Depressive and Negative Symptoms in the Early and Established Stages of Schizophrenia: Integrating Structural Brain Alterations, Cognitive Performance, and Plasma Interleukin 6 Levels
Background: Depressive and negative symptoms are related to poor functional outcomes in schizophrenia. Cognitive deficits, reduced brain cortical thickness and volumes, and inflammation may contribute to depressive and negative symptoms, but pharmacological treatment and disease progression may conf...
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Elsevier
2025-03-01
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| Series: | Biological Psychiatry Global Open Science |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667174324001423 |
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| author | Fabiana Corsi-Zuelli Gary Donohoe Siân Lowri Griffiths Cristina M. Del-Ben Andrew J. Watson Tom Burke Paris A. Lalousis Declan McKernan Derek Morris John Kelly Colm McDonald Saahithh R. Patlola Carmine Pariante Nicholas M. Barnes Golam M. Khandaker John Suckling Bill Deakin Rachel Upthegrove Maria R. Dauvermann |
| author_facet | Fabiana Corsi-Zuelli Gary Donohoe Siân Lowri Griffiths Cristina M. Del-Ben Andrew J. Watson Tom Burke Paris A. Lalousis Declan McKernan Derek Morris John Kelly Colm McDonald Saahithh R. Patlola Carmine Pariante Nicholas M. Barnes Golam M. Khandaker John Suckling Bill Deakin Rachel Upthegrove Maria R. Dauvermann |
| author_sort | Fabiana Corsi-Zuelli |
| collection | DOAJ |
| description | Background: Depressive and negative symptoms are related to poor functional outcomes in schizophrenia. Cognitive deficits, reduced brain cortical thickness and volumes, and inflammation may contribute to depressive and negative symptoms, but pharmacological treatment and disease progression may confound the associations. Methods: We evaluated whether higher plasma interleukin 6 (IL-6) levels would be associated with more severe negative or depressive symptoms in schizophrenia and explored illness stage utilizing early (BeneMin [Benefit of Minocycline on Negative Symptoms of Psychosis: Extent and Mechanism], n = 201, 72.8% male) and established (iRELATE [Immune Response & Social Cognition in Schizophrenia], n = 94, 67.3% male) schizophrenia cohorts. Using structural equation modeling in a subsample (iRELATE: n = 42, 69.0% male; BeneMin: n = 102, 76.5% male) with data on structural brain metrics (cortical thickness and volume), general cognitive performance, and plasma IL-6 levels, we assessed the interrelationships between these variables on depressive and negative symptom severity in early and established schizophrenia samples combined and in early schizophrenia only. All analyses were adjusted for sex, age, and chlorpromazine equivalent dose. Results: Higher plasma IL-6 levels were related to more severe depressive symptoms in early schizophrenia (p < .05) and negative symptoms in established schizophrenia (p < .05). Structural equation modeling findings in early and established schizophrenia samples combined and early schizophrenia only showed that the interrelationship between higher plasma IL-6 levels, structural brain metrics, and general cognitive performance did not predict the severity of depressive and negative symptoms (p > .05). Higher plasma IL-6 levels and lower general cognitive performance were associated with reduced brain metrics (p < .05). Conclusions: Our results indicate that higher plasma IL-6 levels may be differently associated with the severity of depressive and negative symptoms dependent on the illness stage. Future work identifying elevated levels of inflammation in larger samples may allow stratification and personalized intervention by subgroups who are at risk of poor outcomes. |
| format | Article |
| id | doaj-art-08973707992240cfb17a64af79d1f2d7 |
| institution | Kabale University |
| issn | 2667-1743 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biological Psychiatry Global Open Science |
| spelling | doaj-art-08973707992240cfb17a64af79d1f2d72025-01-24T04:45:53ZengElsevierBiological Psychiatry Global Open Science2667-17432025-03-0152100429Depressive and Negative Symptoms in the Early and Established Stages of Schizophrenia: Integrating Structural Brain Alterations, Cognitive Performance, and Plasma Interleukin 6 LevelsFabiana Corsi-Zuelli0Gary Donohoe1Siân Lowri Griffiths2Cristina M. Del-Ben3Andrew J. Watson4Tom Burke5Paris A. Lalousis6Declan McKernan7Derek Morris8John Kelly9Colm McDonald10Saahithh R. Patlola11Carmine Pariante12Nicholas M. Barnes13Golam M. Khandaker14John Suckling15Bill Deakin16Rachel Upthegrove17Maria R. Dauvermann18Institute for Mental Health, School of Psychology, University of Birmingham, Birmingham, United Kingdom; Department of Neurosciences and Behaviour, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil; Address correspondence to Fabiana Corsi-Zuelli, M.Sc., Ph.D.Centre for Neuroimaging, Cognition and Genomics, School of Psychology, University of Galway, Galway, IrelandInstitute for Mental Health, School of Psychology, University of Birmingham, Birmingham, United KingdomDepartment of Neurosciences and Behaviour, Ribeirão Preto Medical School, University of São Paulo, São Paulo, BrazilDepartment of Clinical and Motor Neuroscience, University College London, Queen Square Institute of Neurology, London, United KingdomCentre for Neuroimaging, Cognition and Genomics, School of Psychology, University of Galway, Galway, IrelandDepartment of Psychosis Studies, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, London, United KingdomPharmacology & Therapeutics, School of Medicine, University of Galway, Galway, IrelandCentre for Neuroimaging, Cognition and Genomics, School of Psychology, University of Galway, Galway, IrelandPharmacology & Therapeutics, School of Medicine, University of Galway, Galway, IrelandCentre for