Trajectory of ghrelin and PYY around a test meal in males and females with avoidant/restrictive food intake disorder versus healthy controls.

Disruptions in appetite-regulating hormones may contribute to the development and/or maintenance of avoidant/restrictive food intake disorder (ARFID). No study has previously assessed fasting levels of orexigenic ghrelin or anorexigenic peptide YY (PYY), nor their trajectory in response to food intake among youth with ARFID across the weight spectrum. We measured fasting and postprandial (30, 60, 120 minutes post-meal) levels of ghrelin and PYY among 127 males and females with full and subthreshold ARFID (n = 95) and healthy controls (HC; n = 32). We used latent growth curve analyses to examine differences in the trajectories of ghrelin and PYY between ARFID and HC. Fasting levels of ghrelin did not differ in ARFID compared to HC. Among ARFID, ghrelin levels declined more gradually than among HC in the first hour post meal (p =.005), but continued to decline between 60 and 120 minutes post meal, whereas HC plateaued (p =.005). Fasting and PYY trajectory did not differ by group. Findings did not change after adjusting for BMI percentile (M(SD)ARFID = 37(35); M(SD)HC = 53(26); p =.006) or calories consumed during the test meal (M(SD)ARFID = 294(118); M(SD)HC = 384 (48); p <.001). These data highlight a distinct trajectory of ghrelin following a test meal in youth with ARFID. Future research should examine ghrelin dysfunction as an etiological or maintenance factor of ARFID.

Medical Comorbidities, Nutritional Markers, and Cardiovascular Risk Markers in Youth With ARFID.

OBJECTIVE: Avoidant/restrictive food intake disorder (ARFID) is common among populations with nutrition-related medical conditions. Less is known about the medical comorbidity/complication frequencies in youth with ARFID. We evaluated the medical comorbidities and metabolic/nutritional markers among female and male youth with full/subthreshold ARFID across the weight spectrum compared with healthy controls (HC). METHOD: In youth with full/subthreshold ARFID (n = 100; 49% female) and HC (n = 58; 78% female), we assessed self-reported medical comorbidities via clinician interview and explored abnormalities in metabolic (lipid panel and high-sensitive C-reactive protein [hs-CRP]) and nutritional (25[OH] vitamin D, vitamin B12, and folate) markers. RESULTS: Youth with ARFID, compared with HC, were over 10 times as likely to have self-reported gastrointestinal conditions (37% vs. 3%; OR = 21.2; 95% CI = 6.2-112.1) and over two times as likely to have self-reported immune-mediated conditions (42% vs. 24%; OR = 2.3; 95% CI = 1.1-4.9). ARFID, compared with HC, had a four to five times higher frequency of elevated triglycerides (28% vs. 12%; OR = 4.0; 95% CI = 1.7-10.5) and hs-CRP (17% vs. 4%; OR = 5.0; 95% CI = 1.4-27.0) levels. DISCUSSION: Self-reported gastrointestinal and certain immune comorbidities were common in ARFID, suggestive of possible bidirectional risk/maintenance factors. Elevated cardiovascular risk markers in ARFID may be a consequence of limited dietary variety marked by high carbohydrate and sugar intake.

Prospective 2-Year Course and Predictors of Outcome in Avoidant/Restrictive Food Intake Disorder.

OBJECTIVE: To evaluate the 2-year course and outcomes of full and subthreshold avoidant/restrictive food intake disorder (ARFID) in youth aged 9 to 23 at baseline using a prospective longitudinal design to characterize the remission and persistence of ARFID, evaluate diagnostic crossover, and identify predictors of outcome. Greater severity in each ARFID profile-sensory sensitivity, fear of aversive consequences, and lack of interest-was hypothesized to predict greater likelihood of illness persistence, controlling for age, sex, body mass index percentile, ARFID treatment status, and baseline diagnosis. METHOD: Participants (N = 100; age range, 9-23 years; 49% female; 91% White) were followed over 2 years. The Pica, ARFID, and Rumination Disorder Interview was used across 3 time points (baseline, year 1, year 2) to measure the severity of each ARFID profile and evaluate illness persistence or remission, and the Eating Disorder Assessment for DSM-5 was used to evaluate diagnostic crossover. RESULTS: Across the 2-year follow-up period, half the participants persisted with their original diagnosis, and 3% of participants experienced a diagnostic shift to anorexia nervosa. Greater severity in the sensory sensitivity and lack of interest profiles was associated with higher likelihood of ARFID persistence at year 1 only; greater severity in the fear of aversive consequences profile was associated with higher likelihood of ARFID remission at year 2 only. CONCLUSION: Findings underscore the distinctiveness of ARFID from other eating disorders and emphasize its persistence over 2 years. Results also highlight the predictive validity and prognostic value of ARFID profiles (ie, sensory sensitivity, fear of aversive consequences, lack of interest).

