Ketamine has shown promise in rapidly improving symptoms of depression and most notably treatment-resistant depression (TRD). However, given the heterogeneity of TRD, biobehavioral markers of treatment response are necessary for the personalized prescription of intravenous ketamine. Heterogeneity in depression can be manifested in discrete patterns of functional connectivity (FC) in default mode, ventral affective, and cognitive control networks. This study employed a data-driven approach to parse FC during positive mood processing to characterize subgroups of patients with TRD prior to infusion and determine whether these connectivity-based subgroups could predict subsequent antidepressant response to ketamine compared to saline infusion. 152 adult patients with TRD completed a baseline assessment of FC during positive mood processing and were randomly assigned to either ketamine or saline infusion. The assessment utilized Subgroup-Group Iterative Multiple Model Estimation to recover directed connectivity maps and applied Walktrap algorithm to determine data-driven subgroups. Depression severity was assessed pre- and 24-hr postinfusion. Two connectivity-based subgroups were identified: Subgroup A (n = 110) and Subgroup B (n = 42). We observed that treatment response was moderated by an infusion type by subgroup interaction (p = .040). For patients receiving ketamine, subgroup did not predict treatment response (β = -.326, p = .499). However, subgroup predicted response for saline patients. Subgroup B individuals, relative to A, were more likely to be saline responders at 24-hr postinfusion (β = -2.146, p = .007). Thus, while ketamine improved depressive symptoms uniformly across both subgroups, this heterogeneity was a predictor of placebo response. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

中文翻译：

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积极情绪诱导期间的功能连接亚型：预测氯胺酮治疗难治性抑郁症的随机对照试验中的临床反应。


氯胺酮在快速改善抑郁症症状，特别是难治性抑郁症 (TRD) 方面显示出良好的前景。然而，考虑到 TRD 的异质性，治疗反应的生物行为标志物对于静脉注射氯胺酮的个性化处方是必要的。抑郁症的异质性可以表现为默认模式、腹侧情感和认知控制网络中功能连接（FC）的离散模式。这项研究采用数据驱动的方法在积极情绪处理过程中解析 FC，以在输注前描述 TRD 患者亚组的特征，并确定这些基于连接的亚组是否可以预测与盐水输注相比随后对氯胺酮的抗抑郁反应。 152 名 TRD 成年患者在积极情绪处理过程中完成了 FC 基线评估，并被随机分配接受氯胺酮或盐水输注。该评估利用子组-组迭代多模型估计来恢复有向连接图，并应用 Walktrap 算法来确定数据驱动的子组。在输注前和输注后24小时评估抑郁严重程度。确定了两个基于连通性的亚组：亚组 A (n = 110) 和亚组 B (n = 42)。我们观察到治疗反应通过亚组相互作用受到输注类型的调节 (p = .040)。对于接受氯胺酮的患者，亚组不能预测治疗反应（β = -.326，p = .499）。然而，亚组预测了盐水患者的反应。相对于 A 亚组，B 亚组个体在输注后 24 小时更有可能出现盐水反应（β = -2.146，p = .007）。因此，虽然氯胺酮在两个亚组中均能改善抑郁症状，但这种异质性是安慰剂反应的预测因子。 （PsycInfo 数据库记录 (c) 2024 APA，保留所有权利）。