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The Journal of Clinical Psychiatry

Original Research May 20, 2026

Differential Impact of Cholecystokinin and Ghrelin on 2-Year Avoidant/Restrictive Food Intake Disorder Symptoms

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J Clin Psychiatry 2026;87(2):25m16046

Abstract

Objective: Individuals with avoidant/restrictive food intake disorder (ARFID) commonly endorse lacking interest in eating/food, difficulties recognizing hunger, and early satiation. Cholecystokinin (CCK) and ghrelin may be important biologic mechanisms in ARFID given their role in appetite signaling. We investigated whether youth with ARFID-lack of interest had greater CCK and lower ghrelin levels compared to youth without this presentation across timepoints and whether greater reductions in CCK and increases in ghrelin were associated with ARFID symptom improvement over a two-year period.

Methods: One hundred youth (49% female, mean [SD] age=15.87 [3.89] years, mean [SD] body mass index percentile=37.71 [35.16]) recruited from a single-center clinic and surrounding community, initially meeting DSM-5 criteria for full/subthreshold ARFID completed the Pica, ARFID, and Rumination Disorder Interview at baseline and follow-up over two years (July 2016–September 2022) to determine ARFID diagnosis, presentation type, and severity scores. We obtained fasting plasma levels of CCK and ghrelin at each timepoint.

Results: Youth with ARFID-lack of interest had higher CCK than those without this presentation, though there were no differences in fasting ghrelin. Greater decreases in CCK from Baseline to Years 1 and 2 were associated with decreases in lack of interest severity at Years 1 and 2, whereas greater increases in ghrelin from Baseline to Years 1 and 2 were associated with decreases in ARFID severity at Years 1 and 2.

Conclusion: In the first longitudinal study of neuroendocrine abnormalities in individuals with ARFID, we found that decreases in CCK and increases in ghrelin were associated with improvements in ARFID symptomology.

J Clin Psychiatry 2026;87(2):25m16046

Author affiliations are listed at the end of this article.

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