上海交通大学学报（医学版）

上海交通大学学报（医学版） >

2025 , Vol. 45 >Issue 4: 434 - 442

DOI: https://doi.org/10.3969/j.issn.1674-8115.2025.04.005

论著 · 临床研究

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 ,
  • 孔盖 ,
  • 李惠 ,
  • 钱禛颖 ,
  • 崔慧茹 ,
  • 唐莺莹
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  • 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
王思睿（1999—），女，硕士生；电子信箱：wangsr0305@163.com。
唐莺莹，研究员，博士；电子信箱：yytang@smhc.org.cn。

收稿日期: 2024-12-10

  录用日期: 2024-12-31

  网络出版日期: 2025-04-28

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)

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

  • WANG Sirui ,
  • KONG Gai ,
  • LI Hui ,
  • QIAN Zhenying ,
  • CUI Huiru ,
  • TANG Yingying
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  • 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
TANG Yingying, E-mail: yytang@smhc.org.cn.

Received date: 2024-12-10

  Accepted date: 2024-12-31

  Online published: 2025-04-28

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)

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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

本文引用格式

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 . DOI: 10.3969/j.issn.1674-8115.2025.04.005

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

参考文献

1 LU J, XU X F, HUANG Y Q, et al. Prevalence of depressive disorders and treatment in China: a cross-sectional epidemiological study[J]. Lancet Psychiatry, 2021, 8(11): 981-990.
2 JACOB Y, MORRIS L S, VERMA G, et al. Altered hippocampus and amygdala subregion connectome hierarchy in major depressive disorder[J]. Transl Psychiatry, 2022, 12(1): 209.
3 PLOSKI J E, VAIDYA V A. The neurocircuitry of posttraumatic stress disorder and major depression: insights into overlapping and distinct circuit dysfunction-a tribute to ron duman[J]. Biol Psychiatry, 2021, 90(2): 109-117.
4 MCKINNON M C, YUCEL K, NAZAROV A, et al. A meta-analysis examining clinical predictors of hippocampal volume in patients with major depressive disorder[J]. J Psychiatry Neurosci, 2009, 34(1): 41-54.
5 SCHMAAL L, POZZI E, HO T C, et al. ENIGMA MDD: seven years of global neuroimaging studies of major depression through worldwide data sharing[J]. Transl Psychiatry, 2020, 10(1): 172.
6 FRODL T, MEISENZAHL E, ZETZSCHE T, et al. Enlargement of the amygdala in patients with a first episode of major depression[J]. Biol Psychiatry, 2002, 51(9): 708-714.
7 KRONENBERG G, TEBARTZ VAN ELST L, REGEN F, et al. Reduced amygdala volume in newly admitted psychiatric in-patients with unipolar major depression[J]. J Psychiatr Res, 2009, 43(13): 1112-1117.
8 KIM H, HAN K M, CHOI K W, et al. Volumetric alterations in subregions of the amygdala in adults with major depressive disorder[J]. J Affect Disord, 2021, 295: 108-115.
9 CONG E Z, LI Q F, CHEN H Y, et al. Association between the volume of subregions of the amygdala and major depression with suicidal thoughts and anxiety in a Chinese cohort[J]. J Affect Disord, 2022, 312: 39-45.
10 储召松. 抑郁症患者杏仁核亚区结构磁共振成像研究[D]. 昆明: 昆明医科大学, 2021.
  CHU Z S. Structural magnetic resonance imaging study of amygdala subregions in patients with major depressive disorder[D]. Kunming: Kunming Medical University, 2021.
11 RODDY D, KELLY J R, FARRELL C, et al. Amygdala substructure volumes in major depressive disorder[J]. Neuroimage Clin, 2021, 31: 102781.
12 ZAVALIANGOS-PETROPULU A, MCCLINTOCK S M, JOSHI S H, et al. Hippocampal subfield volumes in treatment resistant depression and serial ketamine treatment[J]. Front Psychiatry, 2023, 14: 1227879.
13 WU C C, JIA L L, MU Q L, et al. Altered hippocampal subfield volumes in major depressive disorder with and without anhedonia[J]. BMC Psychiatry, 2023, 23(1): 540.
14 HAN K M, KIM A, KANG W, et al. Hippocampal subfield volumes in major depressive disorder and bipolar disorder[J]. Eur Psychiatry, 2019, 57: 70-77.
15 RODDY D W, FARRELL C, DOOLIN K, et al. The hippocampus in depression: more than the sum of its parts? Advanced hippocampal substructure segmentation in depression[J]. Biol Psychiatry, 2019, 85(6): 487-497.
16 LEFAUCHEUR J P, ALEMAN A, BAEKEN C, et al. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): an update (2014?2018)[J]. Clin Neurophysiol, 2020, 131(2): 474-528.
17 CASH R F H, ZALESKY A. Personalized and circuit-based transcranial magnetic stimulation: evidence, controversies, and opportunities[J]. Biol Psychiatry, 2024, 95(6): 510-522.
