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

Frontiers in Psychiatry

Psychiatry

William M. Brooks¹  Amanda S. Bruce²  Susan Abdel-Rahman³  Michaela Voss³  Hung-Wen Yeh⁴  Morgan G. Brucks⁵  Laura E. Martin⁶  Stephani L. Stancil⁷ 

[1] Department of Neurology, University of Kansas Medical Center, Kansas City, KS, United States;Hoglund Biomedical Imaging Center, University of Kansas Medical Center, Kansas City, KS, United States;Department of Pediatrics, University of Kansas Medical Center School of Medicine, Kansas City, KS, United States;Center for Children’s Healthy Lifestyles and Nutrition, Kansas City, MO, United States;Department of Pediatrics, University of Missouri-Kansas City School of Medicine, Kansas City, MO, United States;Department of Pediatrics, University of Missouri-Kansas City School of Medicine, Kansas City, MO, United States;Division of Health Services and Outcomes Research, Children’s Mercy Research Institute, Kansas City, MO, United States;Department of Population Health, University of Kansas Medical Center, Kansas City, KS, United States;Department of Population Health, University of Kansas Medical Center, Kansas City, KS, United States;Hoglund Biomedical Imaging Center, University of Kansas Medical Center, Kansas City, KS, United States;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;Department of Pediatrics, University of Kansas Medical Center School of Medicine, Kansas City, KS, United States;

关键词: opioid antagonism;    eating disorders;    naltrexone;    adolescents;    pharmacodynamic biomarker;    fMRI;   

DOI  :  10.3389/fpsyt.2023.1161032

 received in 2023-02-07, accepted in 2023-05-30,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundEating 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.MethodsYouth 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.ResultsIn 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).ConclusionfMRI 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.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT04935931, NCT#04935931.

【 授权许可】

Unknown   
Copyright © 2023 Stancil, Yeh, Brucks, Bruce, Voss, Abdel-Rahman, Brooks and Martin.