Clinical Summary: Differential Impact of Cholecystokinin and Ghrelin on 2-Year Avoidant/Restrictive Food Intake Disorder Symptoms
Youth with ARFID often present with low appetite, early satiety, and persistent restriction, but clinicians have little biologic guidance for understanding which symptoms are tied to appetite signaling. This study helps separate 2 potentially relevant pathways: fasting CCK tracked with lack-of-interest symptoms, while fasting ghrelin tracked with overall ARFID severity over 2 years.
Key Findings
- Greater decreases in fasting CCK from Baseline to Years 1 and 2 were associated with greater decreases in lack of interest severity scores at Years 1 and 2, respectively (Year 1: adj. R2=.41, F1, 41 =4.36, p= .043, f 2 =0.11; Year 2: adj. R2 =0.62, F1, 30 =7.00, p=.013, f 2 =0.23).
- Greater increases in fasting ghrelin from Baseline to Years 1 and 2 were associated with greater decreases in ARFID severity scores at Years 1 and 2, respectively (Year 1: adj. R2=0.35, F1, 41 =6.00, p=.02, f 2 =0.15; Year 2: adj. R2=.50, F1, 28 =6.38, p=.02, f 2 =0.23).
- Participants that met the cutoff for ARFID-lack of interest had significantly higher fasting CCK at Year 1 compared to those that did not meet the cutoff, with a large effect (η2p =.180).
- Changes in fasting ghrelin were not associated with changes in lack of interest severity scores at either follow-up (Year 1: adj. R2=0.38, F1, 42 =3.91, p=.06; Year 2: adj. R2=0.50, F1, 29 =1.56, p=.22).
- Changes in fasting CCK were not associated with changes in ARFID severity scores at either follow-up (Year 1: adj. R2=0.27, F1, 40=1.86, p=.18; Year 2: adj. R2=0.36, F1, 30 =0.39, p=.54).
In youth with full or subthreshold ARFID, CCK and ghrelin mapped onto different symptom domains over 2 years: falling CCK tracked with improvement in lack-of-interest symptoms, while rising ghrelin tracked with lower overall ARFID severity. These data support appetite hormones as clinically relevant correlates of symptom course rather than nonspecific markers of weight status alone.
Practice Implications
- When a patient’s presentation is dominated by early satiety, fullness after small amounts, or low interest in eating, consider that this symptom cluster aligned more closely with fasting CCK than with ghrelin in this study.
- When tracking overall ARFID burden over time, including medical and psychosocial consequences captured by the PARDI-severity scale, improvement was linked to increases in fasting ghrelin rather than to changes in CCK.
- Interpret biologic findings alongside age, sex, and BMI percentile rather than assuming hormone abnormalities are explained by weight status alone; the reported associations remained after accounting for these factors.
- If discussing future treatment directions with families, it is reasonable to note that the study identified CCK and ghrelin as distinct potential pharmacologic targets in ARFID, although no standardized pharmacologic treatments currently exist.
