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.

在抗抑郁药临床试验中，抑郁患者对改善的期望推动安慰剂效应，但预期效应的大小存在相当大的异质性。本研究旨在确定那些使用基线神经影像学和认知测量从预期效应中受益最多的个体。被诊断患有重度抑郁症 (MDD) 的老年门诊患者参加了一项为期 8 周的前瞻性临床试验，在该试验中通过实验操纵预期并测量其对抑郁结果的影响。根据文献，我们先验地选择了 12 个与抑郁和预期相关的认知和基于大脑的变量，以及人口统计变量，并将它们合并到一个组合调节器中。组合主持人是作为单个主持人的加权组合开发的，并用于识别从预期效果中受益最多的个人。发现组合调节剂可预测高预期组与低预期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预期效应，但联合调节者将患有 MDD 的老年人分为因预期操纵而改善的和未改善的，受益于操纵的人表现出更快的处理速度、执行功能、和额纹状体白质束的完整性。研究结果表明，有可能确定一个患有 MDD 的老年个体亚组，对他们来说，预期操作会导致更大的抗抑郁治疗反应，从而支持精准医学方法。