Diagnostic Potential of Vitamin D, Chromogranin A, Tumor Necrosis Factor-α, and Cortisol Levels in Attention-Deficit/Hyperactivity Disorder: A Meta-Analysis

Background: Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neuro-developmental disorder that is linked to attention, hyperactivity, and impulse control. There is emerging evidence that markers like Vitamin D, Chromogranin A (CgA), Tumor Necrosis Factor-α (TNF-α), and cortisol can be used to explain its biological mechanisms. Objective: To quantify serum levels of Vitamin D, CgA, TNF-α, and cortisol in ADHD patients and control subjects, and establish their diagnostic value. Methods: According to PRISMA guidelines, we searched Google Scholar and PubMed systematically for observational studies that assess the serum levels of the selected biomarkers in ADHD and control groups. The studies that passed the inclusion criteria were screened, extracted, and analyzed using a random-effects model. The effect sizes were presented as Hedges' g. Heterogeneity was assessed using I² statistics, and potential publication bias was assessed using funnel plots and Egger's test. Meta-regression was conducted to explore moderators like age, gender, and comorbidities. Results: 28 studies were included. Vitamin D was significantly lower in ADHD patients compared to controls (SMD = -1.19, 95% CI: -2.04 to -0.33, p = 0.0068), but heterogeneity was high (I² = 96.5%). TNF-α was significantly lower (SMD = -0.39, 95% CI: -0.65 to -0.13, p = 0.0033) with low heterogeneity (I² = 22.0%). Cortisol was significantly lower (SMD = -0.78, 95% CI: -1.48 to -0.08, p = 0.0280), with high heterogeneity (I² = 94.3%). Chromogranin A results were inconclusive due to limited data. Meta-regression revealed that age, male sex, and comorbidities significantly moderated Vitamin D effect sizes, but other predictors were not significant. Conclusion: Vitamin D, TNF-α, and cortisol are all greatly diminished in ADHD and are potential addition-al diagnostic markers. CgA is worthy of further study.