Course of avoidant/restrictive food intake disorder: Emergence of overvaluation of shape/weight.

BACKGROUND: Avoidant/restrictive food intake disorder (ARFID) is a feeding/eating disorder characterized by avoidance/restriction of food intake by volume and/or variety. The emergence of shape/weight-related eating disorder symptoms in the longitudinal course of ARFID is an important clinical phenomenon that is neither robustly documented nor well understood. We aimed to characterize the emergence of eating disorder symptoms among adults with an initial diagnosis of ARFID who ultimately developed other eating disorders. METHOD: Thirty-five participants (94% female; Mage = 23.17 ± 5.84 years) with a history of ARFID and a later, separate eating disorder completed clinical interviews (i.e., Structured Clinical Interview for DSM-5 - Research Version and Longitudinal Interval Follow-Up Evaluation) assessing the period between ARFID and the later eating disorder. Participants used calendars to aid in recall of symptoms over time. Descriptive statistics characterized the presence, order of, and time to each symptom. Paired samples t-tests compared weeks to emergence between symptoms. RESULTS: Most participants (71%) developed restricting eating disorders; the remainder (29%) developed binge-spectrum eating disorders. Cognitive symptoms (e.g., shape/weight concerns) tended to onset initially and were followed by behavioral symptoms. Shape/weight-related food avoidance presented first, objective binge eating, fasting, and excessive exercise occurred next, followed by subjective binge eating and purging. CONCLUSIONS: Diagnostic crossover from ARFID to another (typically restricting) eating disorder following the development of shape/weight concerns may represent the natural progression of a singular clinical phenomenon. Findings identify potential pathways from ARFID to the development of another eating disorder, highlighting possible clinical targets for preventing this outcome.

Latent profile analysis reveals overlapping ARFID and shape/weight motivations for restriction in eating disorders.

BACKGROUND: DSM-5 differentiates avoidant/restrictive food intake disorder (ARFID) from other eating disorders (EDs) by a lack of overvaluation of body weight/shape driving restrictive eating. However, clinical observations and research demonstrate ARFID and shape/weight motivations sometimes co-occur. To inform classification, we: (1) derived profiles underlying restriction motivation and examined their validity and (2) described diagnostic characterizations of individuals in each profile to explore whether findings support current diagnostic schemes. We expected, consistent with DSM-5, that profiles would comprise individuals endorsing solely ARFID or restraint (i.e. trying to eat less to control shape/weight) motivations. METHODS: We applied latent profile analysis to 202 treatment-seeking individuals (ages 10-79 years [M = 26, s.d. = 14], 76% female) with ARFID or a non-ARFID ED, using the Nine-Item ARFID Screen (Picky, Appetite, and Fear subscales) and the Eating Disorder Examination-Questionnaire Restraint subscale as indicators. RESULTS: A 5-profile solution emerged: Restraint/ARFID-Mixed (n = 24; 8% [n = 2] with ARFID diagnosis); ARFID-2 (with Picky/Appetite; n = 56; 82% ARFID); ARFID-3 (with Picky/Appetite/Fear; n = 40; 68% ARFID); Restraint (n = 45; 11% ARFID); and Non-Endorsers (n = 37; 2% ARFID). Two profiles comprised individuals endorsing solely ARFID motivations (ARFID-2, ARFID-3) and one comprising solely restraint motivations (Restraint), consistent with DSM-5. However, Restraint/ARFID-Mixed (92% non-ARFID ED diagnoses, comprising 18% of those with non-ARFID ED diagnoses in the full sample) endorsed ARFID and restraint motivations. CONCLUSIONS: The heterogeneous profiles identified suggest ARFID and restraint motivations for dietary restriction may overlap somewhat and that individuals with non-ARFID EDs can also endorse high ARFID symptoms. Future research should clarify diagnostic boundaries between ARFID and non-ARFID EDs.

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).

Lower region-specific gray matter volume in females with atypical anorexia nervosa and anorexia nervosa.

