EXAMINATION OF BIOMARKERS INDICATING BLOOD-BRAIN BARRIER AND INTESTINAL BARRIER PERMEABILITY IN ADOLESCENTS WITH MAJOR DEPRESSIVE DISORDER
Project no. 32490 · Status: Kapanmış (Yayın bekleniyor) · 2024
Summary
<p>Introduction: Major Depressive Disorder (MDD) is a multifactorial mental disorder with markedly increasing prevalence and clinical severity during adolescence. Current psychoneuroimmunology literature suggests that disruption of intestinal barrier integrity, systemic inflammation, and blood-brain barrier (BBB) dysfunction play a central role in the pathophysiology of MDD. However, studies simultaneously examining comprehensive biochemical indicators of the gut-liver-brain axis in adolescent MDD samples remain extremely limited. Objective: This study aimed to compare serum levels of Zonulin, reflecting intestinal barrier permeability; FABP1, indicating hepatic and intestinal cellular damage; and Claudin-5, a biomarker of BBB integrity, between adolescents with MDD and healthy controls, and to investigate the associations of these biomarkers with clinical scale scores and sociodemographic variables. Methods: The study included 52 adolescents aged 12–18 years, diagnosed with MDD confirmed by the K-SADS-PL-DSM-5-T, medication-free for at least one month, who presented to the Department of Child and Adolescent Psychiatry at Ege University Faculty of Medicine between January 2025 and January 2026, along with 43 healthy controls matched for age, sex, and BMI. Serum Zonulin, FABP1, and Claudin-5 levels were measured by sandwich ELISA. Participants were assessed using the Beck Depression Inventory, DSM-5 Level 2 Depression, Anxiety, Sleep Disturbance, Somatic Symptoms, and Irritability Scales. Between-group comparisons were performed using independent samples t-test, correlation analyses using Pearson and Spearman methods, and diagnostic discrimination using ROC analysis. xv Results: Serum Zonulin levels in adolescents with MDD (249.22±227.04 ng/mL) were significantly higher compared to healthy controls (112.30±188.67 ng/mL) (p=0.002). No significant difference was found between groups in serum FABP1 and Claudin-5 levels (p>0.05). Across the total sample, Zonulin levels demonstrated significant positive correlations with depression severity, anxiety, sleep disturbance, somatic symptoms, and irritability scores (p<0.05). A strong correlation was detected between BMI and Zonulin in the patient group (r=0.692; p<0.01). Subgroup analyses revealed significantly elevated Zonulin levels in adolescents with a family history of suicide (p=0.006), while both Zonulin and Claudin-5 levels were concurrently elevated in adolescents whose fathers had a history of physical illness. ROC analysis demonstrated that Zonulin (AUC=0.760; cut-off: 76.1 ng/mL; sensitivity: 69.2%; specificity: 69.8%) and sleep score (AUC=0.797; cut-off: 18.5; sensitivity: 73.1%; specificity: 72.1%) could significantly discriminate MDD patients from healthy controls. Conclusion: This study supports that functional intestinal leakage — Zonulinmediated paracellular permeability increase — plays a central and triggering role in adolescent MDD, and explains the stable levels of FABP1 and Claudin-5 through the early-stage barrier dysfunction model. The findings provide important evidence supporting the view that adolescent MDD should be considered not merely as a mood disorder, but as a comprehensive disease process characterized by multisystemic neuroimmune barrier dysfunction along the gutliver-brain axis. </p>