Recent studies have suggested that mitochondrial dysfunction and dysregulated neuroinflammatory pathways are involved in the pathophysiology of major depressive disorder (MDD). Here, we aimed to assess the differences in markers of mitochondrial dynamics, mitophagy, general autophagy, and apoptosis in peripheral blood mononuclear cells (PBMCs) of MDD patients (n = 77) and healthy controls (HCs, n = 24). Moreover, we studied inflammation engagement as a moderator of mitochondria dysfunctions on the severity of depressive symptoms. We found increased levels of Mfn-2 (p < 0.001), short Opa-1 (S-Opa-1) (p < 0.001) and Fis-1 (p < 0.001) in MDD patients, suggesting an increase in the mitochondrial fragmentation. We also found that MDD patients had higher levels of Pink-1 (p < 0.001), p62/SQSTM1 (p < 0.001), LC3B (p = 0.002), and caspase-3 active (p = 0.001), and lower levels of parkin (p < 0.001) compared with HCs. Moreover, we showed that that MDD patients with higher CRP levels had higher levels of Mfn-2 (p = 0.001) and LC3B (p = 0.002) when compared with MDD patients with low CRP. Another notable finding was that the severity of depressive symptoms in MDD is associated with changes in protein levels in pathways related to mitochondrial dynamics and mitophagy, and can be dependent on the inflammatory status. Overall, our study demonstrated that a disruption in the mitochondrial dynamics network could initiate a cascade of abnormal changes relevant to the critical pathological changes during the course of MDD and lead to poor outcomes.

最近的研究表明，线粒体功能障碍和神经炎症通路失调与重度抑郁症 (MDD) 的病理生理学有关。在这里，我们旨在评估 MDD 患者 ( n  = 77) 和健康对照 (HCs，n  = 24)的外周血单核细胞 (PBMC) 的线粒体动力学、线粒体自噬、一般自噬和凋亡标志物的差异。此外，我们研究了炎症参与作为线粒体功能障碍对抑郁症状严重程度的调节剂。我们发现 Mfn-2 ( p  < 0.001)、short Opa-1 (S-Opa-1) (p < 0.001) 和 Fis-1 ( p < 0.001) 在 MDD 患者中，表明线粒体断裂增加。我们还发现 MDD 患者的 Pink-1 ( p  < 0.001)、p62/SQSTM1 ( p  < 0.001)、LC3B ( p  = 0.002) 和 caspase-3 活性 ( p  = 0.001) 水平较高，而parkin ( p  < 0.001) 与 HC 相比。此外，我们发现 CRP 水平较高的 MDD 患者具有较高水平的 Mfn-2 ( p  = 0.001) 和 LC3B ( p = 0.002) 与低 CRP 的 MDD 患者相比。另一个值得注意的发现是，MDD 中抑郁症状的严重程度与线粒体动力学和线粒体自噬相关通路中蛋白质水平的变化有关，并且可能取决于炎症状态。总的来说，我们的研究表明，线粒体动力学网络的破坏可能引发与 MDD 过程中关键病理变化相关的一系列异常变化，并导致不良结果。