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The role of psychosis and clozapine load in excessive checking in treatment-resistant schizophrenia: longitudinal observational study.

Published version
Peer-reviewed

Repository DOI


Type

Article

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Authors

Fernandez-Egea, Emilio  ORCID logo  https://orcid.org/0000-0003-4128-8955
Sangüesa, Estela 
Gassó, Patricia 
Biria, Marjan 

Abstract

BACKGROUND: A significant proportion of people with clozapine-treated schizophrenia develop 'checking' compulsions, a phenomenon yet to be understood. AIMS: To use habit formation models developed in cognitive neuroscience to investigate the dynamic interplay between psychosis, clozapine dose and obsessive-compulsive symptoms (OCS). METHOD: Using the anonymised electronic records of a cohort of clozapine-treated patients, including longitudinal assessments of OCS and psychosis, we performed longitudinal multi-level mediation and multi-level moderation analyses to explore associations of psychosis with obsessiveness and excessive checking. Classic bivariate correlation tests were used to assess clozapine load and checking compulsions. The influence of specific genetic variants was tested in a subsample. RESULTS: A total of 196 clozapine-treated individuals and 459 face-to-face assessments were included. We found significant OCS to be common (37.9%), with checking being the most prevalent symptom. In mediation models, psychosis severity mediated checking behaviour indirectly by inducing obsessions (r = 0.07, 95% CI 0.04-0.09; P < 0.001). No direct effect of psychosis on checking was identified (r = -0.28, 95% CI -0.09 to 0.03; P = 0.340). After psychosis remission (n = 65), checking compulsions correlated with both clozapine plasma levels (r = 0.35; P = 0.004) and dose (r = 0.38; P = 0.002). None of the glutamatergic and serotonergic genetic variants were found to moderate the effect of psychosis on obsession and compulsion (SLC6A4, SLC1A1 and HTR2C) survived the multiple comparisons correction. CONCLUSIONS: We elucidated different phases of the complex interplay of psychosis and compulsions, which may inform clinicians' therapeutic decisions.

Description

Keywords

Habit formation, clozapine, compulsion, serotonin, treatment-resistant schizophrenia, Humans, Clozapine, Male, Female, Adult, Antipsychotic Agents, Longitudinal Studies, Psychotic Disorders, Schizophrenia, Treatment-Resistant, Middle Aged, Compulsive Behavior, Obsessive-Compulsive Disorder, Schizophrenia

Journal Title

Br J Psychiatry

Conference Name

Journal ISSN

0007-1250
1472-1465

Volume Title

224

Publisher

Royal College of Psychiatrists
Sponsorship
MRC (MR/W029987/1)
Medical Research Council (MC_PC_17213)
MRC (via Swansea University) (DATAMIND 106893)
National Institute for Health and Care Research (IS-BRC-1215-20014)
Medical Research Council (MR/W014386/1)
Medical Research Council (MR/W029987/1)
An intramural research award from Universidad San Jorge supported ES. MB, IJB, and NS were supported by a studentship from the Mental Health Research UK. SC’s and RNC’s research was funded by the UK Medical Research Council (grant MC_PC_19213, MR/W014386/1). Dr. Fernandez-Egea is supported by the 2022 MRC/NIHR CARP award (MR/W029987/1), and this research was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014, NIHR203312). The views expressed are those of the author(s) and not necessarily of the NIHR or the Department of Health and Social Care.