经颅磁刺激治疗对抑郁症患者杏仁核及海马亚区体积的影响

doi:10.3969/j.issn.1674-8115.2025.04.005

上海交通大学学报（医学版） ›› 2025, Vol. 45 ›› Issue (4): 434-442.doi: 10.3969/j.issn.1674-8115.2025.04.005

经颅磁刺激治疗对抑郁症患者杏仁核及海马亚区体积的影响

王思睿¹^,², 孔盖², 李惠², 钱禛颖², 崔慧茹², 唐莺莹¹^,²()

^1.上海交通大学医学院附属精神卫生中心影像数据中心，上海 200030
^2.上海交通大学医学院附属精神卫生中心脑电影像室，上海 200030

收稿日期:2024-12-10 接受日期:2024-12-31 出版日期:2025-04-28 发布日期:2025-04-28
通讯作者: 唐莺莹 E-mail:yytang@smhc.org.cn
作者简介:王思睿（1999—），女，硕士生；电子信箱：wangsr0305@163.com。
基金资助:
国家科技创新2030项目(2022ZD0212800);上海市自然科学基金原创探索项目(21ZR1481500);上海市教育委员会高峰高原学科建设计划(20191836)

Impact of transcranial magnetic stimulation therapy on the volumes of amygdala and hippocampal subfields in patients with major depressive disorder

WANG Sirui¹^,², KONG Gai², LI Hui², QIAN Zhenying², CUI Huiru², TANG Yingying¹^,²()

^1.Neuroimaging Core, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
^2.Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China

Received:2024-12-10 Accepted:2024-12-31 Online:2025-04-28 Published:2025-04-28
Contact: TANG Yingying E-mail:yytang@smhc.org.cn
Supported by:
Science Technology Innovation 2030-Major Projects(2022ZD0212800);National Natural Science Foundation of Shanghai(21ZR1481500);Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support(20191836)

摘要/Abstract

摘要：

目的·比较抑郁症患者接受经颅磁刺激（transcranial magnetic stimulation，TMS）治疗前后杏仁核及海马亚区体积的纵向变化，并探讨其与TMS抗抑郁与抗焦虑疗效的相关性。方法·纳入2018年1月—2023年8月于上海交通大学医学院附属精神卫生中心门诊就诊的抑郁症患者58例，使用汉密尔顿抑郁量表（Hamilton Depression Scale，HAMD）、蒙哥马利-阿斯伯格抑郁量表（Montgomery-Asberg Depression Rating Scale，MADRS）和汉密尔顿焦虑量表（Hamilton Anxiety Scale，HAMA）评估患者基线及TMS治疗后的临床抑郁和焦虑症状。所有被试在基线磁共振扫描之后接受干预左侧背外侧前额叶（dorsolateral prefrontal cortex，DLPFC）的TMS治疗，频率10 Hz，共20次。治疗结束当日进行1次磁共振随访。利用FreeSurfer v6.0.0软件对采集到的杏仁核及海马图谱进行亚区分割并计算各亚区体积，使用双因素方差分析对亚区体积进行纵向比较。控制年龄、性别和颅内容积，对抑郁症患者杏仁核和海马亚区体积与基线临床量表（HAMD、MADRS和HAMA）得分进行偏相关分析，并分析体积变化显著的的脑区中体积变化率与TMS干预前后临床量表（HAMD、MADRS和HAMA）减分的相关性。结果·经过TMS治疗后，抑郁症患者右侧杏仁核中央核的体积增大，差异具有统计学意义（t=-2.441，P=0.018）；海马亚区除双侧海马伞体积下降外，部分海马亚区及总海马体积均有所增加（P<0.05）。基线时，未发现患者杏仁核及海马亚区体积与抑郁和焦虑症状存在显著相关性；仅在TMS治疗有效的患者中，发现左侧海马尾部的体积变化率与临床焦虑症状减分呈正相关（HAMA：r=0.334，P=0.044）。结论·TMS高频干预左侧DLPFC可能引起右侧杏仁核中央核及双侧部分海马亚区体积增大，并且TMS治疗有效者的左侧海马尾部体积变化率与TMS抗焦虑疗效之间存在联系，提示TMS高频干预左侧DLPFC可能引起右侧杏仁核中央核及双侧部分海马亚区的神经可塑性改变。

关键词: 抑郁症, 经颅磁刺激, 杏仁核亚区, 海马亚区

Abstract:

