团体认知行为治疗对伴抑郁的哮喘患者的疗效机制研究

Asthma is a common psychosomatic disorder, and the coexisting rate of depression in asthma reaches 24.5%. Previous studies suggest that abnormal inflammation and neural networks have been found in both asthma and depression. However, the shared mechanisms involved in both disorder when comorbid are far from clear. Group cognitive behavior therapy (GCBT) is believed useful in improving asthma-specific emotion issues and symptoms while the therapeutic mechanism of GCBT is also poorly understood. This project recruits asthmatic patients with high homogeneity in Chinese Han population (including asthmatic patients with and without depression) and healthy controls. Clinical, immune-inflammation and neural imaging data of three groups will be collected at baseline, post-GCBT (8 weeks), and after 6 months respectively. The alterations of clinical indicators (depressive emotion, asthma control level, pulmonary function, and quality of life), immune-inflammation cytokines and neural network will be tracked at all times. With above data in hand, analysis will be done to reveal the critical regulation mechanism between immune-inflammation and neural network. Furthermore, this project aims to explore the differences of GCBT-induced changes in immune-inflammation and neural network between asthma patients with and without depression. Uncovering essential biomarkers associated with immediate and long-term outcomes of GCBT will add to our knowledge and improve the therapeutic effectiveness and quality of life.

哮喘是常见的心身疾病之一，抑郁的共患率高达24.5%，有研究发现两者均与免疫-炎症和神经网络异常有关，但两者共患的机制尚未明确。前期研究已发现团体认知行为治疗（GCBT）可以有效改善哮喘特定的情绪及症状，然而其疗效机制亦未能充分阐明。本研究率先在中国汉族人群中选择高同质性哮喘患者（伴/不伴抑郁）及相匹配的健康对照，于基线、GCBT干预8周末和6月末3个时间点，全面采集三组受试者的临床、外周免疫-炎症和神经影像学数据，动态观察哮喘患者的临床指标（抑郁情绪、哮喘控制水平、肺功能、生活质量）、外周免疫-炎症因子、神经网络的变化规律及相互关系，分析免疫-炎症因子与神经网络之间相互调控的关键机制；并进一步探讨GCBT对伴/不伴抑郁的哮喘患者外周免疫-炎症和神经网络变化规律的差异特征，寻找与GCBT近远期疗效相关的生物学标记，为提高哮喘患者的治疗效果及生存质量提供新的思路和证据。

本研究重点关注哮喘相关神经网络，同步收集高同质性哮喘患者及匹配健康对照，综合临床评估、多模态影像学、心理治疗等方法，利用多种影像学数据研究了伴/不伴抑郁哮喘患者潜在的神经生理学机制，包括白质完整性、局部脑血流量、功能连接（FC）等。并在上述基础上研究了凸显网络在哮喘控制及其抑郁情绪症状中发挥的重要作用。并进一步分析了GCBT前后脑岛FC的变化及其与症状改善之间的关系，深度挖掘了GCBT改善哮喘相关症状的疗效机制。为了验证本研究的有效性，还利用机器学习技术，采用基于数据的方法寻找GCBT干预哮喘的潜在神经影像学指标，并对GCBT干预后哮喘控制水平及情绪症状进行预测。.本研究主要结果如下：比较伴/不伴抑郁哮喘患者的脑功能特征，发现伴抑郁哮喘患者左腹侧前脑岛的FC及右侧小脑后叶局部脑血流量较不伴抑郁哮喘存在显著异常。我们对哮喘患者白质完整性及其与认知功能的分析发现哮喘患者胼胝体、扣带束等白质区域FA值显著降低，且与语义相似性测试呈显著正相关。而GCBT干预哮喘的研究结果表明GCBT能够显著改善哮喘控制水平及抑郁症状，且GCBT可能通过逆转哮喘患者异常的脑岛FC发挥其治疗作用。哮喘患者凸显网络相关研究则提示，哮喘患者凸显网络与默认网络、执行控制网络之间的连接显著增强，格兰杰因果分析证实上述网络连接具备方向性。在原计划研究基础上拓展分析的结果表明哮喘患者特定的FC能够有效地区分GCBT治疗前后的哮喘患者，且能够有效地预测治疗后的哮喘控制水平。