Low bone mineral density is found in low weight female youth with avoidant/restrictive food intake disorder and associated with higher PYY levels.

BACKGROUND: Avoidant/restrictive food intake disorder (ARFID) is a restrictive eating disorder commonly associated with medical complications of undernutrition and low weight. In adolescence, a critical time for bone accrual, the impact of ARFID on bone health is uncertain. We aimed to study bone health in low-weight females with ARFID, as well as the association between peptide YY (PYY), an anorexigenic hormone with a role in regulation of bone metabolism, and bone mineral density (BMD) in these individuals. We hypothesized that BMD would be lower in low-weight females with ARFID than healthy controls (HC), and that PYY levels would be negatively associated with BMD. METHODS: We performed a cross-sectional study in 14 adolescent low-weight females with ARFID and 20 HC 10-23 years old. We assessed BMD (total body, total body less head and lumbar spine) using dual x-ray absorptiometry (DXA) and assessed fasting total PYY concentration in blood. RESULTS: Total body BMD Z-scores were significantly lower in ARFID than in HC (- 1.41 ± 0.28 vs. - 0.50 ± 0.25, p = 0.021). Mean PYY levels trended higher in ARFID vs. HC (98.18 ± 13.55 pg/ml vs. 71.40 ± 5.61 pg/ml, p = 0.055). In multivariate analysis within the ARFID group, PYY was negatively associated with lumbar BMD adjusted for age (ß = -0.481, p = 0.032). CONCLUSION: Our findings suggest that female adolescents with low-weight ARFID may have lower BMD than healthy controls and that higher PYY levels may be associated with lower BMD at some, but not all, sites in ARFID. Further research with larger samples will be important to investigate whether high PYY drives bone loss in ARFID.

Avoidant/restrictive food Intake disorder (ARFID) is a condition characterized by lack of interest in eating/food, sensory sensitivity and/or fear of aversive consequences of eating. It is associated with low weight and undernutrition, which can lead to medical complications. Specifically, low weight in patients with ARFID raises concerns of impaired bone health. In this study, we compared bone mineral density (BMD), a measure of bone health, in 14 low-weight females with ARFID and 20 healthy females 10­23 years old. We also examined the association between BMD and peptide YY (PYY), a hormone that induces satiety and inhibits bone formation. A strong negative association between bone health and PYY was previously reported in females with anorexia nervosa. Thus, we hypothesized a similar association in low weight females with ARFID. We found that BMD may be lower in low-weight females with ARFID than in healthy females and that higher PYY levels are associated with lower BMD at some but not all sites. We concluded that bone health may be a concern in low-weight females with ARFID. This finding is important as low BMD raises concerns for increased fracture risk, which in turn could have a detrimental effect on quality of life.

Preliminary validation of the pica, ARFID and rumination disorder interview ARFID questionnaire (PARDI-AR-Q).

BACKGROUND: The Pica, ARFID, and Rumination Disorder Interview (PARDI) is a structured interview that can be used to determine diagnosis, presenting characteristics, and severity across three disorders, including avoidant/restrictive food intake disorder (ARFID). The purpose of this study was to evaluate the psychometric properties of a questionnaire focused specifically on ARFID (PARDI-AR-Q), which has the potential to provide related information with less participant burden. METHODS: Adolescents and adults (n = 71, ages 14-40 years) with ARFID (n = 42) and healthy control participants (HC, n = 29) completed the PARDI-AR-Q and other measures. A subset of the ARFID group (n = 27) also completed the PARDI interview. RESULTS: An exploratory factor analysis of proposed subscale items identified three factors corresponding to the ARFID phenotypes of avoidance based on the sensory characteristics of food, lack of interest in eating or food, and concern about aversive consequences of eating. Further analyses supported the internal consistency and convergent validity of the PARDI-AR-Q subscales, and subscale ratings on the questionnaire showed large and significant correlations (all p-values < 0.001; r's ranging from 0.48 to 0.77) with the corresponding subscales on the interview. The ARFID group scored significantly higher than HC on all subscales. Furthermore, 90% of the ARFID group scored positive on the PARDI-AR-Q diagnostic algorithm while 93% of the HC scored negative. CONCLUSIONS: Though replication in larger and more diverse samples is needed, findings provide early support for the validity of the PARDI-AR-Q as a self-report measure for possible ARFID in clinical or research settings.

Differential comorbidity profiles in avoidant/restrictive food intake disorder and anorexia nervosa: Does age play a role?