Objective ·To investigate the longitudinal changes in amygdala and hippocampal subfield volumes before and after transcranial magnetic stimulation (TMS) treatment in patients with major depressive disorder (MDD) and explore their correlation with the antidepressant and anxiolytic efficacy of TMS. Methods ·A total of 58 patients diagnosed with MDD at Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, were included in this study between January 2018 and August 2023. Clinical depressive and anxiety symptoms were assessed by using the Hamilton Depression Scale (HAMD), Montgomery-Asberg Depression Rating Scale (MADRS), and Hamilton Anxiety Scale (HAMA) at baseline and post-TMS treatment. Patients underwent a baseline magnetic resonance imaging (MRI) scan followed by TMS treatment targeting the left dorsolateral prefrontal cortex (DLPFC) at a frequency of 10 Hz, totaling 20 sessions. A follow-up MRI scan was conducted on the same day the TMS treatment concluded. Amygdala and hippocampal subfield volumes were segmented and calculated by using FreeSurfer v6.0.0 software. Longitudinal changes in the subfield volumes were analyzed with two-way analysis of variance. Controlling for age, sex, and intracranial volume, partial correlation analysis was conducted between subfield volumes and baseline clinical scores. The association between the rate of volume change in brain regions with significant volume changes and symptom improvement (reduction in HAMD, MADRS, and HAMA scores) was evaluated. Results ·Following TMS treatment, a significant increase in the volume of the right amygdala central nucleus was observed (t=-2.441, P=0.018). While the volumes of bilateral hippocampal fimbria decreased, the volumes of most hippocampal subfield and the total hippocampus increased (P<0.05). No significant correlations were found between baseline amygdala or hippocampal subfield volumes and clinical depressive and anxiety symptoms. However, only in patients who responded effectively to TMS treatment, a positive correlation was found between the volume change rate of the left hippocampal tail and reductions in anxiety symptoms (HAMA: r=0.334, P=0.044). Conclusion ·High-frequency TMS targeting the left DLPFC may induce volume increases in the right amygdala central nucleus and specific hippocampal subfields. Additionally, the volume change rate of the left hippocampal tail is associated with anti-anxiety effects in TMS responders, suggesting that high-frequency TMS targeting the left DLPFC may induce neuroplastic changes in the central nucleus of the right amygdala and key subfields of the hippocampus.

Key words: major depressive disorder, transcranial magnetic stimulation, amygdala subfield, hippocampal subfield

中图分类号:

R749.4

王思睿, 孔盖, 李惠, 钱禛颖, 崔慧茹, 唐莺莹. 经颅磁刺激治疗对抑郁症患者杏仁核及海马亚区体积的影响[J]. 上海交通大学学报（医学版）, 2025, 45(4): 434-442.

WANG Sirui, KONG Gai, LI Hui, QIAN Zhenying, CUI Huiru, TANG Yingying. Impact of transcranial magnetic stimulation therapy on the volumes of amygdala and hippocampal subfields in patients with major depressive disorder[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025, 45(4): 434-442.

图/表 7

参考文献 40

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Clinical scale	Before TMS	After TMS	T value	P value
HAMD-24	27 (12, 40)	10 (0, 27)	3.0	<0.001
MADRS	27 (16, 36)	7 (0, 26)	1.5	<0.001
HAMA	19 (9, 39)	10 (0, 27)	28.0	<0.001

Clinical scale	Before TMS	After TMS	T value	P value
HAMD-24	27 (12, 40)	10 (0, 27)	3.0	<0.001
MADRS	27 (16, 36)	7 (0, 26)	1.5	<0.001
HAMA	19 (9, 39)	10 (0, 27)	28.0	<0.001

Subfield	Time			Laterality			Time × Laterality
Subfield	F value	P value	η²	F value	P value	η²	F value	P value	η²
La	0.897	0.347	0.015	18.151	<0.001	0.242	5.533	0.022	0.088
Ba	0.352	0.556	0.006	59.562	<0.001	0.511	3.425	0.069	0.057
AB	0.075	0.785	0.001	108.26	<0.001	0.655	2.702	0.106	0.045
AAA	3.796	0.056	0.062	89.549	<0.001	0.611	1.767	0.189	0.030
Ce	4.204	0.045	0.069	44.796	<0.001	0.440	2.440	0.124	0.041
Me	2.307	0.134	0.390	29.001	<0.001	0.337	3.143	0.082	0.052
Co	0.242	0.625	0.004	102.340	<0.001	0.642	0.914	0.343	0.016
CAT	0.410	0.525	0.007	59.627	<0.001	0.511	0.281	0.598	0.005
PL	0.446	0.507	0.008	6.263	0.015	0.099	0.030	0.863	0.001
Whole amygdala	0.170	0.681	0.003	83.962	<0.001	0.596	4.825	0.032	0.078

