Oxidative stress in schizophrenia and bipolar disorders, results from a 2-year follow-up study of two prospective...

Enhanced oxidative stress generated nucleoside damage seems to contribute to accelerated aging in patients with severe mental illness and may be most pronounced in patients with schizophrenia but also in patients with bipolar disorder compared with healthy controls.

To investigate whether oxidative stress markers differ between patients with schizophrenia (SCZ), bipolar disorder (BD), and healthy control individuals (HC) followed for two years we compared levels of oxidative stress generated damage to DNA (8-oxodG) and RNA (8-oxoGuo) in 403 patients with schizophrenia and overweight (847 visits), 358 patients newly diagnosed with BD (627 visits), and 198 healthy control individuals (359 visits) while adjusting for sex, age and BMI as potential confounders.

RNA damage levels were 1.27-fold higher (95 %CI = 1.20-1.33, p_adjusted < 0.001) in patients with SCZ compared with HC at baseline and 1.16-fold higher (95 %CI = 1.11-1.22, p_adjusted < 0.001) in patients with BD compared with HC, and the differences persisted over time. RNA damage levels were also persistently higher in SCZ compared with BD with a 1.09-fold-difference (95 %CI = 1.04-1.14, p_adjusted < 0.001) at baseline. DNA damage was most pronounced in patients with BD who had a 1.22-fold higher level at baseline (95 %CI = 1.15-1.30, p_adjusted < 0.001) compared to HC, and a 1.08-fold higher level (95 %CI = 1.02-1.14, p_adjusted = 0.013) compared with SCZ, while patients with SCZ had a 1.12-fold higher level (95 %CI 1.05-1.21, p_adjusted = 0.002) compared with HC. However, the differences attenuated over time and were no longer statistically significant after 2 years.

Overall, we found persistently increased RNA damage over time in patients with severe mental illness compared with HC, most pronounced in SCZ but also present in BD, supporting oxidative stress generated nucleoside damage as a potential driver of accelerated aging.