@article{3f4a50d0463e4cf38d10451e1017edc3,
title = "Lack of association between dopaminergic antagonism and negative symptoms in schizophrenia: a positron emission tomography dopamine D2/3 receptor occupancy study",
abstract = "Rationale: Several pre-clinical studies suggest that antipsychotic medications cause secondary negative symptoms. However, direct evidence for a relationship among antipsychotic medications, their direct effects on neurotransmitter systems, and negative symptoms in schizophrenia remains controversial. Objective: The objective of this study was to examine the relationship between antipsychotic-related dopamine D2/3 receptor occupancy and negative symptoms in patients with schizophrenia. Methods: Forty-one clinically stable outpatients with schizophrenia participated in this prospective dose reduction positron emission tomography (PET) study. Clinical assessments and [11C]-raclopride PET scans were performed before and after participants underwent gradual dose reduction of their antipsychotic medication by up to 40 % from the baseline dose. Results: No significant relationship was found between antipsychotic-related dopamine D2/3 receptor occupancy and negative symptom severity at baseline or follow-up. Similar null findings were found for subdomains of negative symptoms (amotivation and diminished expression). Occupancy was significantly lower following dose reduction; however, negative symptom severity did not change significantly, though a trend toward reduction was noted. Examination of change scores between these two variables revealed no systematic relationship. Conclusions: Our cross-sectional and longitudinal results failed to find a significant dose-dependent relationship between severity of negative symptoms and antipsychotic-related dopaminergic antagonism in schizophrenia. These findings argue against the notion that antipsychotics necessarily cause secondary negative symptoms. Our results are also in contrast with the behavioral effects of dopaminergic antagonism routinely reported in pre-clinical investigations, suggesting that the role of this variable in the context of chronic treatment and schizophrenia needs to be re-examined.",
keywords = "Apathy, Dopamine, Extrapyramidal symptoms, Motivation, Negative symptoms, Schizophrenia, Side effects, Ventral striatum",
author = "Gagan Fervaha and Fernando Caravaggio and Mamo, {David C.} and Mulsant, {Benoit H.} and Pollock, {Bruce G.} and Shinichiro Nakajima and Philip Gerretsen and Rajji, {Tarek K.} and Wanna Mar and Yusuke Iwata and Eric Plitman and Chung, {Jun Ku} and Gary Remington and Ariel Graff-Guerrero",
note = "Funding Information: Dr. Gerretsen has received fellowship support from the CAMH Foundation, OMHF, and CIHR. Funding Information: Dr. Remington has received research support from the Schizophrenia Society of Ontario, CIHR, Research Hospital Fund—Canada Foundation for Innovation, Canadian Diabetes Association, Novartis Canada, Medicure Inc., and Neurocrine Bioscience; as a co-investigator, he has received research support from the Canadian Psychiatric Research Foundation and Pfizer Inc.; consultant fees from Laboratorios Farmac{\'e}uticos ROVI, Synchroneuron, Novartis, and Roche; and speaker{\textquoteright}s fees from Novartis. Funding Information: This work was funded by CIHR grant MOP-97946 (Dr. Graff-Guerrero), US National Institutes of Health grant RO1MH084886 (Dr. Graff-Guerrero), and a Vanier Canada Graduate Scholarship (Dr. Fervaha). Funding Information: Dr. Nakajima has received fellowship grants from the CIHR, Japan Society for the Promotion of Science, and Nakatomi Foundation and manuscript fees from Dainippon-Sumitomo Pharma and Kyowa Hakko Kirin. Funding Information: Dr. Rajji received research support from Brain Canada, Brain and Behavior Research Foundation, Canada Research Chair, Canadian Foundation for Innovation, CIHR, Ontario Ministry of Health and Long-Term Care, Ontario Ministry of Research and Innovation, the US NIH, and the W. Garfield Weston Foundation. Funding Information: Dr. Graff-Guerrero has received support from Brain Canada, Canadian Foundation for Innovation, CIHR, Ontario Ministry of Health and Long-Term Care, Ontario Ministry of Research and Innovation, the US National Institute of Health (NIH), Ontario Mental Health Foundation (OMHF), Consejo Nacional de Ciencia y Tecnologia (CONACyT), Instituto de Ciencia y Tecnolog{\'i}a del DF (ICyTDF), and Brain and Behavior Research Foundation. Funding Information: Dr. Mamo has received research support from Pfizer. Funding Information: Dr. Mulsant has received research support from Brain Canada, Centre for Addiction and Mental Health (CAMH) Foundation, CIHR, US NIH. He has also received medications for NIH-funded clinical trials from Bristol-Myers Squibb, Eli-Lilly and Company, and Pfizer. He directly own stocks of General Electric (<$5000). Publisher Copyright: {\textcopyright} 2016, Springer-Verlag Berlin Heidelberg.",
year = "2016",
month = oct,
day = "1",
doi = "10.1007/s00213-016-4415-6",
language = "English",
volume = "233",
pages = "3803--3813",
journal = "Psychopharmacology",
issn = "0033-3158",
publisher = "Springer Verlag",
number = "21-22",
}