Specific immune-inflammatory profiles and neurocognitive deficits predict illness trajectories in people with type 2 diabetes mellitus or psychiatric disorders

Introduction: Psychiatric disorders and type 2 diabetes mellitus (T2DM) are chronic conditions that are often comorbid with each other. Neurocognitive and functional impairments are associated with numerous clinical changes during the course of illness. Immune-inflammatory dysfunction is emerging as...

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Main Authors: Joan Vicent Sánchez-Ortí, Patricia Correa-Ghisays, Vicent Balanzá-Martínez, Gabriel Selva-Vera, Víctor M. Victor, Constanza San Martin Valenzuela, Pau Soldevila-Matías, Fabián Robledo-Yagüe, María Flores-Rodero, Jon Sánchez-Valle, Jaume Forés-Martos, Diego Macías Saint-Gerons, Inmaculada Fuentes-Durá, Rafael Tabarés-Seisdedos
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Language:English
Published: Elsevier 2025-03-01
Series:Brain, Behavior, & Immunity - Health
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Online Access:http://www.sciencedirect.com/science/article/pii/S2666354625000201
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author Joan Vicent Sánchez-Ortí
Patricia Correa-Ghisays
Vicent Balanzá-Martínez
Gabriel Selva-Vera
Víctor M. Victor
Constanza San Martin Valenzuela
Pau Soldevila-Matías
Fabián Robledo-Yagüe
María Flores-Rodero
Jon Sánchez-Valle
Jaume Forés-Martos
Diego Macías Saint-Gerons
Inmaculada Fuentes-Durá
Rafael Tabarés-Seisdedos
author_facet Joan Vicent Sánchez-Ortí
Patricia Correa-Ghisays
Vicent Balanzá-Martínez
Gabriel Selva-Vera
Víctor M. Victor
Constanza San Martin Valenzuela
Pau Soldevila-Matías
Fabián Robledo-Yagüe
María Flores-Rodero
Jon Sánchez-Valle
Jaume Forés-Martos
Diego Macías Saint-Gerons
Inmaculada Fuentes-Durá
Rafael Tabarés-Seisdedos
author_sort Joan Vicent Sánchez-Ortí
collection DOAJ
description Introduction: Psychiatric disorders and type 2 diabetes mellitus (T2DM) are chronic conditions that are often comorbid with each other. Neurocognitive and functional impairments are associated with numerous clinical changes during the course of illness. Immune-inflammatory dysfunction is emerging as a critical factor in the progression of these disorders. This study aimed to identify neurocognitive deficits and immune-inflammatory biomarkers that are suitable for signaling different illness trajectories from transdiagnostic and longitudinal perspectives. Methods: Clinical status, neurocognitive and functional performance, and peripheral blood biomarkers of immune-inflammation were assessed twice a year in 165 individuals, including 30 with schizophrenia (SZ), 42 with bipolar disorder (BD), 35 with major depressive disorder (MDD), 30 with T2DM, and 28 healthy controls (HCs). Participants with chronic illness (n = 137) were stratified into quartiles, taking their years of illness duration at baseline as a reference into categories of short illness duration (SD; n = 37), middle illness duration (MD; n = 36), long illness duration (LD; n = 32), and very long illness duration (VLD; n = 32). The illness duration was used to measure the illness trajectory, and the exposure of interest was clinical progression, calculated as the difference between clinical severity at baseline (T1) and after 1 year (T2). Results: Neurocognitive impairment was more significant in the VLD group than in the other groups, with small–moderate effect sizes (F = 2.9 to 9.3; p < 0.05−0.0001; η2p = 0.06−0.24). Moreover, the HC group showed significantly higher functional outcomes than the other groups (F = 5.8 to 6.0; p < 0.0001; η2p = 0.13−0.16). On the contrary, the HC group showed lower levels of immune-inflammatory markers (white blood cell count, absolute neutrophils, absolute monocytes, absolute basophiles, neutrophils/lymphocyte ratio, and platelets/lymphocyte ratio [PLR]) (F = 2.9 to 6.7; p < 0.05−0.0001; η2p = 0.07−0.18). In all groups, significant prospective associations were observed between cognitive function (short-term memory and processing speed), global functional scores, immune-inflammatory biomarkers (monocyte/lymphocyte ratio [MLR] and PLR), and clinical status (p < 0.05). Furthermore, a similar combination of neurocognitive deficits and immune-inflammatory alterations compounded the transdiagnostic model that best discriminated the different illness trajectories (χ2 = 67.4 to 78.7; p < 0.05−0.01). Conclusions: Neurocognitive dysfunction and systemic inflammation are associated with prolonged illness trajectories in individuals with psychiatric disorders and T2DM. An immune-inflammatory profile and neurocognitive and functional performance may be valuable to differentiate individuals with different illness trajectories. These findings have potential translational utility for early transdiagnostic interventions targeting these groups.