18 SYDNOR V J, CIESLAK M, DUPRAT R, et al. Cortical-subcortical structural connections support transcranial magnetic stimulation engagement of the amygdala[J]. Sci Adv, 2022, 8(25): eabn5803.
19 DALHUISEN I, ACKERMANS E, MARTENS L, et al. Longitudinal effects of rTMS on neuroplasticity in chronic treatment-resistant depression[J]. Eur Arch Psychiatry Clin Neurosci, 2021, 271(1): 39-47.
20 HAYASAKA S, NAKAMURA M, NODA Y, et al. Lateralized hippocampal volume increase following high-frequency left prefrontal repetitive transcranial magnetic stimulation in patients with major depression[J]. Psychiatry Clin Neurosci, 2017, 71(11): 747-758.
21 SEEWOO B J, RODGER J, DEMITRACK M A, et al. Neurostructural differences in adolescents with treatment-resistant depression and treatment effects of transcranial magnetic stimulation[J]. Int J Neuropsychopharmacol, 2022, 25(8): 619-630.
22 SAYGIN Z M, KLIEMANN D, IGLESIAS J E, et al. High-resolution magnetic resonance imaging reveals nuclei of the human amygdala: manual segmentation to automatic atlas[J]. Neuroimage, 2017, 155: 370-382.
23 IGLESIAS J E, AUGUSTINACK J C, NGUYEN K, et al. A computational atlas of the hippocampal formation using ex vivo, ultra-high resolution MRI: application to adaptive segmentation of in vivo MRI[J]. Neuroimage, 2015, 115: 117-137.
24 KALIN N H, SHELTON S E, DAVIDSON R J. The role of the central nucleus of the amygdala in mediating fear and anxiety in the primate[J]. J Neurosci, 2004, 24(24): 5506-5515.
25 AMARAL D G, PRICE J L, PITKANEN A, et al. The amygdala: neurobiological aspects of emotion, memory, and mental dysfunction[M]. New York: Wiley-Liss, 1992: 1-66.
26 GILPIN N W, HERMAN M A, ROBERTO M. The central amygdala as an integrative hub for anxiety and alcohol use disorders[J]. Biol Psychiatry, 2015, 77(10): 859-869.
27 TAKAMIYA A, CHUNG J K, LIANG K C, et al. Effect of electroconvulsive therapy on hippocampal and amygdala volumes: systematic review and meta-analysis[J]. Br J Psychiatry, 2018, 212(1): 19-26.
28 ENNEKING V, LEEHR E J, DANNLOWSKI U, et al. Brain structural effects of treatments for depression and biomarkers of response: a systematic review of neuroimaging studies[J]. Psychol Med, 2020, 50(2): 187-209.
29 TATU L, VUILLIER F. Structure and vascularization of the human hippocampus[J]. Front Neurol Neurosci, 2014, 34: 18-25.
30 TESEN H, WATANABE K, OKAMOTO N, et al. Volume of amygdala subregions and clinical manifestations in patients with first-episode, drug-na?ve major depression[J]. Front Hum Neurosci, 2022, 15: 780884.
31 BROWN S G, RUTLAND J W, VERMA G, et al. Structural MRI at 7T reveals amygdala nuclei and hippocampal subfield volumetric association with Major Depressive Disorder symptom severity[J]. Sci Rep, 2019, 9(1): 10166.
32 CAO B, PASSOS I C, MWANGI B, et al. Hippocampal subfield volumes in mood disorders[J]. Mol Psychiatry, 2017, 22(9): 1352-1358.
33 XU Y W, CUI D, ZHAO Y, et al. Volumetric alterations of the hippocampal subfields in major depressive disorder with and without suicidal ideation[J]. Behav Brain Res, 2023: 114733.
34 FRODL T, SCHAUB A, BANAC S, et al. Reduced hippocampal volume correlates with executive dysfunctioning in major depression[J]. J Psychiatry Neurosci, 2006, 31(5): 316-323.
35 ZHANG Y X, LIU X, YANG Y, et al. Revealing complexity: segmentation of hippocampal subfields in adolescents with major depressive disorder reveals specific links to cognitive dysfunctions[J]. Eur Psychiatry, 2024, 68(1): e5.
36 GBYL K, VIDEBECH P. Electroconvulsive therapy increases brain volume in major depression: a systematic review and meta-analysis[J]. Acta Psychiatr Scand, 2018, 138(3): 180-195.
37 MALLER J J, JEFF DASKALAKIS Z, FITZGERALD P B. Hippocampal volumetrics in depression: the importance of the posterior tail[J]. Hippocampus, 2007, 17(11): 1023-1027.
38 CHU Z S, YUAN L J, LIAN K, et al. Reduced gray matter volume of the hippocampal tail in melancholic depression: evidence from an MRI study[J]. BMC Psychiatry, 2024, 24(1): 183.
39 MALLER J J, BROADHOUSE K, RUSH A J, et al. Increased hippocampal tail volume predicts depression status and remission to anti-depressant medications in major depression[J]. Mol Psychiatry, 2018, 23(8): 1737-1744.
40 NOGOVITSYN N, MULLER M, SOUZA R, et al. Hippocampal tail volume as a predictive biomarker of antidepressant treatment outcomes in patients with major depressive disorder: a CAN-BIND report[J]. Neuropsychopharmacology, 2020, 45(2): 283-291.
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