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Oxidative stress markers in bipolar disorder and first-degree relatives: differential associations of ischemia-modified albumin and superoxide dismutase
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DOI：10.3389/fpsyt.2026.1885863.png)
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Abstract
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BackgroundOxidative stress has been implicated in the pathophysiology of bipolar disorder (BD); potentially contributing to neuroprogression and cellular dysfunction. However; whether specific oxidative stress markers reflect disease expression or familial vulnerability remains unclear. This study aimed to evaluate thiol-disulfide homeostasis (TDH); ischemia-modified albumin (IMA); ferroxidase; and superoxide dismutase (SOD) levels in patients with BD; their unaffected first-degree relatives (FDRs); and healthy controls (HCs).MethodsIn this cross-sectional study; 50 patients with BD; 40 unaffected FDRs; and 50 HCs were included. Psychiatric diagnoses were confirmed using SCID-5; and remission was defined by Young Mania Rating Scale and Hamilton Depression Rating Scale scores <7. Fasting blood samples were analyzed for TDH parameters; IMA; ferroxidase; and SOD. Group differences were assessed using appropriate statistical tests; and multivariable linear regression analyses were performed; adjusting for age; sex; smoking status; and body mass index. Additional models further adjusted for medication use. Receiver operating characteristic (ROC) analyses were conducted to evaluate discriminative performance.ResultsIMA levels were significantly higher in BD patients than in HCs and remained significant after adjustment for potential confounders (β = 0.17; p = 0.007). No significant difference in IMA levels was observed between FDRs and HCs. SOD levels were significantly elevated in both BD (β = 0.37; p = 0.015) and FDR groups (β = 0.41; p = 0.009) compared with HCs. After additional adjustment for medication use; the difference remained significant only in FDRs. Initial differences in thiol parameters between BD and FDR groups were no longer significant after adjustment; with age emerging as a major determinant. Ferroxidase levels did not differ significantly between groups. ROC analyses demonstrated modest discriminative performance for IMA and SOD (AUC range: 0.63–0.66).ConclusionsElevated IMA levels in BD may reflect disease-related oxidative stress; whereas increased SOD levels observed in both BD patients and unaffected FDRs raise the possibility that SOD may be associated with familial vulnerability. However; the modest discriminative performance of these biomarkers and the cross-sectional design warrant cautious interpretation. Longitudinal studies are needed to clarify their potential role as biomarkers of disease-related oxidative stress and familial risk in BD.
Keywords:
oxidative stress
bipolar disorder
first-degree relatives
thiol
superoxide dismutase
ischemia-modified albumin
disulfides
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