Stancil Stephani L, Yeh Hung-Wen, Brucks Morgan G, Bruce Amanda S, Voss Michaela, Abdel-Rahman Susan, Brooks William M, Martin Laura E
Divisions of Adolescent Medicine and Clinical Pharmacology, Toxicology and Therapeutic Innovation, Children's Mercy Kansas City, Kansas City, MO, United States.
Department of Pediatrics, University of Missouri-Kansas City School of Medicine, Kansas City, MO, United States.
Front Psychiatry. 2023 Jul 10;14:1161032. doi: 10.3389/fpsyt.2023.1161032. eCollection 2023.
Eating Disorders (ED) affect up to 5% of youth and are associated with reward system alterations and compulsive behaviors. Naltrexone, an opioid antagonist, is used to treat ED behaviors such as binge eating and/or purging. The presumed mechanism of action is blockade of reward activation; however, not all patients respond, and the optimal dose is unknown. Developing a tool to detect objective drug response in the brain will facilitate drug development and therapeutic optimization. This pilot study evaluated neuroimaging as a pharmacodynamic biomarker of opioid antagonism in adolescents with ED.
Youth aged 13-21 with binge/purge ED completed functional magnetic resonance imaging (fMRI) pre- and post-oral naltrexone. fMRI detected blood oxygenation-level dependent (BOLD) signal at rest and during two reward probes (monetary incentive delay, MID, and passive food view, PFV) in predefined regions of interest associated with reward and inhibitory control. Effect sizes for Δ%BOLD (post-naltrexone vs. baseline) were estimated using linear mixed effects modeling.
In 12 youth (16-21 years, 92% female), BOLD signal changes were detected following naltrexone in the nucleus accumbens during PFV (Δ%BOLD -0.08 ± 0.03; Cohen's 1.06, = 0.048) and anterior cingulate cortex during MID (Δ%BOLD 0.06 ± 0.03; Cohen's 1.25, = 0.086).
fMRI detected acute reward pathway modulation in this small sample of adolescents with binge/purge ED. If validated in future, larger trials, task-based Δ%BOLD detected by fMRI may serve as a pharmacodynamic biomarker of opioid antagonism to facilitate the development of novel therapeutics targeting the reward pathway, enable quantitative pharmacology trials, and inform drug dosing.
https://clinicaltrials.gov/ct2/show/NCT04935931, NCT#04935931.
饮食失调（ED）影响着高达5%的青少年，与奖赏系统改变和强迫行为有关。纳曲酮是一种阿片类拮抗剂，用于治疗诸如暴饮暴食和/或催吐等饮食失调行为。其假定的作用机制是阻断奖赏激活；然而，并非所有患者都有反应，且最佳剂量尚不清楚。开发一种能够检测大脑中客观药物反应的工具将有助于药物研发和治疗优化。这项试点研究评估了神经影像学作为青少年饮食失调患者阿片类拮抗作用的药效学生物标志物。
年龄在13 - 21岁、有暴饮暴食/催吐型饮食失调的青少年在口服纳曲酮前后完成功能磁共振成像（fMRI）。fMRI在与奖赏和抑制控制相关的预定义感兴趣区域检测静息状态以及两个奖赏探测任务（金钱激励延迟任务，MID，和被动食物观看任务，PFV）期间的血氧水平依赖（BOLD）信号。使用线性混合效应模型估计Δ%BOLD（纳曲酮给药后与基线相比）的效应大小。
在12名青少年（16 - 21岁，92%为女性）中，PFV期间伏隔核在纳曲酮给药后检测到BOLD信号变化（Δ%BOLD -0.08±0.03；科恩d值1.06，P = 0.048），MID期间前扣带回皮质也检测到BOLD信号变化（Δ%BOLD 0.06±0.03；科恩d值1.25，P = 0.086）。
fMRI在这一小群有暴饮暴食/催吐型饮食失调的青少年中检测到了急性奖赏通路调节。如果在未来更大规模的试验中得到验证，fMRI检测到的基于任务的Δ%BOLD可能作为阿片类拮抗作用的药效学生物标志物，以促进针对奖赏通路的新型疗法的开发，开展定量药理学试验，并为药物剂量提供依据。
https://clinicaltrials.gov/ct2/show/NCT04935931，NCT编号：04935931。
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