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Transdiagnostic dimensions of symptoms and experiences associated with immune proteins in the continuity of psychosis

Published online by Cambridge University Press:  28 February 2024

Fabiana Corsi-Zuelli Open the ORCID record for Fabiana Corsi-Zuelli [Opens in a new window] ,
Diego Quattrone Open the ORCID record for Diego Quattrone [Opens in a new window] ,
Taciana Cristina Carvalho Ragazzi ,
Camila Marcelino Loureiro ,
Rosana Shuhama ,
Paulo Rossi Menezes ,
Paulo Louzada-Junior  and
Cristina Marta Del-Ben
Fabiana Corsi-Zuelli*
Affiliation:
Department of Neuroscience and Behaviour, University of São Paulo, Ribeirão Preto Medical School, São Paulo, Brazil Center for Research on Inflammatory Diseases – CRID, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
Diego Quattrone
Affiliation:
Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK
Taciana Cristina Carvalho Ragazzi
Affiliation:
Department of Neuroscience and Behaviour, University of São Paulo, Ribeirão Preto Medical School, São Paulo, Brazil
Camila Marcelino Loureiro
Affiliation:
Department of Neuroscience and Behaviour, University of São Paulo, Ribeirão Preto Medical School, São Paulo, Brazil
Rosana Shuhama
Affiliation:
Department of Neuroscience and Behaviour, University of São Paulo, Ribeirão Preto Medical School, São Paulo, Brazil
Paulo Rossi Menezes
Affiliation:
Department of Preventive Medicine, University of São Paulo, Faculty of Medicine, São Paulo, Brazil
Paulo Louzada-Junior
Affiliation:
Center for Research on Inflammatory Diseases – CRID, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil Department of Internal Medicine, University of São Paulo, Ribeirão Preto Medical School, São Paulo, Brazil
Cristina Marta Del-Ben
Affiliation:
Department of Neuroscience and Behaviour, University of São Paulo, Ribeirão Preto Medical School, São Paulo, Brazil
*
Corresponding author: Fabiana Corsi-Zuelli; Email: fabiana.zuelli@usp.br
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Abstract

Background

There is limited evidence as to whether the immune protein profile is associated with a particular symptomatology pattern across the psychosis continuum.

Methods

We estimated two bifactor models of general and specific dimensions of psychotic experiences in unaffected siblings of patients (n = 52) and community controls (n = 200), and of psychotic symptoms in first-episode psychosis (FEP) patients (n = 110). We evaluated associations between these transdiagnostic dimensions and trait (TNF-α, IFN-γ), state (IL-6, IL-1β), and regulatory (TGF-β, IL-10, IL-4) cytokines. We explored whether schizophrenia genetic liability (schizophrenia polygenic risk score; SZ-PRS) modified the associations.

Results

High levels of trait marker IFN-γ were associated with the severity of general psychosis dimension in the unaffected siblings and community controls, expanding to the depressive dimension in siblings and to the manic dimension in FEP. High TNF-α levels were associated with more positive psychotic experiences in unaffected siblings and manic symptoms in FEP. Low levels of state markers IL-6 and IL-1β were observed in unaffected siblings presenting more depressive experiences. Still, high levels of IL-6 and IL-1β were associated with the severity of the depressive and negative symptom dimensions at FEP. The severity of transdiagnostic dimension scores across the three groups was associated with lower regulatory cytokines. Exploratory analysis suggested that a high SZ-PRS contributed mostly to associations with psychotic dimensions.

Conclusions

IFN-γ mapped onto the multidimensional expression of psychosis, reinforcing the trait concept. State markers IL-6 and IL-1β may fluctuate along the spectrum. Dysfunction in the regulatory arm may disinhibit the inflammatory system. Associations with psychotic dimensions may be more prone to SZ-PRS susceptibility.

Keywords

inflammationpsychosis continuumpsychotic experiencesschizophreniasiblings
Type
Original Article
Information
Psychological Medicine , First View , pp. 1 - 13
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Copyright
Copyright © The Author(s), 2024. Published by Cambridge University Press

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