rTMS对难治性抑郁症的治疗和预测机制的静息态脑功能研究

The management of treatment-resistant depression (TRD) is an important but toublesome issue in clinics. Repetitive transcranial magnetic stimulation (rTMS) provides one possible solution. However, its antidepressant effect is moderate and cross-individual variation is quite large. In this study, TRD patients will be treated with real-rTMS or sham-rTMS through double-blinded, randomized controlled trials, and the actual stimulated target of each individual will be marked with a vitamin E capsule. Clinical symptoms and resting-state functional magnetic resonance imaging will be measured at 3 time points (pre-treatment, post-treatment and 4 weeks post-treatment). Based on the functional connectivity within and between the brain networks of DMN, CEN and SN in TRD, we will explore the association between the dynamic network changes and symptom changes after rTMS treatment at two post-treatment time points to elucidate the therapeutic mechanism of rTMS. In addition, based on the coordinate of the actual stimulated target, we will construct individual brain function connectivity maps, and analyze the relationship between the baseline connectivity strength and the treatment-induced brain network changes, as well as the degree of symptom improvement for separate dimensions, based on the baseline functional connectivity data. The project will advance our practice for selecting the targets for optimizing the therapeutic effect of rTMS, which has important scientific significance and clinical value.

难治性抑郁症（TRD）的治疗是临床上棘手而重要的问题，重复经颅磁刺激（rTMS）是可选手段之一，然而其抗抑郁效应仍不够理想，且个体间的疗效差异大。本研究拟通过随机对照试验对TRD患者进行真性、假性rTMS治疗，并用维生素E胶囊标记个体的实际刺激靶点。于治疗前、治疗结束时、结束后4周这三个时间点检测临床症状以及静息态功能磁共振。基于TRD的脑网络（DMN、CEN、SN）内部和之间的功能连接，探测其在rTMS治疗后的动态变化和症状改变的相关性，明确rTMS的治疗机制。同时，基于个体的实际刺激靶点坐标，建立脑功能连接图谱，探寻基线脑功能连接强度与脑网络改变之间的相关性；并进一步探索与不同症状维度的疗效的相关性，明确刺激靶点位置对rTMS抗抑郁效应的预测机制。本项目为选择最佳的刺激靶点位置，优化rTMS疗效提供了理论依据，具有重要的科学意义和临床价值。

抑郁症是一种常见的精神障碍之一，并造成严重的疾病负担。rTMS作为一种有效的治疗抑郁症的无创脑刺激手段，得到广泛的临床应用，但同时其疗效的个体差异大，如何更加准确地选择刺激靶点位置是一个重点和难点。本课题收集了27例抑郁症患者组基线状态下和27例正常对照组的静息态功能磁共振数据，并对抑郁症患者进行了rTMS治疗两周，再次复查抑郁症组的脑影像数据并评估其疗效。统计结果显示，抑郁症患者基线状态下的中央执行网络（CEN）的整体功能连接密度（FCD）显著低于正常对照。经过rTMS治疗后，CEN的整体FCD有显著提高，但是该变化与抗抑郁效应无显著的相关性。同时，本研究发现当左侧DLPFC以CEN枢纽节点的方式来定位时，基线状态下的左侧DLPFC-双侧岛叶的功能连接强度与rTMS的临床疗效显著正相关(左侧岛叶r = 0.66, p <0.001; 右侧岛叶r = 0.65, p <0.001)。DTI分析显示，左侧DLPFC-左侧岛叶之间的结构连接的平均FA值与rTMS治疗后的汉密尔顿抑郁量表减分值呈显著的正相关(r=0.458, p=0.028)。本研究提示，与脑岛有最强功能和结构连接的左侧DLPFC区域可能用作个体化的候选刺激靶点之一，从而进一步提高rTMS的临床疗效。

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