# Neurobiological Underpinnings of Avoidant/Restrictive Food Intake Disorder in Adults

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $39,303

## Abstract

ABSTRACT
 Avoidant/restrictive food intake disorder (ARFID) affects 1-4% of adults and is associated with weight
loss, nutritional deficiencies, suicidality, and psychosocial impairment. ARFID is heterogeneous, with poor
intake characterized by extreme fear of choking, vomiting, or allergic reaction (ARFID-fear of aversive
consequences); lack of interest in eating (ARFID-lack of interest); and/or extreme food selectivity (ARFID-
sensory sensitivity). Very little is known about the pathophysiology of this serious mental health condition,
particularly among adults whose illness has followed a chronic course. Our study will leverage unique and
complementary contributions of a multidisciplinary team with expertise in clinical psychology,
neuroendocrinology, and neuroscience to investigate the pathophysiology of ARFID in adults. We will
establish a cohort of adults age 18-45 years with ARFID (n=150) and healthy controls (n=50) matched for
sex and age to investigate how, across units of analysis, RDoC constructs contribute to ARFID phenotypes.
First, we hypothesize that Negative Valence (acute threat/fear) hyperactivity (hormones: cortisol in response
to a meal; circuitry: amygdala, anterior cingulate cortex, and orbitofrontal cortex activation during a validated
food-cue paradigm) will correlate with severity of ARFID-fear of aversive consequences. Second, we
hypothesize that Arousal/Regulatory (homeostasis) dysfunction (hormones: CKK, ghrelin in response to a
meal; circuitry: hypothalamus activation during a validated food-cue paradigm) will correlate with severity of
ARFID-lack of interest. Third, we hypothesize that Cognitive Systems (somatosensory perception) over-
sensitivity (hormones: oxytocin in response to a meal; circuitry: activation in the somatosensory cortex and
supplemental motor cortex during a validated food-cue paradigm) will correlate with severity of ARFID-
sensory sensitivity. We also expect each ARFID phenotype to have greater dysfunction in the corresponding
RDoC construct than controls. This study will be innovative and unique by providing an empirical investigation
of an understudied clinical presentation and by investigating—for the first time—ARFID pathophysiology in
adults. In sum, conceptualizing ARFID within an RDoC framework that integrates both endocrine signaling
and neural circuitry has strong potential to advance precision medicine in ARFID by identifying mechanistic
targets that could be intervened upon (e.g., through neuromodulation and/or hormone agonists/antagonists)
to reduce the burden of ARFID across the lifespan.

## Key facts

- **NIH application ID:** 11094272
- **Project number:** 3R01MH128246-03S1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** LAURA McGrath HOLSEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $39,303
- **Award type:** 3
- **Project period:** 2022-09-01 → 2025-04-23

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11094272

## Citation

> US National Institutes of Health, RePORTER application 11094272, Neurobiological Underpinnings of Avoidant/Restrictive Food Intake Disorder in Adults (3R01MH128246-03S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11094272. Licensed CC0.

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