Neuroimaging, Cognition and Genomics, School of Psychology, University of Galway, Galway, IrelandPharmacology & Therapeutics, School of Medicine, University of Galway, Galway, IrelandDepartment of Psychological Medicine, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, London, United KingdomCollege of Medical and Dental Sciences, University of Birmingham, Birmingham, United KingdomMRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom; Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom; NIHR Bristol Biomedical Research Centre, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, United KingdomDepartment of Psychiatry, University of Cambridge, Cambridge, United Kingdom; Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, United KingdomDivision of Neuroscience and Experimental Psychology, Faculty of Biology, Medicine and Health, School of the Biological Sciences, University of Manchester, Manchester, United KingdomInstitute for Mental Health, School of Psychology, University of Birmingham, Birmingham, United Kingdom; Department of Psychiatry, University of Oxford, Oxford, United KingdomInstitute for Mental Health, School of Psychology, University of Birmingham, Birmingham, United Kingdom; Maria R. Dauvermann, Ph.D.Background: Depressive and negative symptoms are related to poor functional outcomes in schizophrenia. Cognitive deficits, reduced brain cortical thickness and volumes, and inflammation may contribute to depressive and negative symptoms, but pharmacological treatment and disease progression may confound the associations. Methods: We evaluated whether higher plasma interleukin 6 (IL-6) levels would be associated with more severe negative or depressive symptoms in schizophrenia and explored illness stage utilizing early (BeneMin [Benefit of Minocycline on Negative Symptoms of Psychosis: Extent and Mechanism], n = 201, 72.8% male) and established (iRELATE [Immune Response & Social Cognition in Schizophrenia], n = 94, 67.3% male) schizophrenia cohorts. Using structural equation modeling in a subsample (iRELATE: n = 42, 69.0% male; BeneMin: n = 102, 76.5% male) with data on structural brain metrics (cortical thickness and volume), general cognitive performance, and plasma IL-6 levels, we assessed the interrelationships between these variables on depressive and negative symptom severity in early and established schizophrenia samples combined and in early schizophrenia only. All analyses were adjusted for sex, age, and chlorpromazine equivalent dose. Results: Higher plasma IL-6 levels were related to more severe depressive symptoms in early schizophrenia (p < .05) and negative symptoms in established schizophrenia (p < .05). Structural equation modeling findings in early and established schizophrenia samples combined and early schizophrenia only showed that the interrelationship between higher plasma IL-6 levels, structural brain metrics, and general cognitive performance did not predict the severity of depressive and negative symptoms (p > .05). Higher plasma IL-6 levels and lower general cognitive performance were associated with reduced brain metrics (p < .05). Conclusions: Our results indicate that higher plasma IL-6 levels may be differently associated with the severity of depressive and negative symptoms dependent on the illness stage. Future work identifying elevated levels of inflammation in larger samples may allow stratification and personalized intervention by subgroups who are at risk of poor outcomes.http://www.sciencedirect.com/science/article/pii/S2667174324001423Depressive and negative symptomsGeneral cognitive functionPlasma interleukin 6SchizophreniaStructural equation modelingStructural MRI |
| spellingShingle | Fabiana Corsi-Zuelli Gary Donohoe Siân Lowri Griffiths Cristina M. Del-Ben Andrew J. Watson Tom Burke Paris A. Lalousis Declan McKernan Derek Morris John Kelly Colm McDonald Saahithh R. Patlola Carmine Pariante Nicholas M. Barnes Golam M. Khandaker John Suckling Bill Deakin Rachel Upthegrove Maria R. Dauvermann Depressive and Negative Symptoms in the Early and Established Stages of Schizophrenia: Integrating Structural Brain Alterations, Cognitive Performance, and Plasma Interleukin 6 Levels Biological Psychiatry Global Open Science Depressive and negative symptoms General cognitive function Plasma interleukin 6 Schizophrenia Structural equation modeling Structural MRI |
| title | Depressive and Negative Symptoms in the Early and Established Stages of Schizophrenia: Integrating Structural Brain Alterations, Cognitive Performance, and Plasma Interleukin 6 Levels |
| title_full | Depressive and Negative Symptoms in the Early and Established Stages of Schizophrenia: Integrating Structural Brain Alterations, Cognitive Performance, and Plasma Interleukin 6 Levels |
| title_fullStr | Depressive and Negative Symptoms in the Early and Established Stages of Schizophrenia: Integrating Structural Brain Alterations, Cognitive Performance, and Plasma Interleukin 6 Levels |
| title_full_unstemmed | Depressive and Negative Symptoms in the Early and Established Stages of Schizophrenia: Integrating Structural Brain Alterations, Cognitive Performance, and Plasma Interleukin 6 Levels |
| title_short | Depressive and Negative Symptoms in the Early and Established Stages of Schizophrenia: Integrating Structural Brain Alterations, Cognitive Performance, and Plasma Interleukin 6 Levels |
| title_sort | depressive and negative symptoms in the early and established stages of schizophrenia integrating structural brain alterations cognitive performance and plasma interleukin 6 levels |
| topic | Depressive and negative symptoms General cognitive function Plasma interleukin 6 Schizophrenia Structural equation modeling Structural MRI |
| url | http://www.sciencedirect.com/science/article/pii/S2667174324001423 |
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