CELL-FREE DNA AND INFLAMMATORY CYTOKINES: NOVEL BIOMARKER SIGNATURE IN BIPOLAR DISORDER

Circulating cell-free DNA (ccfDNA) concentrations in biological fluids are elevated during pathological conditions, reflecting increased cellular stress, tissue injury, and disease-specific pathophysiological mechanisms. Recent evidence suggests ccfDNA holds promise as a diagnostic and prognostic biomarker in psychiatric disorders, including schizophrenia, major depression, and bipolar disorder. Furthermore, ccfDNA has emerged as a potential indicator of inflammatory states. While inflammatory cytokines are established biomarkers in psychiatric illness, the underlying molecular mechanisms linking ccfDNA and inflammation remain poorly characterized.This study investigated the relationship between plasma ccfDNA levels and inflammatory cytokine expression in bipolar disorder, and to evaluate the potential utility of ccfDNA as a diagnostic biomarker. We compared patients with bipolar disorder to healthy controls who were matched for age and sex. Plasma ccfDNA concentrations and inflammatory cytokine gene expression were quantified using qPCR. DNA methylation of transposable elements (TEs) was assessed by pyrosequencing. Patients with bipolar disorder exhibited significant alterations in both plasma ccfDNA levels and inflammatory cytokine gene expression compared to controls. Correlation analyses demonstrated a strong positive association between ccfDNA concentrations and inflammatory cytokine expression profiles. Additionally, we identified specific alterations in TEs methylation patterns correlated with these inflammatory changes. This study provides novel evidence supporting ccfDNA as a promising plasma-based biomarker for bipolar disorder. Our findings reveal specific ccfDNA expression signatures that correlate with inflammatory cytokine dysregulation, suggesting a mechanistic link between cell-free DNA and neuroinflammatory processes in bipolar disorder. These results warrant further investigation into the clinical utility of ccfDNA for diagnosis and monitoring of psychiatric disorders.