UMR 1253, iBrain, Université de Tours, Inserm, Tours, France.
CHU de Tours, Tours, France.
Mol Psychiatry. 2023 Sep;28(9):3900-3908. doi: 10.1038/s41380-023-02217-6. Epub 2023 Aug 17.
Nitrous oxide (NO) has recently emerged as a potential fast-acting antidepressant but the cerebral mechanisms involved in this effect remain speculative. We hypothesized that the antidepressant response to an Equimolar Mixture of Oxygen and Nitrous Oxide (EMONO) would be associated with changes in cerebral connectivity and brain tissue pulsations (BTP). Thirty participants (20 with a major depressive episode resistant to at least one antidepressant and 10 healthy controls-HC, aged 25-50, only females) were exposed to a 1-h single session of EMONO and followed for 1 week. We defined response as a reduction of at least 50% in the MADRS score 1 week after exposure. Cerebral connectivity of the Anterior Cingulate Cortex (ACC), using ROI-based resting state fMRI, and BTP, using ultrasound Tissue Pulsatility Imaging, were compared before and rapidly after exposure (as well as during exposure for BTP) among HC, non-responders and responders. We conducted analyses to compare group × time, group, and time effects. Nine (45%) depressed participants were considered responders and eleven (55%) non-responders. In responders, we observed a significant reduction in the connectivity of the subgenual ACC with the precuneus. Connectivity of the supracallosal ACC with the mid-cingulate also significantly decreased after exposure in HC and in non-responders. BTP significantly increased in the three groups between baseline and gas exposure, but the increase in BTP within the first 10 min was only significant in responders. We found that a single session of EMONO can rapidly modify the functional connectivity in the subgenual ACC-precuneus, nodes within the default mode network, in depressed participants responders to EMONO. In addition, larger increases in BTP, associated with a significant rise in cerebral blood flow, appear to promote the antidepressant response, possibly by facilitating optimal drug delivery to the brain. Our study identified potential cerebral mechanisms related to the antidepressant response of NO, as well as potential markers for treatment response with this fast-acting antidepressant.
氧化亚氮（NO）最近被认为是一种有潜力的快速抗抑郁药，但涉及这种效果的大脑机制仍在推测之中。我们假设，对等摩尔氧和氧化亚氮混合物（EMONO）的抗抑郁反应将与大脑连接和脑组织脉动（BTP）的变化相关。30 名参与者（20 名患有至少一种抗抑郁药抵抗的重度抑郁症发作，10 名健康对照者-HC，年龄 25-50 岁，仅为女性）接受了 1 小时的 EMONO 单次疗程，并在 1 周内进行了随访。我们将反应定义为暴露后 1 周内 MADRS 评分至少降低 50%。使用基于 ROI 的静息状态 fMRI 比较了前扣带皮层（ACC）的大脑连接性，使用超声组织脉动成像比较了 BTP，在 HC、无反应者和反应者中分别在暴露前、快速暴露后（以及暴露期间进行 BTP）进行了比较。我们进行了分析以比较组×时间、组和时间效应。9 名（45%）抑郁参与者被认为是反应者，11 名（55%）是非反应者。在反应者中，我们观察到亚属扣带回与楔前叶的连接明显减少。在 HC 和非反应者中，暴露后上扣带皮层与中扣带的连接也明显减少。在三组中，BTP 在基线和气体暴露之间都显著增加，但在反应者中，BTP 在最初 10 分钟内的增加仅具有统计学意义。我们发现，单次 EMONO 疗程可快速改变对 EMONO 有反应的抑郁参与者亚属扣带回-楔前叶的功能连接，这是默认模式网络中的节点。此外，BTP 的更大增加与脑血流的显著增加相关，似乎促进了抗抑郁反应，可能通过促进药物向大脑的最佳输送来实现。我们的研究确定了与 NO 抗抑郁反应相关的潜在大脑机制，以及这种快速抗抑郁药治疗反应的潜在标志物。
