PII-006 - EARLY PHARMACODYNAMIC BIOMARKER DEVELOPMENT IN ADOLESCENTS WITH EATING DISORDERS.

S. Stancil¹, M. Brucks², H. Yeh¹, M. Voss¹, A. Bruce², S. Abdel-Rahman¹, L. Martin²; ¹Children's Mercy Kansas City, Kansas City, MO, USA, ²University of Kansas Medical Center, Kansas City, KS, USA.

Background: Eating Disorders (ED) affect up to 5% of youth & are associated with brain reward system alterations and compulsive behaviors. Naltrexone (NTX), an opioid antagonist, reduces these compulsive behaviors in some, but not all. Developing a tool to detect objective drug response in the brain will facilitate a precision therapeutics approach. This study evaluates fMRI as a pharmacodynamic biomarker of opioid antagonism in adolescents with ED.

Methods: Youth aged 13-21 y with ED completed baseline functional magnetic resonance imaging (fMRI) before NTX and an fMRI 2 hours post-NTX (pre/post design). fMRI detected blood oxygenation-level dependent (BOLD) changes at rest and during two reward probes (monetary incentive delay, MID, & passive food view, PFV) in predefined regions of interest associated with inhibitory control (dorsal anterior cingulate cortex-dACC, dorsolateral pre-frontal cortex, dlPFC) and reward (nucleus accumbens-NAc). Effect sizes for %BOLD (post-NTX vs. baseline) were estimated from Bayesian-weighted linear mixed effects modeling.

Results: In 12 youth, aged 17± 2.1 yr (16-21 yr), 83% female, 8% gender diverse, fMRI detected %BOLD in the dACC during MID (%BOLD 0.06±0.10; Cohen’s d 0.61) and the NAc during PFV (%BOLD -0.08±0.06; Cohen’s d -1.33). Post-NTX, functional connectivity between dlPFC and NAc decreased (posterior meanΔ Fisher's z -0.09±0.06, Cohen's d -1.57).

Conclusion: Task-based fMRI detected acute reward pathway modulation by opioid antagonism in youth with ED. Post-NTX, increased activation in the dACC suggests improved inhibitory control and decreased activation in the NAc suggests reduced reward response. Further work is needed to validate fMRI as a pharmacodynamic biomarker for pediatric neuropsychopharmacology drug development and repurposing.