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.

Keywords: Bipolar Disorder; Depression; Lithium; Neuroprotection; Oxidative stress.

Fig. 1

OxS parameters in patients with bipolar disorder in a depressive episode before (black bar) and after lithium treatment (grey bar) compared to healthy controls (white bar): A) TBARS– Thiobarbituric Acid Reactive Substances; B) SOD – Superoxide Dismutase; C) CAT – Catalase; D) SOD/CAT ratio, and E) GPx – Glutathione Peroxidase; *p < 0.05, **p < 0.01.

Fig. 2

A) Endpoint thiobarbituric acid reactive substances (TBARS) levels in responders compared with non-responders to lithium treatment. B) Endpoint TBARS levels in Bipolar Disorder I compared to Bipolar Disorder II; *p < 0.05.