Background Obsessive-compulsive symptoms (OCS) emerge in a significant proportion of clozapine-treated schizophrenia patients, affecting social functioning and increasing depressive symptoms. This study investigates the underexplored cognitive mechanisms of clozapine-induced OCS, particularly focusing on dysfunctional checking behavior. Methods Clinical and cognitive profiles of OCS and their relationship to dysfunctional checking were investigated using a novel checking paradigm (image verification task or IVT) in four groups: clozapine-treated schizophrenia patients with clozapine-induced OCS (SCZ-OCS, n = 21) and without (SCZ-only, n = 15), patients with obsessive-compulsive disorder (OCD, n = 32) and IQ-matched healthy volunteers (HV, n = 30). Results Only SCZ-OCS patients showed a distinctive pattern of dysfunctional checking on the IVT. Compared with SCZ-OCS, SCZ-only patients exhibited functional checking while having equivalent deficits in executive cognition, clozapine dose, and treatment duration, though with less severe positive and depressive symptoms. In SCZ-OCS, dysfunctional checking was positively correlated with clozapine dose and working memory performance. By contrast, OCD patients’ checking was positively related to intolerance of uncertainty. Checking in the OCD and SCZ-OCS groups was positively correlated with YBOCS-compulsion. Conclusion This study is the first to compare the distinct cognitive and clinical profiles of SCZ-OCS, SCZ-only, and OCD, with a focus on checking behavior, a major symptom in clozapine-treated patients. We introduced a novel and sensitive measure for checking, which showed dysfunctional checking only in SCZ-OCS patients treated with clozapine. These findings indicate that a subset of patients with schizophrenia with more severe positive symptoms and cognitive deficits are especially susceptible to OCD symptoms when treated with clozapine.
Clozapine-induced obsessive-compulsive symptoms in schizophrenia: Clinical and cognitive determinants of dysfunctional checking
Marjan Biria,P. Banca,I. J. Barnham,Aleya A. Marzuki,Nuria Segarra,Engin Keser,A. Sule,M. Farrugia,Qiang Luo,N. Fineberg,E. Fernandez-Egea,T. W. Robbins
Published 2025 in Psychological Medicine
ABSTRACT
PUBLICATION RECORD
- Publication year
2025
- Venue
Psychological Medicine
- Publication date
2025-03-18
- Fields of study
Medicine, Psychology
- Identifiers
- External record
- Source metadata
Semantic Scholar, PubMed
CITATION MAP
EXTRACTION MAP
CLAIMS
- No claims are published for this paper.
CONCEPTS
- No concepts are published for this paper.
REFERENCES
Showing 1-57 of 57 references · Page 1 of 1
CITED BY
Showing 1-3 of 3 citing papers · Page 1 of 1