Choi Kang-Min, Lee Taegyeong, Lee Seung-Hwan, Im Chang-Hwan
Department of Electronic Engineering, Hanyang University, Seoul 04763, Republic of Korea.
Clinical Emotion and Cognition Research Laboratory, Inje University, Goyang, Gyeonggi-do 10380, Republic of Korea.
Int J Neuropsychopharmacol. 2025 Jul 23;28(7). doi: 10.1093/ijnp/pyaf042.
Heterogeneous pathophysiological characteristics in patients with major depressive disorder (MDD) lead to individually differentiated sensitivities to antidepressants. Based on the hypothesis that gamma-band dynamic fluctuations in cortical functional connectivity (FC) in response to salient stimuli are linked to pathophysiological characteristics, we conducted a classification analysis for antidepressant responsiveness prediction.
Biosignals and psychological measures were acquired from 47 patients with MDD prior to treatment. After 8 weeks of antidepressant therapy, patients were divided into non-remitted MDD (nrMDD; aged 42.55 ± 11.52 years; n = 20) and remitted MDD (rMDD; aged 47.22 ± 11.59 years; n = 27) groups based on their depressive symptom reduction. Electroencephalography (EEG) signals were acquired during the duration-variant auditory mismatch negativity paradigm. From the deviant condition, gamma-band weighted phase-lag index-based dynamic fluctuations were evaluated using a template generated from 21 demography-matched healthy control (aged 43.81 ± 14.10 years) data.
Using these dynamic functional connectivity (dFC) features, a machine learning-based classification analysis was performed for nrMDD and rMDD. Using leave-one-out cross-validation, the linear discriminant analysis classifier achieved the best accuracy (82.98%) for classifying nrMDD and rMDD. Further simple effect analyses identified three core dFC features for nrMDD: (i) relatively intact time-dependent FC between the left frontal and right temporal regions; (ii) disrupted right frontoparietal FC; and (iii) disrupted left fronto-temporal FC. These dFC features commonly exhibit transient hyperconnections in patients with nrMDD.
We demonstrated that gamma-band dFC responses to salient stimuli could serve as potential biomarkers for antidepressant responsiveness prediction in patients with MDD.
重度抑郁症(MDD)患者的病理生理特征存在异质性,导致对抗抑郁药的敏感性存在个体差异。基于这样的假设,即对显著刺激的皮质功能连接(FC)中的γ波段动态波动与病理生理特征相关,我们进行了一项分类分析以预测抗抑郁药反应性。
在治疗前从47例MDD患者获取生物信号和心理测量数据。经过8周的抗抑郁治疗后,根据抑郁症状减轻情况将患者分为未缓解的MDD(nrMDD;年龄42.55±11.52岁;n = 20)和缓解的MDD(rMDD;年龄47.22±11.59岁;n = 27)组。在时长可变的听觉失配负波范式期间采集脑电图(EEG)信号。从偏差条件下,使用从21名人口统计学匹配的健康对照(年龄43.81±14.10岁)数据生成的模板评估基于γ波段加权相位滞后指数的动态波动。
使用这些动态功能连接(dFC)特征,对nrMDD和rMDD进行了基于机器学习的分类分析。使用留一法交叉验证,线性判别分析分类器在区分nrMDD和rMDD时达到了最佳准确率(82.98%)。进一步的简单效应分析确定了nrMDD的三个核心dFC特征:(i)左额叶和右颞叶区域之间相对完整的时间依赖性FC;(ii)右侧额顶叶FC中断;以及(iii)左侧额颞叶FC中断。这些dFC特征在nrMDD患者中通常表现为短暂的过度连接。
我们证明,对显著刺激的γ波段dFC反应可作为MDD患者抗抑郁药反应性预测的潜在生物标志物。