Tong Xiaoyu, Fonzo Gregory A, Carlisle Nancy B, Xie Hua, Berdichevsky Yevgeny, Keller Corey J, Oathes Desmond J, Nemeroff Charles B, Zhang Yu
Department of Bioengineering, Lehigh University, Bethlehem, PA, USA.
Center for Psychedelic Research and Therapy, Department of Psychiatry and Behavioral Sciences, Dell Medical School, The University of Texas at Austin, Austin, TX, USA.
bioRxiv. 2025 Aug 28:2025.08.22.671857. doi: 10.1101/2025.08.22.671857.
Major depressive disorder (MDD) is a common and debilitating condition with limited treatment precision. While brain imaging has linked neural features to MDD diagnosis and treatment response, the underlying circuits and their early modulation by treatment remain unclear. To examine changes in functional connectivity within the first two weeks of treatment, we analyzed two independent cohorts of MDD patients receiving antidepressants or placebo. Across patients, a visual-precuneus-thalamus network showed increased functional connectivity regardless of treatment arm or clinical outcome. Placebo response involved attention and striatal systems, while drug-specific effects were localized to the amygdala, mid-cingulate, orbitofrontal cortex, and cerebellum, emerging only in a subset of medicated patients. Notably, the responses of those without drug-specific changes can be predicted with a placebo response prediction model. These early functional connectivity changes reveal common and distinct mechanisms of treatment effects, offering insights that could inform more personalized interventions for MDD.
重度抑郁症（MDD）是一种常见且使人衰弱的疾病，治疗精准度有限。虽然脑成像已将神经特征与MDD的诊断及治疗反应联系起来，但潜在的神经回路及其在治疗早期的调节情况仍不清楚。为了研究治疗前两周内功能连接的变化，我们分析了两个独立队列中接受抗抑郁药或安慰剂治疗的MDD患者。在所有患者中，一个视觉-楔前叶-丘脑网络显示出功能连接增加，无论治疗组或临床结果如何。安慰剂反应涉及注意力和纹状体系统，而药物特异性效应则定位于杏仁核、中扣带回、眶额皮质和小脑，仅在一部分接受药物治疗的患者中出现。值得注意的是，那些没有药物特异性变化的患者的反应可以用安慰剂反应预测模型来预测。这些早期功能连接变化揭示了治疗效果的共同和独特机制，为MDD更个性化的干预措施提供了思路。
