Inflammatory and oxidative stress biomarkers in children and adolescents with bipolar disorder - A systematic review and meta-analysis.

Evidence suggests a role for low-grade inflammation and oxidative stress in the pathophysiology of bipolar disorder. We conducted a systematic review and meta-analysis of peripheral markers of inflammation and oxidative stress in children and adolescents under 20 years of age with bipolar disorder. We searched PubMed, Embase and psycINFO and performed random effects meta-analysis calculating standardized mean differences (SMD) of marker levels between patients with bipolar disorder and healthy control individuals. Ten studies comprising a total of 418 patients with bipolar disorder and 3017 healthy control individuals were included. The levels of C-Reactive Protein were higher in patients with bipolar disorder compared with healthy individuals (SMD 0.53; 95 %CI: 0.33-0.74; I2 = 0 %). For other biomarkers there were no statistically significant differences between groups. Findings were limited by a low number of studies and participants and methodological issues in the included studies. More and larger studies using rigorous methodology are needed to establish the role of inflammation and oxidative stress in children and adolescents with bipolar disorder.

Oxidation of DNA and RNA in young patients with newly diagnosed bipolar disorder and relatives.

Excessive oxidative stress-generated nucleoside damage seems to play a key role in bipolar disorder (BD) and may present a trait phenomenon associated with familial risk and is one of the putative mechanisms explaining accelerated atherosclerosis and premature cardiovascular diseases (CVD) in younger patients with BD. However, oxidative stress-generated nucleoside damage has not been studied in young BD patients and their unaffected relatives (UR). Therefore, we compared oxidative stress-generated damage to DNA and RNA in young patients newly diagnosed with BD, UR, and healthy control individuals (HC). Systemic oxidative stress-generated DNA and RNA damage levels were compared by analyzing urinary levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine and 8-oxo-7,8-dihydroguanosine in participants aged 15-25 years, including 133 patients newly diagnosed with BD, 57 UR, and 83 HC. Compared with HC, damage to DNA was 21.8% higher in BD patients (B = 1.218, 95% CI = 1.111-1.335, p = <0.001) and 22.5% higher in UR (B = 1.225, 95% CI = 1.090-1.377, p = <0.002), while damage to RNA was 14.8% higher in BD patients (B = 1.148, 95% CI = 1.082-1.219, p = <0.001) and 14.0% higher in UR (B = 1.140, 95% CI = 1.055-1.230, p = < 0.001) in models adjusted for sex and age after correction for multiple comparison. Levels did not differ between patients with BD and UR. Our findings support higher oxidative stress-generated nucleoside damage being a trait phenomenon in BD associated with familial risk and highlight the importance of early diagnosis and treatment to prevent illness progression and development of premature CVD.