The effects of illness severity, cognition, and estimated antipsychotic dopamine receptor occupancy on insight into the illness in schizophrenia: An analysis of clinical antipsychotic trials of intervention effectiveness (CATIE) data

Miracle Ozzoude, Shinichiro Nakajima, Eric Plitman, Jun Ku Chung, Julia Kim, Yusuke Iwata, Fernando Caravaggio, Hiroyoshi Takeuchi, Hiroyuki Uchida, Ariel Graff-Guerrero, Philip Gerretsen

Research output: Contribution to journalArticle

Abstract

Background: The relationship between dopamine D2 receptor (D2R) occupancy and impaired illness awareness (IIA) remains unclear. While IIA is associated with illness severity and cognitive dysfunction, antipsychotic medication, the principal treatment for schizophrenia, indirectly improves IIA, but may simultaneously contribute to cognitive dysfunction at supratherapeutic doses. Aim and methods: We investigated the influence of estimated D2R (Est.D2R) occupancy by antipsychotics on the relationships between IIA and illness severity, and IIA and cognition. IIA was assessed in 373 adult patients with schizophrenia (18−62 years) using data from CATIE. IIA was measured using the Positive and Negative Syndrome Scale (PANSS) item G12. D2R occupancy levels were estimated from plasma concentrations for risperidone, olanzapine, and ziprasidone. Correlation, regression, and path analyses were performed to examine IIA's relationship to illness severity, cognition, and Est.D2R. Results: Illness severity was predictive of IIA. However, premorbid IQ, cognition, and Est.D2R did not predict IIA, and Est.D2R did not serve either a moderating or mediating role in both regression and path analyses. Conclusions: Consistent with previous literature, our results suggest that IIA is a function of illness severity in adult patients with schizophrenia. Future studies should explore whether D2R occupancy mediates the relationships between IIA and illness severity, and IIA and cognitive dysfunction, in late-life schizophrenia (i.e. ≥60 years) given the effects of aging on cognition, IIA, and antipsychotic sensitivity.

LanguageEnglish
Pages207-213
Number of pages7
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Volume89
DOIs
Publication statusPublished - 2019 Mar 8

Fingerprint

Dopamine Receptors
Cognition
Antipsychotic Agents
Schizophrenia
Clinical Trials
olanzapine
Regression Analysis
Risperidone
Dopamine D2 Receptors

Keywords

  • D receptor occupancy
  • Illness severity, Cognition
  • Insight into illness
  • Schizophrenia
  • Structural Equation Modeling

ASJC Scopus subject areas

  • Pharmacology
  • Biological Psychiatry

Cite this

@article{1bd7a3467345404abd8935185eb4f8c6,
title = "The effects of illness severity, cognition, and estimated antipsychotic dopamine receptor occupancy on insight into the illness in schizophrenia: An analysis of clinical antipsychotic trials of intervention effectiveness (CATIE) data",
abstract = "Background: The relationship between dopamine D2 receptor (D2R) occupancy and impaired illness awareness (IIA) remains unclear. While IIA is associated with illness severity and cognitive dysfunction, antipsychotic medication, the principal treatment for schizophrenia, indirectly improves IIA, but may simultaneously contribute to cognitive dysfunction at supratherapeutic doses. Aim and methods: We investigated the influence of estimated D2R (Est.D2R) occupancy by antipsychotics on the relationships between IIA and illness severity, and IIA and cognition. IIA was assessed in 373 adult patients with schizophrenia (18−62 years) using data from CATIE. IIA was measured using the Positive and Negative Syndrome Scale (PANSS) item G12. D2R occupancy levels were estimated from plasma concentrations for risperidone, olanzapine, and ziprasidone. Correlation, regression, and path analyses were performed to examine IIA's relationship to illness severity, cognition, and Est.D2R. Results: Illness severity was predictive of IIA. However, premorbid IQ, cognition, and Est.D2R did not predict IIA, and Est.D2R did not serve either a moderating or mediating role in both regression and path analyses. Conclusions: Consistent with previous literature, our results suggest that IIA is a function of illness severity in adult patients with schizophrenia. Future studies should explore whether D2R occupancy mediates the relationships between IIA and illness severity, and IIA and cognitive dysfunction, in late-life schizophrenia (i.e. ≥60 years) given the effects of aging on cognition, IIA, and antipsychotic sensitivity.",
keywords = "D receptor occupancy, Illness severity, Cognition, Insight into illness, Schizophrenia, Structural Equation Modeling",
author = "Miracle Ozzoude and Shinichiro Nakajima and Eric Plitman and Chung, {Jun Ku} and Julia Kim and Yusuke Iwata and Fernando Caravaggio and Hiroyoshi Takeuchi and Hiroyuki Uchida and Ariel Graff-Guerrero and Philip Gerretsen",
year = "2019",
month = "3",
day = "8",
doi = "10.1016/j.pnpbp.2018.08.033",
language = "English",
volume = "89",
pages = "207--213",
journal = "Progress in Neuro-Psychopharmacology and Biological Psychiatry",
issn = "0278-5846",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - The effects of illness severity, cognition, and estimated antipsychotic dopamine receptor occupancy on insight into the illness in schizophrenia

