Peripheral inflammation and neurocognitive functioning in early psychosis: Specific associations of TNF-α and IL-6 with social cognition
Abstract Background Cognitive deficits and immune system dysregulation are core features of psychotic disorders. Among inflammatory markers, interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) have been linked to both psychosis pathophysiology and related cognitive impairments. Methods We...
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Cambridge University Press
2025-01-01
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| Series: | European Psychiatry |
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| Online Access: | https://www.cambridge.org/core/product/identifier/S0924933825100631/type/journal_article |
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| author | Ana Catalán Claudia Aymerich José Manuel Rodríguez-Sánchez Borja Pedruzo Gonzalo Salazar de Pablo Patxi Gil Francisco Aguayo Garazi Acasuso Alvaro Collado-Pérez Javier Goena Olatz Ibarretxe Iñaki Zorrilla Ana González-Pinto Leire Erkoreka Daniel Alonso-Alconada Paolo Fusar-Poli Miguel Angel González-Torres |
| author_facet | Ana Catalán Claudia Aymerich José Manuel Rodríguez-Sánchez Borja Pedruzo Gonzalo Salazar de Pablo Patxi Gil Francisco Aguayo Garazi Acasuso Alvaro Collado-Pérez Javier Goena Olatz Ibarretxe Iñaki Zorrilla Ana González-Pinto Leire Erkoreka Daniel Alonso-Alconada Paolo Fusar-Poli Miguel Angel González-Torres |
| author_sort | Ana Catalán |
| collection | DOAJ |
| description | Abstract
Background
Cognitive deficits and immune system dysregulation are core features of psychotic disorders. Among inflammatory markers, interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) have been linked to both psychosis pathophysiology and related cognitive impairments.
Methods
We investigated associations among IL-6, TNF-α, and neurocognitive performance in 107 participants: individuals at clinical high risk for psychosis (CHR-P, n = 35), first-episode psychosis (FEP, n = 39), and healthy controls (HC, n = 33). Assessments included memory, processing speed, executive function, and social cognition. Cytokines were measured from fasting serum samples. Analyses included ANOVA, correlations, and multivariate regressions controlling for age, sex, IQ, group, and symptom severity.
Results
TNF-α levels were significantly elevated in FEP compared to CHR-P (p = 0.0251); IL-6 differences were non-significant. FEP showed poorer performance in multiple cognitive domains, especially social cognition. CHR-P individuals exhibited intermediate profiles between FEP and HC in cognition. In adjusted regression models, IL-6 was significantly associated with undermentalization on the MASC task (β = 0.28, p = 0.0337) and showed a trend-level association with slower processing speed (β = 0.98, p = 0.075). TNF-α levels predicted poorer facial emotion recognition (β = −1.37, p = 0.0022). IQ and group were significant covariates in most models.
Conclusions
Our findings suggest that peripheral inflammation, particularly IL-6 and TNF-α, may selectively impact social cognitive functioning in early psychosis. Though modest, these associations highlight potential inflammatory contributions to functional impairment and support further investigation of immunological targets in early intervention.