OBJECTIVE: Research comparing psychiatric comorbidities between individuals with avoidant/restrictive food intake disorder (ARFID) and anorexia nervosa (AN) is limited. ARFID often develops in childhood, whereas AN typically develops in adolescence or young adulthood. Understanding how age may impact differential psychological comorbidity profiles is important to inform etiological conceptualization, differential diagnosis, and treatment planning. We aimed to compare the lifetime frequency of psychiatric comorbidities and suicidality between females with ARFID (n = 51) and AN (n = 40), investigating the role of age as a covariate. METHOD: We used structured interviews to assess the comparative frequency of psychiatric comorbidities/suicidality. RESULTS: When age was omitted from analyses, females with ARFID had a lower frequency of depressive disorders and suicidality compared to AN. Adjusting for age, only suicidality differed between groups. DISCUSSION: This is the first study to compare comorbidities in a similar number of individuals with ARFID and AN, and a structured clinical interview to confer ARFID and comorbidities, covarying for age, and the first to compare suicidality. Although suicidality is at least three times less common in ARFID than AN, observed differences in other psychiatric comorbidities may reflect ARFID's relatively younger age of presentation compared to AN. PUBLIC SIGNIFICANCE: Our results highlight that, with the exception of suicidality, which was three times less common in ARFID than AN irrespective of age, observed differences in psychiatric comorbidities in clinical practice may reflect ARFID's younger age at clinical presentation compared to AN.

Elevated Fasting Satiety-Promoting Cholecystokinin (CCK) in Avoidant/Restrictive Food Intake Disorder Compared to Healthy Controls.

Objective: Avoidant/restrictive food intake disorder (ARFID) is characterized by food avoidance or dietary restriction not primarily motivated by body weight/shape concerns. Individuals with ARFID can report early satiation, post-prandial fullness, and high intermeal satiety, but whether these symptoms are related to differences in the biology underlying appetite regulation is unknown. In male and female children and adolescents, we hypothesized that fasting levels of cholecystokinin (CCK), a satiety hormone, would be elevated in participants with ARFID (full or subthreshold) versus healthy controls (HCs). Within the ARFID group, we also explored the relations of CCK with weight status, subjective appetite ratings, and ARFID severity and phenotypes.Methods: A total of 125 participants (83 with full/subthreshold ARFID (per DSM-5) and 42 HCs, aged 10.2-23.7 years; 61% female; July 2014-December 2019) underwent fasting blood draws for CCK, completed self-report measures assessing subjective state and trait appetite ratings, and completed a semistructured interview assessing ARFID severity.Results: Fasting CCK was higher in those with full/subthreshold ARFID versus HCs with a large effect (F1 = 25.0, P < .001, ηp2 = 0.17), controlling for age, sex, and body mass index (BMI) percentile. Within the ARFID group, CCK was not significantly related to BMI percentile, subjective appetite ratings, or ARFID characteristic measures.Conclusions: CCK may contribute to etiology and/or maintenance of ARFID, as children and adolescents with heterogeneous presentations of avoidant/restrictive eating appear to show elevated fasting levels compared to healthy youth. Further research is needed to understand relations between CCK and appetite, weight, and eating behavior in ARFID.

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

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.

A Moving Target: How We Define Avoidant/Restrictive Food Intake Disorder Can Double Its Prevalence.

Objective: The DSM-5 criteria for avoidant/restrictive food intake disorder (ARFID) include ambiguities. Diagnostic criteria that allow for clinical judgment are essential for clinical practice. However, ambiguities can have major implications for treatment access and comparability and generalizability of research studies. The purpose of this study was to determine the degree to which distinct operationalizations of the diagnostic criteria for ARFID contribute to differences in the frequency of individuals who are eligible for the ARFID diagnosis.Methods: Because criteria B, C, and D are rule-outs, we focused on criterion A, identified 19 potential operational definitions, and determined the extent to which these different methods impacted the proportion of individuals who met criteria for ARFID in a sample of children, adolescents, and young adults (n = 80; September 2016-February 2020) enrolled in an avoidant/restrictive eating study.Results: Within each criterion, the proportion of individuals meeting diagnostic criteria differed significantly across the methodologies (all P values < .008). Using the strictest definition of each criterion, 50.0% (n = 40) of participants met criteria for ARFID. In contrast, under the most lenient definition of each criterion, the number nearly doubled, resulting in 97.5% (n = 78) meeting ARFID criteria.Conclusions: Comparison of diagnostic definitions for ARFID among children, adolescents, and young adults confirmed a broad range of statistically distinct proportions within a single sample. Our findings support the need for additional contextual support and consensus among disciplines on operationalization in both research and clinical settings.

