Handoko Kevin, Neppach Alyssa, Snyder Ian, Karim Helmet T, Dombrovski Alexandre Y, Peciña Marta
Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania.
Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania.
Biol Psychiatry Cogn Neurosci Neuroimaging. 2025 Aug;10(8):794-803. doi: 10.1016/j.bpsc.2025.01.002. Epub 2025 Jan 11.
Acute experimental models of antidepressant placebo effects suggest that expectancies, encoded within the salience network (SN), are reinforced by sensory evidence and mood fluctuations. However, whether these dynamics extend to longer timescales remains unknown. To answer this question, we investigated how SN and default mode network (DMN) functional connectivity during the processing of antidepressant expectancies facilitates the shift from salience attribution to contextual cues in the SN to belief-induced mood responses in the DMN, both acutely and long term.
Sixty psychotropic-free patients with major depressive disorder completed an acute antidepressant placebo functional magnetic resonance imaging experiment manipulating placebo-associated expectancies and their reinforcement while assessing trial-by-trial mood improvement before entering an 8-week double-blind, randomized, placebo-controlled trial of a selective serotonin reuptake inhibitor or placebo.
Learned antidepressant expectancies predicted by a reinforcement learning model modulated SN-DMN connectivity. Acutely, greater modulation predicted higher effects of expectancy and reinforcement manipulations on reported expectancies and mood. Over 8 weeks, no significant drug effects on mood improvement were observed. However, participants who believed that they were receiving an antidepressant exhibited significantly greater mood improvement irrespective of the actual treatment received. Moreover, increased SN-DMN connectivity predicted mood improvement, especially in placebo-treated participants who believed that they received a selective serotonin reuptake inhibitor.
SN-DMN interactions may play a critical role in the evolution of antidepressant response expectancies, drug-assignment beliefs, and their effects on mood.
抗抑郁安慰剂效应的急性实验模型表明，在显著网络（SN）中编码的预期会通过感官证据和情绪波动得到强化。然而，这些动态变化是否会延伸到更长的时间尺度仍不清楚。为了回答这个问题，我们研究了在处理抗抑郁预期过程中，显著网络（SN）和默认模式网络（DMN）的功能连接如何促进从SN中对显著线索的归因到DMN中信念诱导的情绪反应的转变，包括急性和长期的转变。
60名未服用精神药物的重度抑郁症患者完成了一项急性抗抑郁安慰剂功能磁共振成像实验，该实验操纵与安慰剂相关的预期及其强化，同时在进入一项为期8周的选择性5-羟色胺再摄取抑制剂或安慰剂双盲、随机、安慰剂对照试验之前，逐试验评估情绪改善情况。
强化学习模型预测的习得性抗抑郁预期调节了SN-DMN连接。急性情况下，更大的调节预测了预期和强化操纵对报告的预期和情绪的更高影响。在8周的时间里，未观察到药物对情绪改善有显著影响。然而，无论实际接受何种治疗，相信自己正在接受抗抑郁药物治疗的参与者情绪改善更为显著。此外，SN-DMN连接增加预测了情绪改善，尤其是在相信自己接受了选择性5-羟色胺再摄取抑制剂治疗的安慰剂组参与者中。
SN-DMN相互作用可能在抗抑郁反应预期、药物分配信念及其对情绪的影响的演变中起关键作用。
