Department of Psychology, University of Haifa, Mount Carmel, 31905, Haifa, Israel.
University of Pittsburgh Department of Psychiatry, Statistics, and Biostatistics, Pittsburgh, PA, USA.
Transl Psychiatry. 2021 Sep 15;11(1):475. doi: 10.1038/s41398-021-01606-1.
Depressed patients' expectations of improvement drive placebo effects in antidepressant clinical trials, yet there is considerable heterogeneity in the magnitude of expectancy effects. The present study seeks to identify those individuals who benefit most from expectancy effects using baseline neuroimaging and cognitive measures. Older adult outpatients diagnosed with major depressive disorder (MDD) participated in a prospective, 8-week clinical trial in which expectancy was experimentally manipulated and its effects on depression outcome measured. Based on the literature, we selected a priori 12 cognitive and brain-based variables linked to depression and expectancy, together with demographic variables, and incorporated them into a combined moderator. The combined moderator was developed as a weighted combination of the individual moderators, and was used to identify individuals who benefited most from expectancy effects. The combined moderator was found to predict differential change in depression severity scores between the high- vs. low-expectancy groups with a medium-size effect (Spearman effect size: 0.28). While at the sample level no expectancy effect was found, the combined moderator divided older adults with MDD into those who did and those who did not improve as the result of expectancy manipulation, with those benefiting from the manipulation showing greater processing speed, executive function, and frontostriatal white matter tract integrity. The findings suggest that it is possible to identify a subgroup of older adult individuals with MDD for whom expectancy manipulation results in greater antidepressant treatment response, supporting a precision medicine approach. This subgroup is characterized by distinct cognitive dysfunction and neuroimaging impairments profiles.
抑郁患者对改善的期望驱动了抗抑郁药物临床试验中的安慰剂效应，但期望效应的幅度存在相当大的异质性。本研究旨在通过基线神经影像学和认知测量来确定那些从期望效应中受益最大的个体。被诊断为重度抑郁症（MDD）的老年门诊患者参加了一项前瞻性的 8 周临床试验，在该试验中，期望被实验性地操纵，并测量其对抑郁结果的影响。基于文献，我们选择了与抑郁和期望相关的 12 个认知和基于大脑的变量以及人口统计学变量，并将其纳入综合调节者中。综合调节者是通过对个体调节者进行加权组合而开发的，用于确定那些从期望效应中受益最大的个体。综合调节者被发现可以预测高期望组与低期望组之间抑郁严重程度评分的差异变化，具有中等效应（Spearman 效应量：0.28）。虽然在样本水平上没有发现期望效应，但综合调节者将 MDD 老年患者分为因期望操纵而改善和未改善的患者，那些受益于操纵的患者表现出更高的处理速度、执行功能和额-纹状体白质束完整性。研究结果表明，有可能识别出一组对期望操纵反应更大的 MDD 老年个体，支持精准医学方法。该亚组的特征是明显的认知功能障碍和神经影像学损伤特征。
