Wang Dong, Li Hong, Du Xiangdong, Zhou Jun, Yuan Liu, Ren Honghong, Yang Xiaonan, Zhang Guangya, Chen Xiaogang
Department of Geriatric Psychiatry, Suzhou Mental Health Center, Suzhou Guangji Hospital, the Affiliated Guangji Hospital of Soochow University, Suzhou, China.
Department of Psychiatry, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Front Psychiatry. 2020 Sep 11;11:514658. doi: 10.3389/fpsyt.2020.514658. eCollection 2020.
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.
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.
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).
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.
越来越多的证据表明,神经营养因子失调、氧化应激损伤和线粒体功能障碍与双相情感障碍(BD)有关;然而,它们在双相情感障碍中的实际作用尚不清楚。研究这三个系统之间可能的相互作用,对于理解这一复杂过程很有必要。
我们测量了双相情感障碍患者(n = 97)和健康对照者(n = 31)的血浆脑源性神经营养因子(BDNF)水平、白细胞线粒体DNA拷贝数(mtDNAcn)以及抗氧化酶活性。进行方差分析和线性回归分析,以探讨mtDNAcn、抗氧化酶和BDNF之间的相互作用。
与健康对照者相比,双相情感障碍患者的谷胱甘肽过氧化物酶活性、BDNF水平和mtDNA含量显著降低,锰超氧化物歧化酶(MnSOD)活性显著升高(均p < 0.05)。回归分析显示,MnSOD活性对BDNF有中等程度的影响(β = 0.23,t = 8.5,p = 0.001)。铜锌超氧化物歧化酶和总超氧化物歧化酶活性与抑郁患者的汉密尔顿抑郁量表评分显著相关(r = -0.38,p = 0.013;r = -0.35,p = 0.022)。出乎意料的是,我们发现双相情感障碍患者的mtDNA含量与BDNF之间无显著相关性(p > 0.05)。
这些发现与我们的假设一致,即抗氧化酶、mtDNAcn和外周BDNF异常可能参与双相情感障碍的病程。外周BDNF、抗氧化酶活性和mtDNAcn之间存在显著相关性,表明氧化应激、线粒体功能和BDNF在双相情感障碍中可能相互影响。