title: Insight into illness and its relationship to illness severity, cognition and estimated antipsychotic dopamine receptor occupancy in schizophrenia: An antipsychotic dose reduction study.
abstract: Little is known about the influence of D2receptor occupancy on impaired insight into illness (III)-a core feature of schizophrenia. III is associated with illness severity and cognitive dysfunction. Comparably, supratherapeutic D2receptor occupancy can impair cognition. However, it is unclear how illness severity, cognition, and D2receptor occupancy interact to influence III in schizophrenia. The aim of this study was to explore the influence of antipsychotic dose reduction on the relationships of illness severity and cognition to III. III was assessed at baseline and 28 weeks post-antipsychotic dose reduction in 16 participants with schizophrenia and plasma antipsychotic concentrations. III was assessed primarily with the Schedule for the Assessment of Insight-Japanese version, and secondarily with the Positive and Negative Syndrome Scale item G12. Correlation and regression analyses were performed to explore III's relationship to illness severity, cognition, and estimated D2receptor occupancy (Est.D2). Cognition and Est.D2predicted III at baseline. At 28 weeks post-reduction, illness severity and Est.D2predicted III. Our findings suggest a complex relationship may exist among III, illness severity, cognition and Est.D2. At higher D2receptor occupancies, III is influenced by cognitive dysfunction, whereas, at lower occupancies, illness severity has a stronger effect on III.
authors.affiliation: Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; University of Toronto, Toronto, Ontario, Canada; Geriatric Mental Health Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Multimodal Imaging Group - Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. Electronic address: philgerretsen@yahoo.com.
authors.forename: Philip
authors.initials: P
authors.lastname: Gerretsen
authors.affiliation: University of Toronto, Toronto, Ontario, Canada; Schizophrenia Division, Complex Mental Illness Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Takeuchi
authors.affiliation: University of Toronto, Toronto, Ontario, Canada; Multimodal Imaging Group - Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Miracle
authors.initials: M
authors.lastname: Ozzoude
authors.affiliation: Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; University of Toronto, Toronto, Ontario, Canada; Geriatric Mental Health Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Multimodal Imaging Group - Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Ariel
authors.initials: A
authors.lastname: Graff-Guerrero
authors.affiliation: Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; Geriatric Mental Health Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Uchida
mesh_terms: D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003071:Cognition / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011340:Problem Solving / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D012565:Schizophrenic Psychology; D012720:Severity of Illness Index
chemical_list: D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2