Sheline Yvette I, Thase Michael E, Hembree Elizabeth A, Balderston Nicholas L, Nitchie Frederick J, Batzdorf Alexandra S, Makhoul Walid, Lynch Kevin G
Center for Neuromodulation in Depression and Stress, University of Pennsylvania, Philadelphia, PA, USA.
Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
Mol Psychiatry. 2025 Mar 11. doi: 10.1038/s41380-025-02945-x.
The goals of the current study were to determine the efficacy in major depressive disorder (MDD) of a shortened, computer-augmented cognitive behavioral therapy (CCBT) protocol and to determine brain plasticity effects following CCBT. Seventy-two MDD participants were randomized to CCBT or waitlist control groups and compared to 40 healthy controls (HCs). Functional MRI data were collected for all participants and repeated for patients following CCBT (five therapist-administered manualized CBT sessions plus computer training exercises). Linear mixed-effects models evaluated changes in depression scores throughout treatment and in connectivity from pre- to post-CCBT. Linear regression models compared connectivity differences between groups (MDD vs. HC). Following CCBT, there were decreases in MADRS and BDI (ps < 0.001); there was more negative connectivity of dlPFC with sgACC and DMN with sgACC (ps < 0.002); and there was more positive connectivity of FPN with nucleus accumbens, bilateral amygdalae, bilateral hippocampi, and sgACC and of DMN with ventral and dorsal bilateral anterior insulae (ps < 0.01). There were no associations between change in MADRS and change in connectivity; however, there was an association between change in BDI and change in FPN-sgACC connectivity (p = 0.01). A shortened CBT schedule coupled with home computer exercises was associated with decreased depression symptoms and augmented PFC connectivity with multiple subcortical regions. One possible mechanism of the CCBT intervention is modulating PFC connectivity with subcortical regions, influencing top-down control of affective processes dysregulated in MDD.
本研究的目的是确定缩短版的计算机辅助认知行为疗法（CCBT）方案对重度抑郁症（MDD）的疗效，并确定CCBT后的大脑可塑性效应。72名MDD参与者被随机分为CCBT组或等待列表对照组，并与40名健康对照者（HCs）进行比较。为所有参与者收集功能磁共振成像数据，并在CCBT后对患者重复收集（五次由治疗师指导的标准化CBT疗程加计算机训练练习）。线性混合效应模型评估了整个治疗过程中抑郁评分的变化以及CCBT前后的连接性变化。线性回归模型比较了各组之间（MDD与HC）的连接性差异。CCBT后，蒙哥马利-艾森伯格抑郁评定量表（MADRS）和贝克抑郁量表（BDI）得分降低（p<0.001）；背外侧前额叶皮质（dlPFC）与膝下前扣带回（sgACC）以及默认模式网络（DMN）与sgACC之间的负连接性增加（p<0.002）；额顶叶网络（FPN）与伏隔核、双侧杏仁核、双侧海马以及sgACC之间以及DMN与双侧腹侧和背侧前脑岛之间的正连接性增加（p<0.01）。MADRS变化与连接性变化之间无关联；然而，BDI变化与FPN-sgACC连接性变化之间存在关联（p = 0.01）。缩短的CBT疗程加上家庭计算机练习与抑郁症状减轻以及前额叶皮质与多个皮质下区域的连接性增强有关。CCBT干预的一种可能机制是调节前额叶皮质与皮质下区域的连接性，影响MDD中失调的情感过程的自上而下控制。
