. DESIGN: Open-label prospective PET [11C]-raclopride study. SETTING: A tertiary care center outpatient setting. PARTICIPANTS: Thirty-seven clinically stable participants with schizophrenia or schizoaffective disorder, aged 50 years or greater, and having been treated with olanzapine or risperidone monotherapy at the same dose for at least 6 months. INTERVENTION: Gradual reduction in their olanzapine or risperidone daily dose of up to 40%. MEASUREMENTS: Clinical and cognitive assessments, and [11C]-raclopride PET to determine D2 receptor availability at baseline and after the dose reduction. Main outcome measures were overall cognition and D2 receptor availability in whole striatum. RESULTS: Reducing the antipsychotic dose resulted in an increase in D2 receptor availability in the whole striatum and an association between D2 receptor availability and overall cognition despite lack of change in the latter. There was also an association between change in D2 receptor availability and change in overall cognition. CONCLUSIONS: Our findings suggest that optimizing D2 receptor availability by reducing antipsychotic dose allows this system to contribute more significantly to cognitive function in patients with schizophrenia. This uncovered association could be harnessed by cognitive-enhancing interventions.
OBJECTIVES: To assess the impact of reducing the dose of antipsychotics on cognition and dopaminergic D2 receptor availability in the whole striatum, and identify their relationship in patients with schizophrenia aged 50 years or older. DESIGN: Open-label prospective PET [11C]-raclopride study. SETTING: A tertiary care center outpatient setting. PARTICIPANTS: Thirty-seven clinically stable participants with schizophrenia or schizoaffective disorder, aged 50 years or greater, and having been treated with olanzapine or risperidone monotherapy at the same dose for at least 6 months. INTERVENTION: Gradual reduction in their olanzapine or risperidone daily dose of up to 40%. MEASUREMENTS: Clinical and cognitive assessments, and [11C]-raclopride PET to determine D2 receptor availability at baseline and after the dose reduction. Main outcome measures were overall cognition and D2 receptor availability in whole striatum. RESULTS: Reducing the antipsychotic dose resulted in an increase in D2 receptor availability in the whole striatum and an association between D2 receptor availability and overall cognition despite lack of change in the latter. There was also an association between change in D2 receptor availability and change in overall cognition. CONCLUSIONS: Our findings suggest that optimizing D2 receptor availability by reducing antipsychotic dose allows this system to contribute more significantly to cognitive function in patients with schizophrenia. This uncovered association could be harnessed by cognitive-enhancing interventions.
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