Inflammatory and Neurodegenerative Biomarkers in Bipolar I Disorder: A Cross-Sectional Study

Objective: Bipolar disorder (BD) is increasingly recognized as a systemic illness involving chronic inflammation, glial dysfunction, and neuronal dysregulation in addition to mood instability. Recent studieshave suggested that biomarkers such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-1 receptor antagonist (IL-1RA), S100B, and neuron-specific enolase (NSE) may reflect underlying pathophysiological processes in BD. However, findings remain inconsistent, particularly across mood states. Thisstudy aimed to investigate serum levels of IL-6, TNF-α, IL-1RA, S100B, and NSE in patients with bipolar Idisorder (BD-I) across euthymic, manic, and depressive phases, and to compare them with healthy controls. Additionally, correlations between biomarker levels and clinical symptom severity were examined.Methods: Serum levels were measured in 77 patients with BD-I (50 euthymic, 20 manic, and 7 depressed)and 50 healthy controls. Correlations were assessed between these levels and the Young Mania RatingScale (YMRS), the Montgomery–Åsberg Depression Rating Scale, the Clinical Global Impressions-SeverityScale (CGI-S), and the Positive and Negative Syndrome Scale (PANSS)–positive symptoms subscale, as wellas other clinical variables.Results: Indicating a trait-like inflammatory profile, IL-6 levels were considerably higher in the BD groupand had a positive correlation with YMRS, PANSS, and CGI scores. Conversely, levels of IL-1RA, TNF-α, S100B,and NSE were markedly decreased in patients. NSE levels exhibited an inverse connection with clinicalseverity, potentially signifying neuroprogressive alterations.Conclusion: The findings support the role of IL-6 as a state-independent inflammatory marker in BD, whilereductions in NSE may reflect chronic neurobiological dysregulation. These findings may have implications for biomarker-guided monitoring or treatment stratification in BD. Further research is warranted todetermine whether these biomarkers can serve as reliable indicators of disease progression, treatmentresponse, and mood state in clinical settings.Cite this article as: Taşdemir İ, Çakır S. Inflammatory and neurodegenerative biomarkers in bipolar I disorder: a crosssectional study. Neuropsychiatr Invest. 63, 0044, doi:10.5152/NeuropsychiatricInvest.2025.25044.