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spelling doaj-art-e8e19bd4eaf5498998cc7c5bd1d2d51b2025-08-20T02:58:52ZengElsevierBrain, Behavior, & Immunity - Health2666-35462025-03-014410096210.1016/j.bbih.2025.100962Specific immune-inflammatory profiles and neurocognitive deficits predict illness trajectories in people with type 2 diabetes mellitus or psychiatric disordersJoan Vicent Sánchez-Ortí0Patricia Correa-Ghisays1Vicent Balanzá-Martínez2Gabriel Selva-Vera3Víctor M. Victor4Constanza San Martin Valenzuela5Pau Soldevila-Matías6Fabián Robledo-Yagüe7María Flores-Rodero8Jon Sánchez-Valle9Jaume Forés-Martos10Diego Macías Saint-Gerons11Inmaculada Fuentes-Durá12Rafael Tabarés-Seisdedos13INCLIVA - Health Research Institute, Valencia, Spain; TMAP - Evaluation Unit in Personal Autonomy, Dependency and Serious Mental Disorders, University of Valencia, Valencia, Spain; Center for Biomedical Research in Mental Health Network (CIBERSAM), Health Institute, Carlos III, Madrid, Spain; Faculty of Psychology, University of Valencia, Valencia, SpainINCLIVA - Health Research Institute, Valencia, Spain; TMAP - Evaluation Unit in Personal Autonomy, Dependency and Serious Mental Disorders, University of Valencia, Valencia, Spain; Center for Biomedical Research in Mental Health Network (CIBERSAM), Health Institute, Carlos III, Madrid, Spain; Faculty of Psychology, University of Valencia, Valencia, SpainINCLIVA - Health Research Institute, Valencia, Spain; TMAP - Evaluation Unit in Personal Autonomy, Dependency and Serious Mental Disorders, University of Valencia, Valencia, Spain; Center for Biomedical Research in Mental Health Network (CIBERSAM), Health Institute, Carlos III, Madrid, Spain; Teaching Unit of Psychiatry and Psychological Medicine, Department of Medicine, University of Valencia, Valencia, Spain; VALSME (VALencia Salut Mental i Estigma) Research Group, University of Valencia, Valencia, Spain; Corresponding author. Teaching Unit of Psychiatry and Psychological Medicine, Department of Medicine, University of Valencia, Blasco Ibáñez 15, 46010, Valencia. Spain.INCLIVA - Health Research Institute, Valencia, Spain; TMAP - Evaluation Unit in Personal Autonomy, Dependency and Serious Mental Disorders, University of Valencia, Valencia, Spain; Center for Biomedical Research in Mental Health Network (CIBERSAM), Health Institute, Carlos III, Madrid, Spain; Teaching Unit of Psychiatry and Psychological Medicine, Department of Medicine, University of Valencia, Valencia, SpainINCLIVA - Health Research Institute, Valencia, Spain; Department of Physiology, Faculty of Medicine and Dentistry, University of Valencia, Valencia, Spain; Service of Endocrinology and Nutrition, University Hospital Dr. Peset, Valencia, Spain; Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, SpainINCLIVA - Health Research Institute, Valencia, Spain; TMAP - Evaluation Unit in Personal Autonomy, Dependency and Serious Mental Disorders, University of Valencia, Valencia, Spain; Center for Biomedical Research in Mental Health Network (CIBERSAM), Health Institute, Carlos III, Madrid, Spain; Department of Physiotherapy, University of Valencia, Valencia, SpainINCLIVA - Health Research Institute, Valencia, Spain; TMAP - Evaluation Unit in Personal Autonomy, Dependency and Serious Mental Disorders, University of Valencia, Valencia, Spain; Department of Psychology, Faculty of Health Sciences, European University of Valencia, Valencia, SpainINCLIVA - Health Research