Immune-Inflammatory Biomarkers Predict Cognition and Social Functioning in Patients With Type 2 Diabetes Mellitus, Major Depressive Disorder, Bipolar Disorder, and Schizophrenia: A 1-Year Follow-Up Study

Marta Garés-Caballer; Joan Vicent Sánchez-Ortí; Patricia Correa-Ghisays; Vicent Balanzá-Martínez; Gabriel Selva-Vera; Joan Vila-Francés; Rafael Magdalena-Benedito; Constanza San-Martin; Victor M Victor; Irene Escribano-Lopez; Antonio Hernandez-Mijares; Juliana Vivas-Lalinde; Eduard Vieta; Juan C Leza; Rafael Tabarés-Seisdedos

doi:10.3389/fneur.2022.883927

Immune-Inflammatory Biomarkers Predict Cognition and Social Functioning in Patients With Type 2 Diabetes Mellitus, Major Depressive Disorder, Bipolar Disorder, and Schizophrenia: A 1-Year Follow-Up Study

Front Neurol. 2022 Jun 2:13:883927. doi: 10.3389/fneur.2022.883927. eCollection 2022.

Authors

Marta Garés-Caballer¹, Joan Vicent Sánchez-Ortí^{2

3

4}, Patricia Correa-Ghisays^{2

3

4

5}, Vicent Balanzá-Martínez^{1

2

3

5

6}, Gabriel Selva-Vera^{1

2

3

5}, Joan Vila-Francés⁷, Rafael Magdalena-Benedito⁷, Constanza San-Martin^{2

3

8}, Victor M Victor^{9

10

11}, Irene Escribano-Lopez⁹, Antonio Hernandez-Mijares⁹, Juliana Vivas-Lalinde¹², Eduard Vieta^{5

13}, Juan C Leza^{5

14}, Rafael Tabarés-Seisdedos^{1

2

3

5}

Affiliations

¹ Teaching Unit of Psychiatry and Psychological Medicine, Department of Medicine, University of Valencia, Valencia, Spain.
² INCLIVA-Health Research Institute, Valencia, Spain.
³ TMAP-Evaluation Unit of Personal Autonomy, Dependency and Serious Mental Disorders, University of Valencia, Valencia, Spain.
⁴ Faculty of Psychology and Speech Therapy, University of Valencia, Valencia, Spain.
⁵ Center for Biomedical Research in Mental Health Network (CIBERSAM), Institute of Health Carlos III, Madrid, Spain.
⁶ Mental Health Unit of Catarroja, Valencia, Spain.
⁷ IDAL-Intelligent Data Analysis Laboratory, University of Valencia, Valencia, Spain.
⁸ Department of Physiotherapy, University of Valencia, Valencia, Spain.
⁹ Service of Endocrinology and Nutrition, University Hospital Dr. Peset, Valencia, Spain.
¹⁰ Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain.
¹¹ Department of Physiology, University of Valencia, Valencia, Spain.
¹² Departament of Psychiatry, Mental Health Service of Manises, Valencia, Spain.
¹³ Barcelona Bipolar and Depressive Disorders Unit, Institute of Neurosciences, Hospital Clínic of Barcelona, University of Barcelona, IDIBAPS, Catalonia, Spain.
¹⁴ Department of Pharmacology and Toxicology, Faculty of Medicine, Complutense University of Madrid, Madrid, Spain.

Abstract

Background: Systemic, low-grade immune-inflammatory activity, together with social and neurocognitive performance deficits are a transdiagnostic trait of people suffering from type 2 diabetes mellitus (T2DM) and severe mental illnesses (SMIs), such as schizophrenia (SZ), major depressive disorder (MDD), and bipolar disorder (BD). We aimed to determine if immune-inflammatory mediators were significantly altered in people with SMIs or T2DM compared with healthy controls (HC) and whether these biomarkers could help predict their cognition and social functioning 1 year after assessment.

Methods: We performed a prospective, 1-year follow-up cohort study with 165 participants at baseline (TB), including 30 with SZ, 42 with BD, 35 with MDD, 30 with T2DM, and 28 HC; and 125 at 1-year follow-up (TY), and determined executive domain (ED), global social functioning score (GSFS), and peripheral blood immune-inflammatory and oxidative stress biomarkers.

Results: Participants with SMIs and T2DM showed increased peripheral levels of inflammatory markers, such as interleukin-10 (p < 0.01; η² p = 0.07) and tumor necrosis factor-α (p < 0.05; η² p = 0.08); and oxidative stress biomarkers, such as reactive oxygen species (ROS) (p < 0.05; η² p = 0.07) and mitochondrial ROS (p < 0.01; η² p = 0.08). The different combinations of the exposed biomarkers anticipated 46-57.3% of the total ED and 23.8-35.7% of GSFS for the participants with SMIs.

Limitations: Participants' treatment, as usual, was continued without no specific interventions; thus, it was difficult to anticipate substantial changes related to the psychopharmacological pattern.

Conclusion: People with SMIs show significantly increased levels of peripheral immune-inflammatory biomarkers, which may contribute to the neurocognitive and social deficits observed in SMIs, T2DM, and other diseases with systemic immune-inflammatory activation of chronic development. These parameters could help identify the subset of patients who could benefit from immune-inflammatory modulator strategies to ameliorate their functional outcomes.

Keywords: bipolar disorder; diabetes mellitus; executive function; immune–inflammation; major depressive disorder; schizophrenia; social functioning; transdiagnostic analysis.

Copyright © 2022 Garés-Caballer, Sánchez-Ortí, Correa-Ghisays, Balanzá-Martínez, Selva-Vera, Vila-Francés, Magdalena-Benedito, San-Martin, Victor, Escribano-Lopez, Hernandez-Mijares, Vivas-Lalinde, Vieta, Leza and Tabarés-Seisdedos.