Neurobiology of Avoidant/Restrictive Food Intake Disorder in Youth with Overweight/Obesity Versus Healthy Weight

ABSTRACT

Objective

Avoidant/restrictive food intake disorder (ARFID) occurs across the weight spectrum, however research addressing the coexistesnce of ARFID with overweight/obesity (OV/OB) is lacking. We aimed to establish co-occurrence of OV/OB and ARFID and to characterize divergent neurobiological features of ARFID by weight.

Method

Youth with full/subthreshold ARFID (12 with healthy weight [HW], 11 with OV/OB) underwent fasting brain fMRI scan while viewing food/non-food images (M age = 16.92 years, 65% female, 87% white). We compared groups on BOLD response to high-calorie foods (HCF) (vs. objects) in food cue processing regions of interest. Following fMRI scanning, we evaluated subjective hunger pre- vs. post-meal. We used a mediation model to explore the association between BMI, brain activation, and hunger.

Results

Participants with ARFID and OV/OB demonstrated significant hyperactivation in response to HCF (vs. objects) in the orbitofrontal cortex (OFC) and anterior insula compared with HW participants with ARFID. Mediation analysis yielded a significant indirect effect of group (HW vs. OV/OB) on hunger via OFC activation (effect = 18.39, SE = 11.27, 95% CI [−45.09, −3.00]), suggesting that OFC activation mediates differences in hunger between ARFID participants with HW and OV/OB.

Conclusions

Compared to youth with ARFID and HW, those with OV/OB demonstrate hyperactivation of brain areas critical for the reward value of food cues. Postprandial changes in subjective hunger depend on BMI and are mediated by OFC activation to food cues. Whether these neurobiological differences contribute to selective hyperphagia in ARFID presenting with OV/OB and represent potential treatment targets is an important area for future investigation.

KEYWORDS:

• Avoidant/restrictive food intake disorder
• ARFID
• functional magnetic resonance imaging
• fMRI
• reward
• orbitofrontal cortex

Disclosure Statement

EAL has a financial interest in OXT Therapeutics, a company developing oxytocin-based therapeutics to treat obesity and metabolic disease. EAL’s interests were reviewed and are managed by Massachusetts General Hospital and Mass General Brigham in accordance with their conflict of interest policies. Drs. Thomas, Eddy, and Becker receive royalties from Cambridge University Press for the sale of their books on ARFID.

Additional information

Funding

This work was supported by the National Institute of Mental Health [K24MH120568, R01MH108595]; Nutrition and Obesity Research Center at Harvard [P30DK04056]; Harvard Clinical and Translational Science Center [0UL1TR001102-01]; Pediatric Endocrine Society.