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

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.

Figure 1

Shared immune-inflammatory biomarkers that predict neurocognitive functioning in clinical groups. T2DM, type 2 diabetes mellitus; MDD, major depressive disorder; BD, bipolar disorder; SZ, schizophrenia; GSH, glutathione; HGB, hemoglobin; HCT, hematocrit; CRP, C-reactive protein; WBC, white blood cells; N, neutrophils; AN, absolute neutrophils; AL, absolute lymphocytes; M, monocytes; AM, absolute monocytes; mROS, mitochondrial reactive oxygen species; SOD, superoxide dismutase.

Figure 2

Amount of GSFS variance explained by immune-inflammatory biomarkers across clinical groups. GSFS, Global Social Functioning Score; T2DM, type 2 diabetes mellitus; MDD, major depressive disorder; BD, bipolar disorder; SZ, schizophrenia.

Figure 3

Variance explained by immune-inflammatory biomarkers in HC group. HC, healthy control; ED, Executive Domain; CF, cognitive flexibility; VF, verbal fluency; WM, working memory; PS, processing speed; GSFS, Global Social Functioning Score.