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

Psychiatry Res. 2017 May:251:20-25. doi: 10.1016/j.psychres.2017.01.090. Epub 2017 Feb 1.


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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / therapeutic use*
  • Cognition / physiology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Problem Solving / physiology
  • Receptors, Dopamine D2 / metabolism*
  • Schizophrenia / diagnosis
  • Schizophrenia / drug therapy*
  • Schizophrenia / metabolism
  • Schizophrenic Psychology
  • Severity of Illness Index


  • Antipsychotic Agents
  • Receptors, Dopamine D2