MDD作为全球致残的首要精神疾病,其诊断长期依赖主观症状评估,缺乏客观生物学标志物[1, 2]。近年来,多模态神经影像技术(如sMRI、fMRI、DWI)的发展为MDD研究开辟了新路径[2, 3]。基于静息态功能连接的机器学习模型已达到约70%的识别准确率[4],基因-影像融合研究也揭示了特定神经递质通路与脑网络异常的关联[5]。然而,现有研究多局限于静态分析,未能捕捉脑功能的动态特性,且单模态方法难以全面反映MDD的复杂病理机制。
结构-功能连接(SC-FC)耦合研究为突破传统静态和单模态分析的局限性提供了新思路[6-10]。这一研究范式通过整合脑白质结构连接(SC)与功能连接(FC)的交互关系[11-14],为理解MDD的神经病理机制提供了新视角。最新研究发现,MDD患者在关键脑网络中存在特征性的SC-FC耦合异常[9, 15],例如认网络(DMN)内部表现为耦合强度显著增强,而在前额叶皮层与边缘系统之间的连接则呈现耦合减弱,这种特异性失衡模式与患者的抑郁严重程度(HAMD评分)和认知功能障碍显著相关[9]。更为重要的是,动态功能连接(dFC)分析揭示了MDD患者脑网络动态重组的关键特征,包括脑状态转换频率较健康对照降低,以及在负性情绪相关脑状态的停留时间异常延长[16]。这些研究发现不仅证实了SC-FC特征作为MDD客观生物标志物的潜在价值,也揭示了脑网络动态重组异常可能是MDD核心临床症状产生的神经基础[17]。这一发现为理解MDD的病理机制提供了全新的视角,同时也凸显了深入研究动态SC-FC耦合模式[18]及其在MDD病理机制和临床识别中应用的重要科学意义。
然而,当前该领域研究仍面临若干关键性挑战。首先,现有的SC-FC耦合计算方法尚存在优化空间[19, 20] ,特别是在动态耦合特征的量化精度和时间分辨率方面有待提升[21] ;其次,关于SC-FC耦合的神经生理学机制尚未形成共识性认识[15] ;再者,动态SC-FC耦合特征与MDD临床症状的对应关系仍需通过大样本研究进一步验证。
当前,MDD的神经影像研究正在经历重要的范式转变。尤其是,从静态分析向动态研究转变,从单模态向多模态整合发展。在此背景下,本项目拟通过整合动态SC-FC耦合特征与机器学习算法,致力于解决以下问题:1)建立高精度、可解释的MDD智能识别模型;2)挖掘具有临床诊断价值的MDD神经影像标记物;3)阐明这些标记物背后的神经生理学基础。研究成果将为深入理解MDD的病理机制提供重要参考,并为开发客观诊断工具奠定理论基础。通过突破现有技术瓶颈,本项目有望推动MDD诊疗从症状描述向机制导向的精准医疗模式转变。
参考文献
[1] Santomauro DF, Mantilla Herrera AM, Shadid J, et al. Global prevalence and burden of depressive and anxiety disorders in 204 countries and territories in 2020 due to the COVID-19 pandemic [J]. The Lancet, 2021, 398(10312): 1700-1712.
[2] Cui L, Li S, Wang S, et al. Major depressive disorder: hypothesis, mechanism, prevention and treatment [J]. Signal Transduction and Targeted Therapy, 2024, 9(1): 30.
[3] Kang S-G, Cho S-E. Neuroimaging Biomarkers for Predicting Treatment Response and Recurrence of Major Depressive Disorder [J]. International Journal of Molecular Sciences, 2020, 21(6).
[4] Wager TD, Yamashita A, Sakai Y, et al. Generalizable brain network markers of major depressive disorder across multiple imaging sites [J]. PLOS Biology, 2020, 18(12).
[5] Anderson KM, Collins MA, Kong R, et al. Convergent molecular, cellular, and cortical neuroimaging signatures of major depressive disorder [J]. Proceedings of the National Academy of Sciences, 2020, 117(40): 25138-25149.
[6] Chu T, Si X, Song X, et al. Understanding structural-functional connectivity coupling in patients with major depressive disorder: A white matter perspective [J]. Journal of Affective Disorders, 2025, 373: 219-226.
[7] Zhang R, Shao R, Xu G, et al. Aberrant brain structural–functional connectivity coupling in euthymic bipolar disorder [J]. Human Brain Mapping, 2019, 40(12): 3452-3463.
[8] Zhang H, Cao P, Mak HKF, et al. The structural–functional-connectivity coupling of the aging brain [J]. GeroScience, 2024, 46(4): 3875-3887.
[9] Chu T, Si X, Xie H, et al. Regional Structural-Functional Connectivity Coupling in Major Depressive Disorder Is Associated With Neurotransmitter and Genetic Profiles [J]. Biological Psychiatry, 2025, 97(3): 290-301.
[10] Piao S, Chen K, Wang N, et al. Modular Level Alterations Of Structural-Functional Connectivity Coupling in Mild Cognitive Impairment Patients and Interactions with Age Effect [J]. Journal of Alzheimer's Disease, 2023, 92(4): 1439-1450.
[11] Silva PHRd, Secchinato KF, Rondinoni C, et al. Brain Structural–Functional Connectivity Relationship Underlying the Information Processing Speed [J]. Brain Connectivity, 2020, 10(3): 143-154.
[12] Fan L, Li H, Zhuo J, et al. The Human Brainnetome Atlas: A New Brain Atlas Based on Connectional Architecture [J]. Cereb Cortex, 2016, 26(8): 3508-3526.
[13] Altmayer V, Sangare A, Calligaris C, et al. Functional and structural brain connectivity in disorders of consciousness [J]. Brain Structure and Function, 2024, 10.1007/s00429-024-02839-8(
[14] Fotiadis P, Parkes L, Davis KA, et al. Structure–function coupling in macroscale human brain networks [J]. Nature Reviews Neuroscience, 2024, 25(10): 688-704.
[15] Tang L, Zhao P, Pan C, et al. Epigenetic molecular underpinnings of brain structural-functional connectivity decoupling in patients with major depressive disorder [J]. Journal of Affective Disorders, 2024, 363: 249-257.
[16] Sun S, Yan C, Qu S, et al. Resting-state dynamic functional connectivity in major depressive disorder: A systematic review [J]. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2024, 135.
[17] Zamani Esfahlani F, Faskowitz J, Slack J, et al. Local structure-function relationships in human brain networks across the lifespan [J]. Nature Communications, 2022, 13(1).
[18] Gilson M, Kouvaris NE, Deco G, et al. Network analysis of whole-brain fMRI dynamics: A new framework based on dynamic communicability [J]. Neuroimage, 2019, 201: 116007.
[19] Feng G, Wang Y, Huang W, et al. Spatial and temporal pattern of structure–function coupling of human brain connectome with development [J]. eLife, 2024, 13.
[20] Suárez LE, Markello RD, Betzel RF, et al. Linking Structure and Function in Macroscale Brain Networks [J]. Trends in Cognitive Sciences, 2020, 24(4): 302-315.
[21] Gu Z, Jamison KW, Sabuncu MR, et al. Heritability and interindividual variability of regional structure-function coupling [J]. Nature Communications, 2021, 12(1).