Cognitive-behavioral therapy for adults with avoidant/restrictive food intake disorder.

There are currently no evidence-based treatments for adults with avoidant/restrictive food intake disorder (ARFID). The purpose of this study was to evaluate the acceptability, feasibility, and proof-of-concept of cognitive-behavioral therapy for ARFID (CBT-AR) for adults. Males and females (ages 18-55 years) were offered 20-30 outpatient sessions of CBT-AR delivered by one of five therapists. Of 18 eligible adults offered CBT-AR, 15 chose to participate and 14 completed treatment. All patients endorsed high ratings of treatment credibility and expected improvement after the first session, and 93% of completers provided high ratings of satisfaction at the conclusion of treatment. Therapists rated the majority (80%) of patients as "much improved" or "very much improved." Based on intent-to-treat analyses, ARFID severity on the Pica, ARFID, and Rumination Disorder Interview (PARDI) showed a large and significant decrease from pre- to post-treatment; and patients incorporated a mean of 18.0 novel foods. The underweight subgroup (n = 4) gained an average of 11.38 pounds, showing a large and significant increase in mean BMI from the underweight to the normal-weight range. At post-treatment, 47% of patients no longer met criteria for ARFID. To our knowledge, this is the first prospective treatment study of ARFID in adults. The findings of this study provide preliminary evidence of feasibility, acceptability, and proof-of-concept of CBT-AR for heterogeneous presentations of ARFID in adults. Randomized controlled trials are needed to confirm these findings. ClinicalTrials.gov Identifier: NCT02963220.

Cognitive-behavioral therapy for avoidant/restrictive food intake disorder: Feasibility, acceptability, and proof-of-concept for children and adolescents.

OBJECTIVE: Little is known about the optimal treatment of avoidant/restrictive food intake disorder (ARFID). The purpose of this study was to evaluate feasibility, acceptability, and proof-of-concept for cognitive-behavioral therapy for ARFID (CBT-AR) in children and adolescents. METHOD: Males and females (ages 10-17 years) were offered 20-30 sessions of CBT-AR delivered in a family-based or individual format. RESULTS: Of 25 eligible individuals, 20 initiated treatment, including 17 completers and 3 dropouts. Using intent-to-treat analyses, clinicians rated 17 patients (85%) as "much improved" or "very much improved." ARFID severity scores (on the Pica, ARFID, and Rumination Disorder Interview) significantly decreased per both patient and parent report. Patients incorporated a mean of 16.7 (SD = 12.1) new foods from pre- to post-treatment. The underweight subgroup showed a significant weight gain of 11.5 (SD = 6.0) pounds, moving from the 10th to the 20th percentile for body mass index. At post-treatment, 70% of patients no longer met criteria for ARFID. DISCUSSION: This is the first study of an outpatient manualized psychosocial treatment for ARFID in older adolescents. Findings provide evidence of feasibility, acceptability, and proof-of-concept for CBT-AR. Randomized controlled trials are needed.

Prevalence and correlates of psychiatric comorbidities in children and adolescents with full and subthreshold avoidant/restrictive food intake disorder.

OBJECTIVE: We aimed to characterize the current and lifetime prevalence of comorbid psychiatric diagnoses and suicidality in treatment- and nontreatment-seeking individuals with full and subthreshold avoidant/restrictive food intake disorder (ARFID). We also sought to examine unique associations between the three DSM-5 ARFID profiles (i.e., sensory sensitivity, fear of aversive consequences, and lack of interest in food or eating) and specific categories of psychiatric diagnoses and suicidality. METHOD: We conducted structured clinical interviews with 74 children and adolescents with full or sub threshold ARFID to assess the presence of comorbid psychiatric diagnoses, suicidality, and the severity of each of the three ARFID profiles. RESULTS: Nearly half of the sample (45%) met criteria for a current comorbid psychiatric diagnosis, and over half (53%) met criteria for a lifetime comorbid diagnosis. A total of 8% endorsed current suicidality and 14% endorsed lifetime suicidality. Severity in the sensory sensitivity profile was uniquely associated with greater odds of comorbid disorders in the neurodevelopmental, disruptive, and conduct disorders category; the anxiety, obsessive-compulsive, and trauma-related disorders category; and the depressive and bipolar-related disorders category. Severity in the fear of aversive consequences profile was associated with greater odds of disorders in the anxiety, obsessive-compulsive, and trauma-related disorders category. DISCUSSION: Our findings underscore the severity of psychopathology among individuals with ARFID and related presentations, and also highlight the potential that shared psychopathology between specific ARFID profiles and other psychiatric disorders represent transdiagnostic constructs (e.g., avoidant behavior) that may be relevant treatment targets.