Potential biomarker of brain response to opioid antagonism in adolescents with eating disorders: a pilot study.

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 d −1.06, p = 0.048) and anterior cingulate cortex during MID (Δ%BOLD 0.06 ± 0.03; Cohen’s d 1.25, p = 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.

进食障碍（ED）影响多达5%的青少年，并且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/或催吐等进食障碍行为。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，且最佳剂量未知。开发一种检测大脑中药物客观反应的工具将促进药物研发和治疗优化。这项初步研究评估了神经影像学作为进食障碍青少年阿片类拮抗作用的药效学生物标志物。 患有暴饮暴食/催吐型进食障碍的13 - 21岁青少年在口服纳曲酮前后完成了功能性磁共振成像（fMRI）。fMRI检测了在静息状态以及在两个奖赏探测任务（金钱激励延迟，MID，和被动观看食物，PFV）期间，与奖赏和抑制控制相关的预定感兴趣区域的血氧水平依赖（BOLD）信号。使用线性混合效应模型估计了Δ%BOLD（纳曲酮后与基线相比）的效应量。 在12名青少年（16 - 21岁，92%为女性）中，在PFV期间伏隔核以及在MID期间前扣带回皮质检测到纳曲酮后的BOLD信号变化。在PFV期间伏隔核的Δ%BOLD为 -0.08 ± 0.03；科恩d值为 -1.06，p = 0.048；在MID期间前扣带回皮质的Δ%BOLD为0.06 ± 0.03；科恩d值为1.25，p = 0.086。 fMRI在这一小样本的暴饮暴食/催吐型进食障碍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，实现定量药理学试验，并为药物剂量提供依据。 https://clinicaltrials.gov/ct2/show/NCT04935931，NCT#04935931