Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
Huashan Hospital, Fudan University, 200040, China.
J Affect Disord. 2024 Oct 15;363:563-571. doi: 10.1016/j.jad.2024.07.024. Epub 2024 Jul 25.
Previous studies have shown a lower hemodynamic response in patients with major depressive disorder (MDD) during cognitive tasks. However, the mechanism underlying impaired hemodynamic and neural responses to cognitive tasks in MDD patients remains unclear. Succinate dehydrogenase (SDH) is a key biomarker of mitochondrial energy generation, and it can affect the hemodynamic response via the neurovascular coupling effect. In the current study, cerebral hemodynamic responses were detected during verbal fluency tasks (VFTs) via functional near-infrared spectroscopy (fNIRS) and SDH protein levels were examined in serum from MDD patients to quickly identify whether these hemodynamic alterations were related to mitochondrial energy metabolism.
Fifty patients with first-episode drug-naïve MDD and 42 healthy controls (HCs) were recruited according to inclusion and exclusion criteria. The 17-item Hamilton Depression Rating Scale (17-HDRS), Hamilton Anxiety Rating Scale (HAMA) and Inventory of Depressive Symptomatology-Self Report (IDS-SR) were used to assess the clinical symptoms of the patients. All participants underwent fNIRS measurements to evaluate cerebral hemodynamic responses in the frontal and temporal cortex during VFTs; moreover, SDH protein levels were measured using an enzyme-linked immunosorbent assay.
Activation in the frontal-temporal brain region during the VFTs was lower in patients with MDD than in HCs. The SDH level in the serum of MDD patients was also significantly lower than that in HCs (p = 0.003), which significantly affected right lateral frontal (p = 0.025) and right temporal (p = 0.022) lobe activation. Both attenuated frontal-temporal activation during the VFTs (OR = 1.531) and lower SDH levels (OR = 1.038) were risk factors for MDD.
MDD patients had lower cerebral hemodynamic responses to VFTs; this was associated with mitochondrial dysfunction, as indicated by SDH protein levels. Furthermore, attenuated hemodynamic responses in frontotemporal regions and lower SDH levels increased the risk for MDD.
The sample size is relatively small. SDH protein levels in peripheral blood may not necessarily reflect mitochondrial energy generation in the central nervous system.
先前的研究表明，在认知任务中，重度抑郁症（MDD）患者的血液动力学反应较低。然而，MDD 患者对认知任务的血液动力学和神经反应受损的机制尚不清楚。琥珀酸脱氢酶（SDH）是线粒体能量产生的关键生物标志物，它可以通过神经血管耦合效应影响血液动力学反应。在本研究中，通过功能近红外光谱（fNIRS）检测言语流畅性任务（VFT）期间的大脑血液动力学反应，并检查 MDD 患者血清中的 SDH 蛋白水平，以快速确定这些血液动力学改变是否与线粒体能量代谢有关。
根据纳入和排除标准，招募了 50 名首发、未用药的 MDD 患者和 42 名健康对照者（HCs）。采用 17 项汉密尔顿抑郁评定量表（17-HDRS）、汉密尔顿焦虑评定量表（HAMA）和抑郁症状自评量表-自我报告（IDS-SR）评估患者的临床症状。所有参与者均接受 fNIRS 测量，以评估 VFT 期间额颞皮质的大脑血液动力学反应；此外，还使用酶联免疫吸附测定法测量 SDH 蛋白水平。
与 HCs 相比，MDD 患者在 VFT 期间额颞区的激活较低。MDD 患者血清中的 SDH 水平也明显低于 HCs（p=0.003），这显著影响右侧外侧额叶（p=0.025）和右侧颞叶（p=0.022）的激活。VFT 期间额叶-颞叶激活减弱（OR=1.531）和 SDH 水平降低（OR=1.038）均是 MDD 的危险因素。
MDD 患者在进行 VFT 时大脑血液动力学反应较低；这与 SDH 蛋白水平所示的线粒体功能障碍有关。此外，额颞区血液动力学反应减弱和 SDH 水平降低增加了 MDD 的风险。
样本量相对较小。外周血中的 SDH 蛋白水平不一定反映中枢神经系统的线粒体能量产生。
