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

Abstract

BackgroundSystemic, 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.MethodsWe 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.ResultsParticipants with SMIs and T2DM showed increased peripheral levels of inflammatory markers, such as interleukin-10 (p < 0.01; η2p = 0.07) and tumor necrosis factor-α (p < 0.05; η2p = 0.08); and oxidative stress biomarkers, such as reactive oxygen species (ROS) (p < 0.05; η2p = 0.07) and mitochondrial ROS (p < 0.01; η2p = 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.LimitationsParticipants' treatment, as usual, was continued without no specific interventions; thus, it was difficult to anticipate substantial changes related to the psychopharmacological pattern.ConclusionPeople 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.

Plasma IGFBP-3 and IGFBP-5 levels are decreased during acute manic episodes in bipolar disorder patients

“…BD manic patients showed significantly higher TNF-α levels than controls at admission ( Kim et al, 2007 ; Junior et al, 2023 ; Polat et al, 2023 ), without receiving pharmacotherapy 2 ( Pandey et al, 2015 ) or 3 weeks before protein measurement ( Ortiz-Domínguez et al, 2007 ), when following stable treatment ( O'Brien et al, 2006 ; Kim et al, 2007 ; Kapczinski et al, 2011 ; Luo et al, 2016 ; Wang et al, 2016 ; Hoseth et al, 2017 ; Koga et al, 2019 ; Bavaresco et al, 2020 ; Zazula et al, 2022 ; Lu et al, 2023 ; Gong et al, 2022 ), and in both early ( Skibinska et al, 2022 ) and late BD stages ( Kauer-Sant Anna et al, 2009 ; Tatay-Manteiga et al, 2017 ), or significantly reduced levels in euthymic late patients but not in early BD patients ( Panizzutti et al, 2015 ). In other cases, no difference was found between controls and BD patients who were under medication ( Barbosa et al, 2011 ; Palacio et al, 2016 ; Doğanavşargil Baysal et al, 2019 ; Garés-Caballer et al, 2022 ; Jiang et al, 2022 ) with valproic acid monotherapy ( Chou et al, 2016 ) or at baseline when specified that BD patients had a manic episode ( Li et al, 2015 ; Jacoby et al, 2016 ) or were in their first episode ( Chen MH et al, 2020 ). During euthymia, TNF-α has also been unaltered compared to controls ( Kunz et al, 2011 ; Barbosa et al, 2012a ; Doganavsargil-Baysal et al, 2013 ; Wieck et al, 2014 ; Jacoby et al, 2016 ; Doğanavşargil Baysal et al, 2019 ; Millett et al, 2020 ; Vares et al, 2020 ).…”

Connecting Neurobiological Features with Interregional Dysconnectivity in Social-Cognitive Impairments of Schizophrenia

“…Therefore, a contribution of immune dysregulation to social-cognitive impairments in SZ patients is to be expected. Indeed, higher plasma levels of inflammatory components such as interleukin 10 (IL-10) predict social-functioning impairments [139]. Another study even found that higher IL-10 levels lead to misinterpretation of social cues and that elevated IL-2 correlates with other social-cognitive measures in SZ patients [140,141].…”