Circulating Brain-Derived Neurotrophic Factor, Antioxidant Enzymes Activities, and Mitochondrial DNA in Bipolar Disorder: An Exploratory Report.

Dong Wang,Liu Yuan,Honghong Ren,Guangya Zhang,Xiangdong Du,Hong Li,Xiaonan Yang,Jun Zhou,Xiaogang Chen

doi:10.3389/fpsyt.2020.514658

Abstract

AimAccumulated evidence indicates that neurotrophin deregulations, oxidative stress injury, and mitochondrial dysfunction have been involved in bipolar disorder (BD); however, their real roles in BD are unclear. Investing the possible interaction between three systems is worthwhile understanding this complex process.MethodsWe measured plasma brain-derived neurotrophic factor (BDNF) level, leukocytes mitochondrial DNA copy number (mtDNAcn), and activities of antioxidant enzymes in BD patients (n = 97) and healthy controls (n = 31). Analysis of variance and linear regression analyses were performed to explore the interaction between mtDNAcn, antioxidant enzymes, and BDNF.ResultsCompared with healthy controls, there were significant decreases of glutathione peroxidase activity, BDNF levels, and mtDNA content, significant increases of manganese superoxide dismutase (MnSOD) activity among BD patients (all p < 0.05). Regression analysis showed MnSOD activity had a moderate effect on BDNF (beta = 0.23, t = 8.5, p = 0.001). Copper zinc SOD and total SOD activity were significantly correlated with Hamilton Depression Scale scores in depressive patients (r = −0.38, p = 0.013; r = −0.35, p = 0.022). Unexpectedly, we observed no significant correlation between mtDNA content and BDNF in BD patients (p > 0.05).ConclusionThe findings coincide with our hypothesis that abnormal antioxidant enzymes, mtDNAcn, and peripheral BDNF may be involved in the course of BD. There were significant correlations between peripheral BDNF, antioxidant enzyme activities and mtDNAcn, suggesting that oxidative stress, mitochondrial function, and BDNF may influence each other in BD.

Highlights

Bipolar disorder (BD) is a debilitating and progressive psychiatric disorder, characterized by recurrent episodes of mania and depression, affecting more than 1% of the population worldwide [1]
No significant differences in the three groups were found in terms of age, gender, smoking, and body mass index (BMI)
The results indicated that there were negative correlations between CuZnSOD activity, total SOD (TSOD) activity, and Hamilton Depression Scale (HAMD) scores (r = −0.38, p = 0.013; r = −0.35, p = 0.022, respectively) (Figures 2A, B)

Summary

Introduction

Bipolar disorder (BD) is a debilitating and progressive psychiatric disorder, characterized by recurrent episodes of mania and depression, affecting more than 1% of the population worldwide [1]. It is known that BD has been supposed to be a psychiatric disease, but rather a multi-system disorder [4], involving multiple factors, such as genetic, environmental, and social background; neurotrophin deregulations, oxidative stress injury, and mitochondrial dysfunction [5, 6]. These potential biomarkers are very important to understand the pathophysiology of BD, and develop new treatment strategies. Brain-derived neurotropic factor (BDNF), an important member of neurotrophins, plays a crucial role in neurodevelopment, neuronal plasticity, and survival. BDNF has been reported to be involved in the pathology of BD, the role of BDNF in the genesis and development of BD is still not well understood

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