442 Exposure therapy for anorexia nervosa: Targeting weight gain anxiety as a treatment mechanism

Objectives/Goals: Treatments for adults with anorexia nervosa (AN) are inadequate, with no FDA-approved medications and only 30% achieving remission in psychotherapy trials. This ongoing KL2-funded pilot study evaluates Exposure Therapy for AN (Exp-AN), which targets anxiety about weight gain – a key mechanism maintaining AN. Methods/Study Population: Preliminary results (target N=16) include six adults (100% female, 83% White, 17% Black, ages 18–24, mean=20.5 years) with AN or atypical AN who have completed Exp-AN, a standardized 20-session outpatient therapy delivered in both in-person and virtual formats over 20 weeks. Exp-AN combines in vivo (e.g., stepping on a scale) and imaginal (e.g., listening to scripts about catastrophic weight gain) exposures to challenge anxious beliefs and enhance tolerance related to weight gain. Measures assessing treatment acceptability, AN symptomatology, and anxiety about weight gain were administered at baseline and end-of-treatment. Mean scores and effect sizes were calculated and compared to predetermined benchmarks to evaluate preliminary signals of acceptability, efficacy, and target engagement. Results/Anticipated Results: On two acceptability items (scale: 1=“not at all” to 7=“extremely”), participants rated Exp-AN as 5.8/7 on helpfulness and 6.3/7 on logic, meeting our 5/7 benchmark. All within-subjects effect sizes (Cohen’s d from paired samples t-tests) met our benchmark for large effects (d≥0.8), indicating improvements from baseline to end-of-treatment in: AN symptomatology (d=1.37), anxiety ratings about weight gain (d=1.22), anxious beliefs about weight gain (d =1.06), and tolerance of weight gain (d=1.40). Pearson’s correlations exploring whether changes in weight gain anxiety were associated with AN symptom improvement met our benchmark (r≥0.5) for anxiety ratings (r=0.55) and anxious beliefs (r=0.65), but not tolerance of weight gain (r=0.18). Discussion/Significance of Impact: Results support Exp-AN’s acceptability and preliminary efficacy. Reductions in weight gain anxiety correlated with symptom improvement, suggesting target engagement. By targeting specific mechanisms, this work advances precision medicine and treatment optimization. Findings warrant a fully powered randomized controlled trial.