Mitochondrial DNA Copy Number Raises the Potential of Left Frontopolar Hemodynamic Response as a Diagnostic Marker for Distinguishing Bipolar Disorder From Major Depressive Disorder
Mitochondrial DNA Copy Number Raises the Potential of Left Frontopolar Hemodynamic Response as a Diagnostic Marker for Distinguishing Bipolar Disorder From Major Depressive Disorder
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DOI：
10.3389/fpsyt.2019.00312
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发表时间：
2019-05
影响因子：
4.7
通讯作者：
N. Tsujii;Ikuo Otsuka;S. Okazaki;M. Yanagi;Shusuke Numata;Naruhisa Yamaki;Yoshihiro Kawakubo;O. Shirakawa;A. Hishimoto
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文献类型：
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作者：
N. Tsujii;Ikuo Otsuka;S. Okazaki;M. Yanagi;Shusuke Numata;Naruhisa Yamaki;Yoshihiro Kawakubo;O. Shirakawa;A. Hishimoto
背景：由于缺乏标记物，双相情感障碍（BD）和重性抑郁障碍（MDD）的诊断依赖于临床症状评估。然而，BD的抑郁情绪状态和MDD的抑郁症状往往难以区分，这导致误诊，从而导致治疗不足。先前的研究表明，通过近红外光谱（NIRS）测量的左额极皮质的血流动力学反应在BD和MDD之间存在差异;这些血流动力学反应与线粒体代谢改变相关;线粒体DNA拷贝数（mtDNAn）是线粒体功能障碍的指标，在BD患者中倾向于减少，在MDD患者中倾向于增加。在这项研究中，我们证实了mtDNA在BD和MDD中的趋势相反。然后，我们确定是否mtDNAc n可以提高近红外光谱作为诊断标志物区分BD和MDD的效用。方法：检测58例健康对照者、79例BD患者和44例MDD患者外周血中mtDNAc n。在语言流畅性任务（VFT）中，24例BD患者和44例MDD患者（年龄和抑郁严重程度相匹配）的局部血流动力学反应进行了监测。结果：BD患者mtDNAc n低于对照组，MDD患者mtDNAc n高于对照组。左额极区在BD和MDD组之间的平均VFT相关氧合血红蛋白变化中表现出最显著的差异。多变量logistic回归分析显示，年龄、性别、左额极区血流动力学反应和mtDNAcn对区分BD和MDD具有较高的准确性（曲线下面积= 0.917; 95%置信区间= 0.849-0.985）。对于BD组，我们观察到左额极区的血流动力学反应与mtDNA之间呈正相关，而对于MDD组，我们观察到负相关。结论：我们的研究结果表明，BD或MDD的血流动力学反应和线粒体功能障碍之间的关联在区分BD和MDD的病理生理机制中起着重要作用。
Background: Given a lack of markers, diagnoses of bipolar disorder (BD) and major depressive disorder (MDD) rely on clinical assessment of symptoms. However, the depressive mood states of BD and depressive symptoms of MDD are often difficult to distinguish, which leads to misdiagnoses, which in turn leads to inadequate treatment. Previous studies have shown that the hemodynamic responses of the left frontopolar cortex measured by near-infrared spectroscopy (NIRS) differ between BD and MDD; these hemodynamic responses are associated with altered mitochondrial metabolism; and mitochondrial DNA copy number (mtDNAcn), an index of mitochondrial dysfunction, tends to decrease in BD and increase in MDD patients. In this study, we confirmed that mtDNAcn trends in opposite directions in BD and MDD. We then determined whether mtDNAcn could enhance the utility of NIRS as a diagnostic marker to distinguish between BD and MDD. Methods: We determined mtDNAcn in peripheral blood samples from 58 healthy controls, 79 patients with BD, and 44 patients with MDD. Regional hemodynamic responses during a verbal fluency task (VFT) in 24 BD patients and 44 MDD patients, matched by age and depression severity, were monitored using NIRS. Results: Measurements of mtDNAcn were lower in BD patients and higher in MDD patients than in controls. The left frontopolar region exhibited the most significant differences in mean VFT-related oxy-Hb changes between the BD and MDD groups. Multivariate logistic regression analysis with variables including age, sex, hemodynamic response of the left frontopolar region, and mtDNAcn showed high accuracy for distinguishing BD from MDD (area under the curve = 0.917; 95% confidence interval = 0.849–0.985). For the BD group, we observed a positive correlation between hemodynamic responses in the left frontopolar region and mtDNAcn, while for the MDD group, we observed a negative correlation. Conclusions: Our findings suggest that the association between hemodynamic response and mitochondrial dysfunction in BD or MDD plays an important role in differentiating the pathophysiological mechanisms of BD from those of MDD.