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| format | Article |
| id | doaj-art-8dcb1f4908cf42dbb5feb6d2218d39b7 |
| institution | Kabale University |
| issn | 0924-9338 1778-3585 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Cambridge University Press |
| record_format | Article |
| series | European Psychiatry |
| spelling | doaj-art-8dcb1f4908cf42dbb5feb6d2218d39b72025-08-20T03:55:48ZengCambridge University PressEuropean Psychiatry0924-93381778-35852025-01-016810.1192/j.eurpsy.2025.10063Peripheral inflammation and neurocognitive functioning in early psychosis: Specific associations of TNF-α and IL-6 with social cognitionAna Catalán0https://orcid.org/0000-0002-0418-7904Claudia Aymerich1https://orcid.org/0000-0003-0040-1608José Manuel Rodríguez-Sánchez2Borja Pedruzo3https://orcid.org/0000-0003-1460-1571Gonzalo Salazar de Pablo4Patxi Gil5https://orcid.org/0000-0001-7438-9248Francisco Aguayo6Garazi Acasuso7https://orcid.org/0009-0006-6676-7097Alvaro Collado-Pérez8Javier Goena9https://orcid.org/0000-0002-7786-4187Olatz Ibarretxe10https://orcid.org/0009-0008-7192-5680Iñaki Zorrilla11https://orcid.org/0000-0001-6444-8208Ana González-Pinto12Leire Erkoreka13Daniel Alonso-Alconada14https://orcid.org/0000-0002-9874-2947Paolo Fusar-Poli15Miguel Angel González-Torres16Department of Neuroscience, University of the Basque Country UPV/EHU, Leioa, Spain Department of Psychiatry, Basurto University Hospital, OSI Bilbao-Basurto, Bilbao, Spain Early Psychosis: Interventions and Clinical-Detection (EPIC) Lab, Department of Psychosis Studies, King’s College London, London, UK Neurosciences, Biobizkaia Health Research Institute, Bizkaia, Spain Spanish Network for Research in Mental Health, Carlos III Institute (CIBERSAM, ISCIII), Madrid, SpainSpanish Network for Research in Mental Health, Carlos III Institute (CIBERSAM, ISCIII), Madrid, Spain Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK Child and Adolescent Mental Health Services, South London and Maudsley NHS Foundation Trust, London, UK.Osakidetza, Basque Health Service, Bizkaia Mental Health Service, Lehenak Program, Bilbao, SpainDepartment of Neuroscience, University of the Basque Country UPV/EHU, Leioa, Spain Department of Psychiatry, Basurto University Hospital, OSI Bilbao-Basurto, Bilbao, Spain Neurosciences, Biobizkaia Health Research Institute, Bizkaia, Spain Spanish Network for Research in Mental Health, Carlos III Institute (CIBERSAM, ISCIII), Madrid, SpainSpanish Network for Research in Mental Health, Carlos III Institute (CIBERSAM, ISCIII), Madrid, Spain Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK Child and Adolescent Mental Health Services, South London and Maudsley NHS Foundation Trust, London, UK. Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón School of Medicine, Universidad Complutense, Madrid, SpainOsakidetza, Basque Health Service, Bizkaia Mental Health Service, Lehenak Program, Bilbao, SpainDepartment of Laboratory Medicine, Basurto University Hospital, OSI Bilbao-Basurto, Bilbao, SpainNeurosciences, Biobizkaia Health Research Institute, Bizkaia, SpainDepartment of Laboratory Medicine, Basurto University Hospital, OSI Bilbao-Basurto, Bilbao, SpainDepartment of Psychiatry, Basurto University Hospital, OSI Bilbao-Basurto, Bilbao, Spain Neurosciences, Biobizkaia Health Research Institute, Bizkaia, SpainDepartment of Neuroscience, University of the Basque Country UPV/EHU, Leioa, SpainDepartment of Neuroscience, University of the Basque Country UPV/EHU, Leioa, Spain Spanish Network for Research in Mental Health, Carlos III Institute (CIBERSAM, ISCIII), Madrid, Spain Psychiatry Service, Basque Country Health Service (Osakidetza), Araba University Hospital, Vitoria-Gasteiz, Spain Neurosciences, BioAraba, Health Research Institute, Vitoria-Gasteiz, SpainDepartment of Neuroscience, University of the Basque Country UPV/EHU, Leioa, Spain Spanish Network for Research in Mental Health, Carlos III Institute (CIBERSAM, ISCIII), Madrid, Spain Psychiatry Service, Basque Country Health Service (Osakidetza), Araba University Hospital, Vitoria-Gasteiz, Spain Neurosciences, BioAraba, Health Research Institute, Vitoria-Gasteiz, SpainDepartment of Neuroscience, University of the Basque Country UPV/EHU, Leioa, Spain Neurosciences, Biobizkaia Health Research Institute, Bizkaia, Spain Spanish Network for Research in Mental Health, Carlos III Institute (CIBERSAM, ISCIII), Madrid, Spain Galdakao-Usansolo University Hospital, Osakidetza Basque Health Service, Galdakao, SpainDepartment