Oxidative stress in early stage Bipolar Disorder and the association with response to lithium

Abstract

Background Several studies have described increased oxidative stress (OxS) parameters and imbalance of antioxidant enzymes in Bipolar Disorder (BD) but few is know about the impact of treatment at these targets. However, no study has evaluated OxS parameters in unmedicated early stage BD and their association with lithium treatment in bipolar depression. Methods Patients with BD I or II (n = 29) in a depressive episode were treated for 6 weeks with lithium. Plasma samples were collected at baseline and endpoint, and were also compared to age-matched controls (n = 28). The thiobarbituric acid reactive substances (TBARS), and the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities were measured. Results Subjects with BD depression at baseline presented a significant increase in CAT (p = 0.005) and GPx (p < 0.001) levels, with lower SOD/CAT ratio (p = 0.001) and no changes on SOD or TBARS compared to healthy controls. Regarding therapeutics, lithium only induced a decrease in TBARS (p = 0.023) and SOD (p = 0.029) levels, especially in BDII. Finally, TBARS levels were significantly lower at endpoint in lithium responders compared to non-responders (p = 0.018) with no difference in any biomarker regarding remission. Conclusion The present findings suggest a reactive increase in antioxidant enzymes levels during depressive episodes in early stage BD with minimal prior treatment. Also, decreased lipid peroxidation (TBARS) levels were observed, associated with lithium’s clinical efficacy. Overall, these results reinforce the role for altered oxidative stress in the pathophysiology of BD and the presence of antioxidant effects of lithium in the prevention of illness progression and clinical efficacy.

Effects of Lithium Monotherapy for Bipolar Disorder on Gene Expression in Peripheral Lymphocytes

“…Lithium efficacy has been previously reported to be associated with decreased lipid peroxidation [32]. …”

A longitudinal proton magnetic resonance spectroscopy study investigating oxidative stress as a result of alcohol and tobacco use in youth with bipolar disorder

“…Although there was no significant difference in patients that remained on or off medications, there is the possibility that some medications may have influenced ACC-GSH. For example, lithium has been shown to have neuroprotective effects (de Sousa et al, 2014). A larger sample size would allow us to look further into the effect of medications on this relationship.…”

Thiobarbituric acid reactive substances (TBARS) is a state biomarker of oxidative stress in bipolar patients in a manic phase

“…GPx can scavenge peroxides and hydroxyl radicals with glutathione (Chance et al, 1979). Levels of GPx were increased in some reports of euthymic and depressed patients with bipolar disorder (Andreazza et al, 2007a;de Sousa et al, 2014), and showed no significant changes in other reports (Andreazza et al, 2008a(Andreazza et al, , 2009Raffa et al, 2012).…”