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

Abstract

Aim: Accumulated 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. Methods: We 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. Results: Compared 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). Conclusion: The 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.

Therapeutic Interventions to Mitigate Mitochondrial Dysfunction and Oxidative Stress–Induced Damage in Patients with Bipolar Disorder

“…BDNF is important for the development, plasticity, and survival of neurons [75,158,159]. Six meta-analyses found decreased BDNF levels in BD patients compared with both healthy individuals and patients with unipolar depression [52, [160][161][162][163].…”

“…A similar metaanalysis consisting of 35 studies and 3798 research participants reported that BD patients exhibited lower peripheral BDNF levels compared with healthy controls [52]. Another study measured mtDNA copy number in leukocytes, plasma BDNF level, and antioxidant enzyme activity in 97 BD patients and 31 healthy controls [158]. BDNF level, mtDNA copy number, and GPX activity in the BD patients were significantly lower than those in the controls [158].…”

Concepts of Neuroinflammation and Their Relationship With Impaired Mitochondrial Functions in Bipolar Disorder

“…As related above, studies in animals and humans have reported that increased oxidative damage reduced BDNF expression. However, BDNF has been shown to stimulate the expression and activities of GSH-Px and SOD; resulting in reduced oxidative damage (He and Katusic, 2012 ; Valvassori et al, 2015 ; Wang et al, 2020 ).…”

Molecular Biomarkers of Electroconvulsive Therapy Effects and Clinical Response: Understanding the Present to Shape the Future

“…BDNF represents the most abundant neurotrophin in the brain; during the development of the central nervous system, it promotes the growth of axons and the maturation of synaptic connections, whereas in the adult brain, it plays key roles in mechanisms of maintenance, stabilization, and neuroplasticity [ 29 ]. Moreover, there is evidence showing associations between BDNF and oxidative stress markers, with increased oxidative stress damage responses coupled with decreased BDNF levels, indicating that BDNF may play a protective role against oxidative damage in neurons [ 30 ]. This neurotrophin can also be found in the peripheral blood, where it is mostly stored in platelets [ 31 ].…”