of Cell Biology and Histology, School of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, SpainEarly Psychosis: Interventions and Clinical-Detection (EPIC) Lab, Department of Psychosis Studies, King’s College London, London, UK Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy Outreach and Support in South-London (OASIS) service, South London and Maudlsey (SLaM) NHS Foundation Trust, London, UK Department of Psychiatry and Psychotherapy, University Hospital, Ludwig-Maximilian-University (LMU), Munich, GermanyDepartment of Neuroscience, University of the Basque Country UPV/EHU, Leioa, Spain Department of Psychiatry, Basurto University Hospital, OSI Bilbao-Basurto, Bilbao, Spain Neurosciences, Biobizkaia Health Research Institute, Bizkaia, Spain Spanish Network for Research in Mental Health, Carlos III Institute (CIBERSAM, ISCIII), Madrid, SpainAbstract Background Cognitive deficits and immune system dysregulation are core features of psychotic disorders. Among inflammatory markers, interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) have been linked to both psychosis pathophysiology and related cognitive impairments. Methods We investigated associations among IL-6, TNF-α, and neurocognitive performance in 107 participants: individuals at clinical high risk for psychosis (CHR-P, n = 35), first-episode psychosis (FEP, n = 39), and healthy controls (HC, n = 33). Assessments included memory, processing speed, executive function, and social cognition. Cytokines were measured from fasting serum samples. Analyses included ANOVA, correlations, and multivariate regressions controlling for age, sex, IQ, group, and symptom severity. Results TNF-α levels were significantly elevated in FEP compared to CHR-P (p = 0.0251); IL-6 differences were non-significant. FEP showed poorer performance in multiple cognitive domains, especially social cognition. CHR-P individuals exhibited intermediate profiles between FEP and HC in cognition. In adjusted regression models, IL-6 was significantly associated with undermentalization on the MASC task (β = 0.28, p = 0.0337) and showed a trend-level association with slower processing speed (β = 0.98, p = 0.075). TNF-α levels predicted poorer facial emotion recognition (β = −1.37, p = 0.0022). IQ and group were significant covariates in most models. Conclusions Our findings suggest that peripheral inflammation, particularly IL-6 and TNF-α, may selectively impact social cognitive functioning in early psychosis. Though modest, these associations highlight potential inflammatory contributions to functional impairment and support further investigation of immunological targets in early intervention. https://www.cambridge.org/core/product/identifier/S0924933825100631/type/journal_articleclinical high riskIL-6psychosisschizophreniaTNF-α |
| spellingShingle | Ana Catalán Claudia Aymerich José Manuel Rodríguez-Sánchez Borja Pedruzo Gonzalo Salazar de Pablo Patxi Gil Francisco Aguayo Garazi Acasuso Alvaro Collado-Pérez Javier Goena Olatz Ibarretxe Iñaki Zorrilla Ana González-Pinto Leire Erkoreka Daniel Alonso-Alconada Paolo Fusar-Poli Miguel Angel González-Torres Peripheral inflammation and neurocognitive functioning in early psychosis: Specific associations of TNF-α and IL-6 with social cognition European Psychiatry clinical high risk IL-6 psychosis schizophrenia TNF-α |
| title | Peripheral inflammation and neurocognitive functioning in early psychosis: Specific associations of TNF-α and IL-6 with social cognition |
| title_full | Peripheral inflammation and neurocognitive functioning in early psychosis: Specific associations of TNF-α and IL-6 with social cognition |
| title_fullStr | Peripheral inflammation and neurocognitive functioning in early psychosis: Specific associations of TNF-α and IL-6 with social cognition |
| title_full_unstemmed | Peripheral inflammation and neurocognitive functioning in early psychosis: Specific associations of TNF-α and IL-6 with social cognition |
| title_short | Peripheral inflammation and neurocognitive functioning in early psychosis: Specific associations of TNF-α and IL-6 with social cognition |
| title_sort | peripheral inflammation and neurocognitive functioning in early psychosis specific associations of tnf α and il 6 with social cognition |
| topic | clinical high risk IL-6 psychosis schizophrenia TNF-α |
| url | https://www.cambridge.org/core/product/identifier/S0924933825100631/type/journal_article |
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