Insight into illness and its relationship to illness severity, cognition and estimated antipsychotic dopamine receptor occupancy in schizophrenia: An antipsychotic dose reduction study

Little is known about the influence of D₂ receptor occupancy on impaired insight into illness (III)—a core feature of schizophrenia. III is associated with illness severity and cognitive dysfunction. Comparably, supratherapeutic D₂ receptor occupancy can impair cognition. However, it is unclear how illness severity, cognition, and D₂ receptor 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 D₂ receptor occupancy (Est.D₂). Cognition and Est.D₂ predicted III at baseline. At 28 weeks post-reduction, illness severity and Est.D₂ predicted III. Our findings suggest a complex relationship may exist among III, illness severity, cognition and Est.D₂. At higher D₂ receptor occupancies, III is influenced by cognitive dysfunction, whereas, at lower occupancies, illness severity has a stronger effect on III.