Bipolar disorder and somatic diseases: Focus on oxidative stress markers

Bipolar disorder (BD) is associated with a substantial burden of somatic diseases, including cardiovascular, neurodegenerative, and inflammatory conditions. However, the biological continuity linking the core pathophysiology of BD to these somatic manifestations remains poorly understood. Oxidative stress is increasingly recognized as a shared biological process across many medical conditions that commonly co-occur with BD and has been extensively investigated using diverse biomarkers, consistently demonstrating redox imbalance across illness stages and mood states. This evidence supports oxidative stress as a core biological process contributing to multisystem vulnerability rather than merely a secondary consequence of affective episodes. This review employed a narrative synthesis approach. Somatic diseases most frequently observed in BD were identified through systematic reviews and meta-analyses, and oxidative stress-related biomarkers associated with BD were examined alongside their alterations in commonly comorbid somatic diseases. Evidence from epidemiological syntheses, biomarker studies, and mechanistic research was integrated to identify converging findings, inconsistencies, and key research gaps. Across systematic syntheses, thirteen major non-communicable somatic disease categories were consistently associated with BD, particularly cardiometabolic, cardiovascular, endocrine, inflammatory, and neurodegenerative conditions. In parallel, BD research demonstrates alterations across multiple oxidative stress domains, with the most consistent findings observed for lipid peroxidation markers (e.g., TBARS, MDA) and oxidative nucleic acid damage (e.g., 8-oxo-dG, 8-OHGuo), whereas evidence for protein oxidation and antioxidant enzyme activity is more heterogeneous and state dependent. Notably, no studies directly examine associations between oxidative stress markers and objectively measured somatic comorbidity or multimorbidity in BD, and current evidence therefore relies on indirect triangulation between robust redox alterations in BD and oxidative stress mechanisms established in general medical populations. Overall, oxidative stress appears to represent a systemic biological feature of BD that aligns mechanistically with the somatic diseases contributing to its mortality gap. However, biomarker heterogeneity, predominantly cross-sectional study designs, and the lack of integrated somatic phenotyping limit clinical interpretation. Longitudinal, state-sensitive studies linking redox dysregulation with somatic outcomes are needed to determine whether oxidative stress reflects cumulative systemic vulnerability rather than episodic illness activity.