TY - JOUR
T1 - Cognition and Dopamine D2 Receptor Availability in the Striatum in Older Patients with Schizophrenia
AU - Rajji, Tarek K.
AU - Mulsant, Benoit H.
AU - Nakajima, Shinichiro
AU - Caravaggio, Fernando
AU - Suzuki, Takefumi
AU - Uchida, Hiroyuki
AU - Gerretsen, Philip
AU - Mar, Wanna
AU - Pollock, Bruce G.
AU - Mamo, David C.
AU - Graff-Guerrero, Ariel
N1 - Funding Information:
Dr. Rajji receives research support from Brain Canada , Brain and Behavior Research Foundation , CAMH Foundation , a Canada Research Chair in Neurostimulation for Cognitive Disorders , Canada Foundation for Innovation (CFI), Canadian Institutes of Health Research (CIHR), Ontario Ministry of Health and Long-Term Care , Ontario Ministry of Research and Innovation , the U.S. National Institute of Health (NIH), and the W. Garfield Weston Foundation . Dr. Rajji reports no competing interests. Dr. Mulsant receives research support from Brain Canada, CAMH Foundation, CFI, CIHR, and NIH. During the past 5 years, he has received medications for NIH-funded clinical trials from Bristol-Myers Squibb, Eli Lilly, and Pfizer. He directly own stocks of General Electric (less than $5,000). Dr. Nakajima has received fellowship grants from CIHR, Japan Society for the Promotion of Science , and Nakatomi Foundation , and manuscript fees from Dainippon Sumitomo Pharma and Kyowa Hakko Kirin . Dr. Suzuki has received manuscript and speaker's fees from Astellas , Dainippon Sumitomo , Eli Lilly , Elsevier Japan , Janssen , Meiji Seika Pharma , Otsuka , and Weily Japan . Dr. Uchida has received grants from Astellas Pharmaceutical, Eisai , Otsuka Pharmaceutical , GlaxoSmithKline , Shionogi , Dainippon-Sumitomo Pharma, Eli Lilly, Mochida Pharmaceutical Company , Meiji Seika Pharma, and Yoshitomi Yakuhin , and speaker's honoraria from Otsuka Pharmaceutical, Eli Lilly, Shionogi, GlaxoSmithKline, Yoshitomi Yakuhin, Dainippon-Sumitomo Pharma, Meiji Seika Pharma, AbbVie , MSD , and Janssen Pharmaceutical within the past 2 years. Dr. Pollock has received support from Brain Canada, CAMH Foundation, CIHR, and NIH. He was also a faculty member of the Lundbeck International Neuroscience Foundation (LINF) (final meeting was April 2010). Dr. Graff-Guerrero has received support from Brain Canada, Brain and Behavior Research Foundation, CFI, CIHR, NIH, Ontario Ministry of Health and Long-Term Care, Ontario Ministry of Research and Innovation, Ontario Mental Health Foundation (OMHF), Consejo Nacional de Ciencia y Tecnología (CONACyT), Instituto de Ciencia y Tecnología del Distrito Federal (ICyTDF).
Funding Information:
This work was partially supported by Canadian Institutes of Health Research (grant MOP-9794 to DCM) and the National Institutes of Health (grant R01MH084886-01A2 to DCM).
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
AB - 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.
KW - D receptor
KW - PET
KW - antipsychotic
KW - cognition
KW - late-life schizophrenia
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UR - http://www.scopus.com/inward/citedby.url?scp=84994403358&partnerID=8YFLogxK
U2 - 10.1016/j.jagp.2016.08.001
DO - 10.1016/j.jagp.2016.08.001
M3 - Article
C2 - 27745822
AN - SCOPUS:84994403358
VL - 25
SP - 1
EP - 10
JO - American Journal of Geriatric Psychiatry
JF - American Journal of Geriatric Psychiatry
SN - 1064-7481
IS - 1
ER -