1)宁波大学医学部,宁波 315211;2)宁波大学附属康宁医院,宁波 315201
浙江省自然科学基金(LY21H090003),浙江省医药卫生(2019KY628),宁波市自然科学基金(2023J029)和宁波市重点研发计划暨“揭榜挂帅”(2023Z175)资助项目。
1)Health Science Center, Ningbo University, Ningbo 315211, China;2)Department of psychiatry, Affiliated Kangning Hospital of Ningbo University, Ningbo 315201, China
This work was supported by grants from Zhejiang Provincial Natural Science Foundation (LY21H090003), Medical Health Science and Technology Project of Zhejiang Provincial Health Commission (2019KY628), Ningbo Natural Science Foundation (2023J029), Ningbo Key Research and Development Program (Unveiling and Commanding Projects Mechanism) (2023Z175).
改良电休克治疗(modified electro-convulsive therapy, MECT)?是抑郁症的有效治疗手段,但伴随的一过性记忆损伤限制了其临床应用。近年来,多模态磁共振成像(magnetic resonance imaging, MRI)为探索MECT的神经机制提供了新视角。MECT可广泛影响脑结构和功能,包括前额叶、海马体、杏仁核等脑区灰质体积增加,以及默认模式网络(default mode network, DMN)、突显网络和中央执行网络(central executive network,CEN)的功能连接改变。其中,右侧海马体积增长、DMN核心节点(如后扣带回-内侧前额叶)连接正常化、背外侧前额叶(属于CEN)到右角回(属于DMN)的有效连接增强等,与抗抑郁疗效相关;而左侧海马及齿状回体积增长、DMN连接异常增强、左丘脑-楔前叶(属于DMN)功能连接减弱等,则与记忆损伤相关。海马体可能是MECT双重效应的关键靶点,但现有证据尚不能确定其变化是否同时导致抑郁缓解和记忆损伤。临床观察显示,抑郁改善与记忆损伤程度往往不相关,提示不同海马亚区可能分别介导不同效应:右侧海马体积增加与情绪改善相关,左侧齿状回体积则与记忆功能受损相关。此外,前额叶增厚、纹状体铁沉积减少、DMN核心节点连接恢复和CEN-DMN的功能连接重建等改变与抗抑郁相关,DMN内连接异常增强及跨网络交互则可能干扰语义记忆。目前研究受限于样本量不足和方法学差异,难以定论MECT的双重机制。未来需结合大样本、多时间点随访、高场强MRI及多模态分析,深入探究海马体结构-功能协同效应及网络耦合机制,以精准区分疗效与副作用靶点,优化临床决策。
Modified electro-convulsive therapy (MECT) is one of the most potent treatments for major depressive disorder (MDD). However, it remains a second-line option due to significant side effects, such as transient memory loss. The relationship between therapeutic efficacy and cognitive impairment warrants further investigation to develop improved treatment regimens. In this review, we examine recent evidence from magnetic resonance imaging (MRI) studies aiming to identify structural and functional brain changes specifically associated with both the antidepressant effects and the amnesic outcomes of MECT. MECT induces widespread alterations across multiple brain systems. Increases in gray matter volume (GMV) have been observed in the prefrontal, temporal, and parietal cortices, as well as in subcortical regions such as the hippocampus (HP), amygdala, and striatum. Strengthening of myelination has also been reported along the dorsolateral prefrontal-limbic pathways. Functional changes include increased spontaneous neural activity in prefrontal areas, reorganization of intrinsic connectivity within the default mode network (DMN), and altered functional connectivity (FC) among the DMN, salience network (SN), and central executive network (CEN). Correlational studies have identified structural and functional alterations linked to antidepressant efficacy, including right hippocampal volume enlargement, prefrontal cortical thickening, reduced iron deposition in the striatum, decreased FC within certain DMN nodes, and enhanced effective connectivity from the dorsolateral prefrontal cortex (DLPFC) to the right angular gyrus. In contrast, the amnesic effects have been associated with increased volumes in the left hippocampus and bilateral dentate gyrus; enhanced FC in the left angular gyrus and left posterior cingulate cortex (PCC); increased FC between the right ventral anterior insula and DLPFC; and reduced FC in the left thalamus and bilateral precuneus. Changes in the hippocampus appear to correlate with both antidepressant efficacy and memory impairment. Clinical studies have found no significant correlation between the severity of memory impairment and the reduction in depressive symptoms, suggesting that the therapeutic and adverse effects may arise from distinct regional or subregional mechanisms. Supporting this hypothesis, recent findings show that increased right hippocampal volume is significantly associated with reduced depression scores, whereas increased volume in the left dentate gyrus correlates with declines in delayed recall performance. Additionally, enhanced connectivity between the anterior hippocampus and middle occipital gyrus (MOG) has been linked to mood improvement, while decreased FC between the mid-hippocampus and angular gyrus has been associated with impairments in memory integration. In conclusion, current evidence suggests that the antidepressant and memory-impairing effects of MECT may localize to distinct hippocampal subregions. These effects likely result from differential modulation of local neural activity and functional connectivity, leading to divergent behavioral outcomes. Given that both effects may originate in deep and spatially constrained structures such as the hippocampus, small-sample studies and conventional methodologies may fail to differentiate them effectively. Future research should employ large-scale, longitudinal designs utilizing high-field MRI and multimodal neuroimaging to characterize MECT-induced structure-function coupling in the hippocampus and its integration at the network level. Additionally, multiscale analyses spanning molecular, circuit, and network dimensions would be beneficial.
沈若冰,沈雯雯,高树贵.改良电休克治疗对抑郁症疗效与副作用的神经影像机制[J].生物化学与生物物理进展,,():
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