T2 - Progress in Neuro-Psychopharmacology and Biological Psychiatry

AU - Ozzoude, Miracle

AU - Nakajima, Shinichiro

AU - Plitman, Eric

AU - Chung, Jun Ku

AU - Kim, Julia

AU - Iwata, Yusuke

AU - Caravaggio, Fernando

AU - Takeuchi, Hiroyoshi

AU - Uchida, Hiroyuki

AU - Graff-Guerrero, Ariel

AU - Gerretsen, Philip

PY - 2019/3/8

Y1 - 2019/3/8

N2 - Background: The relationship between dopamine D2 receptor (D2R) occupancy and impaired illness awareness (IIA) remains unclear. While IIA is associated with illness severity and cognitive dysfunction, antipsychotic medication, the principal treatment for schizophrenia, indirectly improves IIA, but may simultaneously contribute to cognitive dysfunction at supratherapeutic doses. Aim and methods: We investigated the influence of estimated D2R (Est.D2R) occupancy by antipsychotics on the relationships between IIA and illness severity, and IIA and cognition. IIA was assessed in 373 adult patients with schizophrenia (18−62 years) using data from CATIE. IIA was measured using the Positive and Negative Syndrome Scale (PANSS) item G12. D2R occupancy levels were estimated from plasma concentrations for risperidone, olanzapine, and ziprasidone. Correlation, regression, and path analyses were performed to examine IIA's relationship to illness severity, cognition, and Est.D2R. Results: Illness severity was predictive of IIA. However, premorbid IQ, cognition, and Est.D2R did not predict IIA, and Est.D2R did not serve either a moderating or mediating role in both regression and path analyses. Conclusions: Consistent with previous literature, our results suggest that IIA is a function of illness severity in adult patients with schizophrenia. Future studies should explore whether D2R occupancy mediates the relationships between IIA and illness severity, and IIA and cognitive dysfunction, in late-life schizophrenia (i.e. ≥60 years) given the effects of aging on cognition, IIA, and antipsychotic sensitivity.

AB - Background: The relationship between dopamine D2 receptor (D2R) occupancy and impaired illness awareness (IIA) remains unclear. While IIA is associated with illness severity and cognitive dysfunction, antipsychotic medication, the principal treatment for schizophrenia, indirectly improves IIA, but may simultaneously contribute to cognitive dysfunction at supratherapeutic doses. Aim and methods: We investigated the influence of estimated D2R (Est.D2R) occupancy by antipsychotics on the relationships between IIA and illness severity, and IIA and cognition. IIA was assessed in 373 adult patients with schizophrenia (18−62 years) using data from CATIE. IIA was measured using the Positive and Negative Syndrome Scale (PANSS) item G12. D2R occupancy levels were estimated from plasma concentrations for risperidone, olanzapine, and ziprasidone. Correlation, regression, and path analyses were performed to examine IIA's relationship to illness severity, cognition, and Est.D2R. Results: Illness severity was predictive of IIA. However, premorbid IQ, cognition, and Est.D2R did not predict IIA, and Est.D2R did not serve either a moderating or mediating role in both regression and path analyses. Conclusions: Consistent with previous literature, our results suggest that IIA is a function of illness severity in adult patients with schizophrenia. Future studies should explore whether D2R occupancy mediates the relationships between IIA and illness severity, and IIA and cognitive dysfunction, in late-life schizophrenia (i.e. ≥60 years) given the effects of aging on cognition, IIA, and antipsychotic sensitivity.

KW - D receptor occupancy

KW - Illness severity, Cognition

KW - Insight into illness

KW - Schizophrenia

KW - Structural Equation Modeling

UR - http://www.scopus.com/inward/record.url?scp=85053447457&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85053447457&partnerID=8YFLogxK

U2 - 10.1016/j.pnpbp.2018.08.033

DO - 10.1016/j.pnpbp.2018.08.033

M3 - Article

VL - 89

SP - 207

EP - 213

JO - Progress in Neuro-Psychopharmacology and Biological Psychiatry

JF - Progress in Neuro-Psychopharmacology and Biological Psychiatry

SN - 0278-5846

ER -