Department of Psychiatry and Psychotherapy, University of Regensburg, Universitätsstrasse 84, Regensburg, 93053, Germany.
Neuropsychopharmacology. 2024 Oct;49(11):1738-1748. doi: 10.1038/s41386-024-01884-5. Epub 2024 May 31.
TSPO ligands are promising alternatives to benzodiazepines in the treatment of anxiety, as they display less pronounced side effects such as sedation, cognitive impairment, tolerance development and abuse potential. In a randomized double-blind repeated-measures study we compare a benzodiazepine (alprazolam) to a TSPO ligand (etifoxine) by assessing side effects and acquiring resting-state fMRI data from 34 healthy participants after 5 days of taking alprazolam, etifoxine or a placebo. To study the effects of the pharmacological interventions in fMRI in detail and across different scales, we combine in our study complementary analysis strategies related to whole-brain functional network connectivity, local connectivity analysis expressed in regional homogeneity, fluctuations in low-frequency BOLD amplitudes and coherency of independent resting-state networks. Participants reported considerable adverse effects such as fatigue, sleepiness and concentration impairments, related to the administration of alprazolam compared to placebo. In resting-state fMRI we found a significant decrease in functional connection density, network efficiency and a decrease in the networks rich-club coefficient related to alprazolam. While observing a general decrease in regional homogeneity in high-level brain networks in the alprazolam condition, we simultaneously could detect an increase in regional homogeneity and resting-state network coherence in low-level sensory regions. Further we found a general increase in the low-frequency compartment of the BOLD signal. In the etifoxine condition, participants did not report any significant side effects compared to the placebo, and we did not observe any corresponding modulations in our fMRI metrics. Our results are consistent with the idea that sedation globally disconnects low-level functional networks, but simultaneously increases their within-connectivity. Further, our results point towards the potential of TSPO ligands in the treatment of anxiety and depression.
TSPO 配体在治疗焦虑症方面是苯二氮䓬类药物的有前途的替代品，因为它们显示出较少的明显副作用，如镇静、认知障碍、耐受性发展和滥用潜力。在一项随机双盲重复测量研究中，我们通过评估副作用并从 34 名健康参与者中获取静息状态 fMRI 数据，比较了苯二氮䓬类药物（阿普唑仑）和 TSPO 配体（乙非他酮）的作用。为了详细研究药物干预对 fMRI 的影响，并在不同的尺度上进行研究，我们在研究中结合了与全脑功能网络连接、以局部一致性表示的局部连接分析、低频 BOLD 振幅波动和独立静息状态网络的相干性相关的互补分析策略。与安慰剂相比，服用阿普唑仑的参与者报告了相当多的不良反应，如疲劳、嗜睡和注意力障碍。在静息状态 fMRI 中，我们发现与阿普唑仑相关的功能连接密度、网络效率和网络丰富俱乐部系数显著降低。虽然在阿普唑仑状态下观察到高级脑网络的局部一致性普遍降低，但我们同时可以检测到低水平感觉区域的局部一致性和静息状态网络的增加。此外，我们还发现 BOLD 信号低频区的一般增加。在乙非他酮条件下，与安慰剂相比，参与者没有报告任何明显的副作用，我们也没有观察到 fMRI 指标的任何相应变化。我们的结果与镇静作用全局断开低水平功能网络但同时增加其内部连接的观点一致。此外，我们的结果表明 TSPO 配体在治疗焦虑和抑郁方面具有潜力。
