Abstract
BACKGROUND: Avoidant/restrictive food intake disorder (ARFID) leads to faltering growth and psychosocial impairment. Three phenotypes can co-occur: fear of aversive consequences of eating (ARFID-fear phenotype), sensory sensitivity, and lack of interest in eating/food. We hypothesized that youth with ARFID, especially ARFID-fear phenotype, would show hyperactivation of fear-related regions in response to ARFID-specific fear images, compared to healthy controls (HC), and activation of these regions would positively correlate with ARFID fear severity.
METHODS: Youth (N=103: 76 ARFID, including 20 ARFID-fear phenotype; 27 HC) underwent functional MRI scanning while viewing ARFID-specific fear (e.g. vomiting, choking) versus neutral images. We compared blood-oxygen-level-dependent (BOLD) response in fear-related region of interests (ROI; e.g. amygdala, hippocampus, insula) between ARFID and ARFID-fear phenotype versus HC. We evaluated the association between brain response and ARFID fear severity in ARFID-fear phenotype.
RESULTS: Across individuals, there was a robust bilateral amygdala response to ARFID-specific fear versus neutral images. Compared to HC, ARFID-fear phenotype showed a greater insula response to ARFID-specific fear versus neutral images (p=0.049). There were no other group differences and no significant relationships between BOLD response and ARFID fear severity in ARFID-fear phenotype.
CONCLUSIONS: ARFID-specific fear images elicit amygdala responses across individuals, with greater activation in the insula only in ARFID-fear phenotype versus HC. These findings validate the ARFID-specific fear paradigm and highlight the intriguing possibility that, in the ARFID-fear phenotype, universally feared experiences such as choking and vomiting serve as the unconditioned stimulus in developing ARFID and may partially be mediated by the insular cortex.