Liu Xiang, Li Lifeng, Li Haijun, Deng Yingke, Liu Yumeng, Peng Dechang, Wu Guojiang, Zhou Xueming
Jiangxi Provincial Key Laboratory for Precision Pathology and Intelligent Diagnosis, Department of Radiology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, China.
Jiangxi Provincial Key Laboratory for Precision Pathology and Intelligent Diagnosis, Department of Radiology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, China.
J Affect Disord. 2025 Sep 1:120156. doi: 10.1016/j.jad.2025.120156.
Dysfunction in amygdala networks has been implicated in major depressive disorder (MDD). Pharmacological treatments, such as esketamine and sertraline, are believed to exert their antidepressant effects by modulating amygdalar activity. This study aimed to investigate the relationship between changes in dynamic functional connectivity (dFC) within amygdala subregions and treatment outcomes, with a focus on identifying potential neuroimaging markers.
Twenty-eight patients with MDD received six intravenous infusions of esketamine (0.25 mg/kg) combined with 2 weeks of sertraline treatment. Mood and cognitive recovery were assessed using the HAMA, HAMD, BSI, and MoCA. Seed-based dFC analysis of resting-state MRI focused on the dorsal amygdala (DA), medial amygdala (MA), and ventrolateral amygdala (VA).
All patients demonstrated positive responses to treatment, with significant reductions in HAMA and HAMD scores, as well as improvements in MoCA scores and a decrease in suicidal ideation. Following treatment, static functional connectivity (sFC) was reduced between the right DA and paracentral lobule, the left VA and multiple regions (including the lentiform nucleus, thalamus, medial prefrontal cortex, inferior parietal lobule, precentral gyrus, and superior parietal lobule), and the right VA and middle frontal gyrus. Conversely, dFC was significantly increased between the right DA and cuneus/superior parietal lobule, and between the left VA and superior parietal lobule. A decrease in dFC was also observed between the left MA and superior temporal gyrus. Correlation analysis showed that dFC between the left MA and superior temporal gyrus was positively correlated with HAMA score.
The combined use of esketamine and sertraline limits the ability to differentiate their individual effects. A significant proportion of the patients were adolescents, with only a few adults, which may influence the age-related response to treatment. The study utilized the lowest effective dose of esketamine, thereby leaving the dose-response relationships unexamined. The small sample size further restricts the statistical power of the findings, highlighting the need for larger studies to validate these results.
Altered resting-state and dFC in amygdala subregions may play a role in the mechanisms by which the combination of esketamine and sertraline alleviates depressive symptoms, primarily involving the sensorimotor and default mode networks. Together, the sFC and dFC analyses provide an integrated perspective on depression-related connectivity changes and offer potential targets for treatment.
杏仁核网络功能障碍与重度抑郁症（MDD）有关。艾司氯胺酮和舍曲林等药物治疗被认为是通过调节杏仁核活动发挥抗抑郁作用。本研究旨在探讨杏仁核亚区域内动态功能连接（dFC）变化与治疗结果之间的关系，重点是识别潜在的神经影像学标志物。
28例MDD患者接受6次静脉注射艾司氯胺酮（0.25mg/kg）并联合2周舍曲林治疗。使用汉密尔顿焦虑量表（HAMA）、汉密尔顿抑郁量表（HAMD）、症状自评量表（BSI）和蒙特利尔认知评估量表（MoCA）评估情绪和认知恢复情况。基于静息态MRI的种子点dFC分析聚焦于背侧杏仁核（DA）、内侧杏仁核（MA）和腹外侧杏仁核（VA）。
所有患者对治疗均表现出阳性反应，HAMA和HAMD评分显著降低，MoCA评分改善，自杀观念减少。治疗后，右侧DA与中央旁小叶之间、左侧VA与多个区域（包括豆状核、丘脑、内侧前额叶皮质、顶下小叶、中央前回和顶上小叶）之间以及右侧VA与额中回之间的静态功能连接（sFC）降低。相反，右侧DA与楔叶/顶上小叶之间以及左侧VA与顶上小叶之间的dFC显著增加。左侧MA与颞上回之间的dFC也降低。相关性分析表明，左侧MA与颞上回之间的dFC与HAMA评分呈正相关。
艾司氯胺酮和舍曲林联合使用限制了区分它们各自作用的能力。相当一部分患者为青少年，仅有少数成年人，这可能影响与年龄相关的治疗反应。本研究使用了艾司氯胺酮的最低有效剂量，因此未研究剂量反应关系。小样本量进一步限制了研究结果的统计效力，突出了需要更大规模研究来验证这些结果。
杏仁核亚区域静息态和dFC的改变可能在艾司氯胺酮和舍曲林联合使用减轻抑郁症状的机制中起作用，主要涉及感觉运动和默认模式网络。sFC和dFC分析共同提供了关于抑郁症相关连接变化的综合观点，并为治疗提供了潜在靶点。