Institute, Valencia, Spain; Teaching Unit of Psychiatry and Psychological Medicine, Department of Medicine, University of Valencia, Valencia, SpainTeaching Unit of Psychiatry and Psychological Medicine, Department of Medicine, University of Valencia, Valencia, Spain; Computational Biology Group, Life Sciences Department, Barcelona Supercomputing Center, Barcelona, SpainComputational Biology Group, Life Sciences Department, Barcelona Supercomputing Center, Barcelona, SpainINCLIVA - Health Research Institute, Valencia, Spain; TMAP - Evaluation Unit in Personal Autonomy, Dependency and Serious Mental Disorders, University of Valencia, Valencia, Spain; Center for Biomedical Research in Mental Health Network (CIBERSAM), Health Institute, Carlos III, Madrid, SpainINCLIVA - Health Research Institute, Valencia, Spain; Center for Biomedical Research in Mental Health Network (CIBERSAM), Health Institute, Carlos III, Madrid, Spain; Faculty of Nursery, University of Valladolid, Valladolid, SpainINCLIVA - Health Research Institute, Valencia, Spain; TMAP - Evaluation Unit in Personal Autonomy, Dependency and Serious Mental Disorders, University of Valencia, Valencia, Spain; Center for Biomedical Research in Mental Health Network (CIBERSAM), Health Institute, Carlos III, Madrid, Spain; Faculty of Psychology, University of Valencia, Valencia, SpainINCLIVA - Health Research Institute, Valencia, Spain; TMAP - Evaluation Unit in Personal Autonomy, Dependency and Serious Mental Disorders, University of Valencia, Valencia, Spain; Center for Biomedical Research in Mental Health Network (CIBERSAM), Health Institute, Carlos III, Madrid, Spain; Teaching Unit of Psychiatry and Psychological Medicine, Department of Medicine, University of Valencia, Valencia, Spain; Corresponding author. Teaching Unit of Psychiatry and Psychological Medicine, Department of Medicine, University of Valencia, Blasco Ibáñez 15, 46010, Valencia. Spain.Introduction: Psychiatric disorders and type 2 diabetes mellitus (T2DM) are chronic conditions that are often comorbid with each other. Neurocognitive and functional impairments are associated with numerous clinical changes during the course of illness. Immune-inflammatory dysfunction is emerging as a critical factor in the progression of these disorders. This study aimed to identify neurocognitive deficits and immune-inflammatory biomarkers that are suitable for signaling different illness trajectories from transdiagnostic and longitudinal perspectives. Methods: Clinical status, neurocognitive and functional performance, and peripheral blood biomarkers of immune-inflammation were assessed twice a year in 165 individuals, including 30 with schizophrenia (SZ), 42 with bipolar disorder (BD), 35 with major depressive disorder (MDD), 30 with T2DM, and 28 healthy controls (HCs). Participants with chronic illness (n = 137) were stratified into quartiles, taking their years of illness duration at baseline as a reference into categories of short illness duration (SD; n = 37), middle illness duration (MD; n = 36), long illness duration (LD; n = 32), and very long illness duration (VLD; n = 32). The illness duration was used to measure the illness trajectory, and the exposure of interest was clinical progression, calculated as the difference between clinical severity at baseline (T1) and after 1 year (T2). Results: Neurocognitive impairment was more significant in the VLD group than in the other groups, with small–moderate effect sizes (F = 2.9 to 9.3; p < 0.05−0.0001; η2p = 0.06−0.24). Moreover, the HC group showed significantly higher functional outcomes than the other groups (F = 5.8 to 6.0; p < 0.0001; η2p = 0.13−0.16). On the contrary, the HC group showed lower levels of immune-inflammatory markers (white blood cell count, absolute neutrophils, absolute monocytes, absolute basophiles, neutrophils/lymphocyte ratio, and platelets/lymphocyte ratio [PLR]) (F = 2.9 to 6.7; p < 0.05−0.0001; η2p = 0.07−0.18). In all groups, significant prospective associations were observed between cognitive function (short-term memory and processing speed), global functional scores, immune-inflammatory biomarkers (monocyte/lymphocyte ratio [MLR] and PLR), and clinical status (p < 0.05). Furthermore, a similar combination of neurocognitive deficits and immune-inflammatory alterations compounded the transdiagnostic model that best discriminated the different illness trajectories (χ2 = 67.4 to 78.7; p < 0.05−0.01). Conclusions: Neurocognitive dysfunction and systemic inflammation are associated with prolonged illness trajectories in individuals with psychiatric disorders and T2DM. An immune-inflammatory profile and neurocognitive and functional performance may be valuable to differentiate individuals with different illness trajectories. These findings have potential translational utility for early transdiagnostic interventions targeting these groups.http://www.sciencedirect.com/science/article/pii/S2666354625000201Illness trajectoriesNeurocognitionImmune-inflammationType 2 diabetes mellitusSchizophreniaBipolar disorder
spellingShingle Joan Vicent Sánchez-Ortí
Patricia Correa-Ghisays
Vicent Balanzá-Martínez
Gabriel Selva-Vera
Víctor M. Victor
Constanza San Martin Valenzuela
Pau Soldevila-Matías
Fabián Robledo-Yagüe
María Flores-Rodero
Jon Sánchez-Valle
Jaume Forés-Martos
Diego Macías Saint-Gerons
Inmaculada Fuentes-Durá
Rafael Tabarés-Seisdedos
Specific immune-inflammatory profiles and neurocognitive deficits predict illness trajectories in people with type 2 diabetes mellitus or psychiatric disorders
Brain, Behavior, & Immunity - Health
Illness trajectories
Neurocognition
Immune-inflammation
Type 2 diabetes mellitus
Schizophrenia
Bipolar disorder
title Specific immune-inflammatory profiles and neurocognitive deficits predict illness trajectories in people with type 2 diabetes mellitus or psychiatric disorders
title_full Specific immune-inflammatory profiles and neurocognitive deficits predict illness trajectories in people with type 2 diabetes mellitus or psychiatric disorders
title_fullStr Specific immune-inflammatory profiles and neurocognitive deficits predict illness trajectories in people with type 2 diabetes mellitus or psychiatric disorders
title_full_unstemmed Specific immune-inflammatory profiles and neurocognitive deficits predict illness trajectories in people with type 2 diabetes mellitus or psychiatric disorders
title_short Specific immune-inflammatory profiles and neurocognitive deficits predict illness trajectories in people with type 2 diabetes mellitus or psychiatric disorders
title_sort specific immune inflammatory profiles and neurocognitive deficits predict illness trajectories in people with type 2 diabetes mellitus or psychiatric disorders
topic Illness trajectories
Neurocognition
Immune-inflammation
Type 2 diabetes mellitus
Schizophrenia
Bipolar disorder
url http://www.sciencedirect.com/science/article/pii/S2666354625000201
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