Subfield	Time			Laterality			Time × Laterality
Subfield	F value	P value	η²	F value	P value	η²	F value	P value	η²
La	0.897	0.347	0.015	18.151	<0.001	0.242	5.533	0.022	0.088
Ba	0.352	0.556	0.006	59.562	<0.001	0.511	3.425	0.069	0.057
AB	0.075	0.785	0.001	108.26	<0.001	0.655	2.702	0.106	0.045
AAA	3.796	0.056	0.062	89.549	<0.001	0.611	1.767	0.189	0.030
Ce	4.204	0.045	0.069	44.796	<0.001	0.440	2.440	0.124	0.041
Me	2.307	0.134	0.390	29.001	<0.001	0.337	3.143	0.082	0.052
Co	0.242	0.625	0.004	102.340	<0.001	0.642	0.914	0.343	0.016
CAT	0.410	0.525	0.007	59.627	<0.001	0.511	0.281	0.598	0.005
PL	0.446	0.507	0.008	6.263	0.015	0.099	0.030	0.863	0.001
Whole amygdala	0.170	0.681	0.003	83.962	<0.001	0.596	4.825	0.032	0.078

Subfield	Time			Laterality			Time × Laterality
Subfield	F value	P value	η²	F value	P value	η²	F value	P value	η²
CA1-body	3.910	0.053	0.064	67.705	<0.001	0.543	4.673	0.035	0.067
CA1-head	0.148	0.702	0.003	86.886	<0.001	0.604	1.217	0.275	0.021
CA3-body	12.769	<0.001	0.183	82.281	<0.001	0.591	7.449	0.008	0.166
CA3-head	0.261	0.611	0.005	21.449	<0.001	0.273	1.851	0.179	0.031
CA4-body	6.293	0.015	0.099	1.844	0.180	0.031	0.002	0.968	<0.001
CA4-head	0.026	0.872	0.0005	20.487	<0.001	0.264	3.107	0.083	0.052
Fimbria	15.254	<0.001	0.211	7.824	0.007	0.121	1.837	0.181	0.031
Fissure	0.874	0.354	0.015	1.970	0.166	0.033	0.247	0.621	0.004
GC-DG-body	6.720	0.012	0.105	1.966	0.166	0.033	0.125	0.725	0.002
GC-DG-head	0.001	0.973	<0.001	25.200	<0.001	0.307	2.654	0.109	0.044
HATA	0.370	0.546	0.006	6.398	0.014	0.101	0.684	0.412	0.012
Hippocampus tail	26.765	<0.001	0.320	65.029	<0.001	0.533	0.267	0.608	0.005
ML-body	20.469	<0.001	0.264	44.278	<0.001	0.437	7.873	0.007	0.121
ML-head	0.007	0.936	<0.001	34.724	<0.001	0.379	2.142	0.149	0.036
Parasubiculum	0.064	0.801	0.001	13.377	<0.001	0.190	0.279	0.599	0.005
Presubiculum-body	6.277	0.015	0.099	18.069	<0.001	0.241	1.514	0.224	0.026
Presubiculum-head	3.017	0.083	0.052	15.834	<0.001	0.217	0.637	0.428	0.011
SUB-body	17.011	<0.001	0.230	0.010	0.921	<0.001	1.019	0.317	0.018
SUB-head	0.278	0.600	0.005	1.118	0.295	0.019	0.166	0.685	0.003
Whole hippocampus	10.728	0.002	0.158	65.042	<0.001	0.533	2.941	0.092	0.049
Whole hippocampus-body	14.750	<0.001	0.206	12.169	<0.001	0.176	3.168	0.080	0.053
Whole hippocampus-head	0.034	0.855	0.001	33.231	<0.001	0.368	1.459	0.232	0.025

经颅磁刺激治疗对抑郁症患者杏仁核及海马亚区体积的影响

Impact of transcranial magnetic stimulation therapy on the volumes of amygdala and hippocampal subfields in patients with major depressive disorder

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