青少年抑郁症的皮质高阈值和低激活特征：跨年龄差异分析

摘要(中文译文)

青少年抑郁症表现出独特的神经生理特征，年龄异质性显著，尤其在重复经颅磁刺激（rTMS）期间测量的静息运动阈值（RMT）方面差异明显，临床疗效变异性大。功能性近红外光谱（fNIRS）能够评估皮层兴奋性水平；然而，探讨青少年抑郁症患者RMT与皮层激活之间关联的研究仍然有限。本研究旨在从皮层血流动力学的角度阐明潜在的神经机制，这对于进一步优化抑郁症患者的神经调控策略至关重要。我们收集了85例接受rTMS治疗的初治抑郁症患者的数据。所有患者在rTMS治疗前均完成了RMT测量、fNIRS检查和汉密尔顿抑郁量表（HAMD）评估。参与者按年龄分为三组：青少年组（n=31）、青年组（n=26）和中年组（n=28）。我们比较了三组间RMT的差异，并探讨了RMT、皮层激活（通过fNIRS反映言语流畅性任务期间前额叶氧合血红蛋白水平变化）与抑郁严重程度（通过HAMD评分评估）之间的关系。结果表明，青少年组的RMT显著高于其他年龄组（58.00 ± 11.14，< 0.001），同时伴有最低的前额叶Oxy-Hb激活水平（0.095 ± 0.06，< 0.001）。RMT与皮层激活之间呈强负相关（Spearman's rs= -0.929，< 0.001），而RMT与抑郁严重程度之间呈强正相关（= 0.837，< 0.001）。高阈值-低激活-严重症状这一独特的耦合现象在该年龄组中最为突出，理论上可能反映了更广泛情绪网络的潜在失调，尽管当前直接发现严格表明前额叶激活和运动皮层兴奋性的局部改变。青少年抑郁症中高RMT和低皮层激活的特征可作为抑郁严重程度的重要神经生物学标志物。这一发现为制定个体化、符合发育特点的神经调控策略（如优化rTMS靶点和剂量）提供了新方向，表明青少年抑郁症的干预应优先促进情绪回路的健康整合以及皮层与皮层下之间的功能协调。

Abstract

Adolescent depression exhibits distinct neurophysiological features, with marked age heterogeneity particularly in the resting motor threshold (RMT) measured during repetitive transcranial magnetic stimulation (rTMS), and substantial variability in clinical therapeutic efficacy. Functional near-infrared spectroscopy (fNIRS) enables the assessment of cortical excitability levels; however, research investigating the association between RMT and cortical activation in adolescent patients with depression remains limited. This study aims to elucidate the underlying neural mechanisms from the perspective of cortical hemodynamics, which is crucial for further optimizing neuromodulation strategies in patients with depression. We collected data from 85 treatment-naive patients with depression who underwent rTMS therapy. All patients completed RMT measurement, fNIRS examination, and Hamilton Depression Rating Scale (HAMD) assessment prior to rTMS treatment. Participants were divided into three groups according to age: the adolescents group (n=31), the young adult group (n=26), and the middle-aged group (n=28). We compared the differences in RMT among the three groups and explored the relationships between RMT, cortical activation (reflected by prefrontal oxyhemoglobin level changes during the verbal fluency task via fNIRS), and depression severity (assessed by HAMD scores). The results demonstrated that the adolescents group had a significantly higher RMT than the other age groups (58.00 ± 11.14, < 0.001), accompanied by the lowest prefrontal Oxy-Hb activation level (0.095 ± 0.06, < 0.001). A strong negative correlation was observed between RMT and cortical activation (Spearman's rs= -0.929, < 0.001), while a strong positive correlation was found between RMT and depression severity ( = 0.837, < 0.001). The distinct coupling phenomenon of high threshold-low activation-severe symptoms was most prominently manifested in this age group, which may theoretically reflect an underlying dysregulation in broader emotional networks, though the current direct findings strictly indicate localized alterations in prefrontal activation and motor cortical excitability. The characteristics of high RMT and low cortical activation in adolescent depression serve as important neurobiological markers for depression severity. This finding provides a novel direction for developing individualized, developmentally tailored neuromodulation strategies (e.g., optimization of rTMS targets and dosages), indicating that interventions for adolescent depression should prioritize promoting the healthy integration of emotional circuits and the functional coordination between the cortex and subcortex.

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