OBJECTIVE: Few studies have focused on brain structure in atypical anorexia nervosa (atypical AN). This study investigates differences in gray matter volume (GMV) between females with anorexia nervosa (AN) and atypical AN, and healthy controls (HC). METHOD: Structural magnetic resonance imaging data were acquired for 37 AN, 23 atypical AN, and 41 HC female participants. Freesurfer was used to extract GMV, cortical thickness, and surface area for six brain lobes and associated cortical regions of interest (ROI). Primary analyses employed linear mixed-effects models to compare group differences in lobar GMV, followed by secondary analyses on ROIs within significant lobes. We also explored relationships between cortical gray matter and both body mass index (BMI) and symptom severity. RESULTS: Our primary analyses revealed significant lower GMV in frontal, temporal and parietal areas (FDR < .05) in AN and atypical AN when compared to HC. Lobar GMV comparisons were non-significant between atypical AN and AN. The parietal lobe exhibited the greatest proportion of affected cortical ROIs in both AN versus HC and atypical AN versus HC. BMI, but not symptom severity, was found to be associated with cortical GMV in the parietal, frontal, temporal, and cingulate lobes. No significant differences were observed in cortical thickness or surface area. DISCUSSION: We observed lower GMV in frontal, temporal, and parietal areas, when compared to HC, but no differences between AN and atypical AN. This indicates potentially overlapping structural phenotypes between these disorders and evidence of brain changes among those who are not below the clinical underweight threshold. PUBLIC SIGNIFICANCE: Despite individuals with atypical anorexia nervosa presenting above the clinical weight threshold, lower cortical gray matter volume was observed in partial, temporal, and frontal cortices, compared to healthy individuals. No significant differences were found in cortical gray matter volume between anorexia nervosa and atypical anorexia nervosa. This underscores the importance of continuing to assess and target weight gain in clinical care, even for those who are presenting above the low-weight clinical criteria.

Cognitive-behavioral therapy for avoidant/restrictive food intake disorder: A proof-of-concept for mechanisms of change and target engagement.

BACKGROUND: Cognitive-behavioral therapy for avoidant/restrictive food intake disorder (ARFID; CBT-AR) theoretically targets three prototypic motivations (sensory sensitivity, lack of interest/low appetite, fear of aversive consequences), aligned with three modularized interventions. As an exploratory investigation, we: (1) evaluated change in candidate mechanisms in relationship to change in ARFID severity, and (2) tested if assignment (vs. not) to a module resulted in larger improvements in the corresponding mechanism. METHOD: Males and females (N = 42; 10-55 years) participated in an open trial of CBT-AR. RESULTS: Decreases in scaled scores for each candidate mechanism had medium to large correlations with decreases in ARFID severity-sensory sensitivity: -0.7 decrease (r = .42, p = .01); lack of interest/low appetite: -0.3 decrease (r = .60, p < .0001); and fear of aversive consequences: -1.1 decrease (r = .33, p = .05). Linear mixed models revealed significant weekly improvements for each candidate mechanism across the full sample (ps < .0001). There were significant interactions for the sensory and fear of aversive consequences modules-for each, participants who received the corresponding module had significantly larger decreases in the candidate mechanism than those who did not receive the module. DISCUSSION: Sensory sensitivity and fear of aversive consequences improved more if the CBT-AR module was received, but lack of interest/low appetite may improve regardless of receipt of the corresponding module. Future research is needed to test target engagement in CBT-AR with adaptive treatment designs, and to identify valid and sensitive measures of candidate mechanisms. PUBLIC SIGNIFICANCE: The mechanisms through which components of CBT-AR work have yet to be elucidated. We conducted an exploratory investigation to test if assignment (vs. not) to a CBT-AR module resulted in larger improvements in the corresponding prototypic ARFID motivation that the module intended to target. Measures of the sensory sensitivity and the fear of aversive consequences motivations improved more in those who received the corresponding treatment module, whereas the lack of interest/low appetite measure improved regardless of if the corresponding module was received.

Avoidant/restrictive food intake disorder differs from anorexia nervosa in delay discounting.

BACKGROUND: Avoidant/restrictive food intake disorder (ARFID) and anorexia nervosa (AN) are the two primary restrictive eating disorders; however, they are driven by differing motives for inadequate dietary intake. Despite overlap in restrictive eating behaviors and subsequent malnutrition, it remains unknown if ARFID and AN also share commonalities in their cognitive profiles, with cognitive alterations being a key identifier of AN. Discounting the present value of future outcomes with increasing delay to their expected receipt represents a core cognitive process guiding human decision-making. A hallmark cognitive characteristic of individuals with AN (vs. healthy controls [HC]) is reduced discounting of future outcomes, resulting in reduced impulsivity and higher likelihood of favoring delayed gratification. Whether individuals with ARFID display a similar reduction in delay discounting as those with AN (vs. an opposing bias towards increased delay discounting or no bias) is important in informing transdiagnostic versus disorder-specific cognitive characteristics and optimizing future intervention strategies. METHOD: To address this research question, 104 participants (ARFID: n = 57, AN: n = 28, HC: n = 19) completed a computerized Delay Discounting Task. Groups were compared by their delay discounting parameter (ln)k. RESULTS: Individuals with ARFID displayed a larger delay discounting parameter than those with AN, indicating steeper delay discounting (M ± SD = -6.10 ± 2.00 vs. -7.26 ± 1.73, p = 0.026 [age-adjusted], Hedges' g = 0.59), with no difference from HC (p = 0.514, Hedges' g = -0.35). CONCLUSION: Our findings provide a first indication of distinct cognitive profiles among the two primary restrictive eating disorders. The present results, together with future research spanning additional cognitive domains and including larger and more diverse samples of individuals with ARFID (vs. AN), will contribute to identifying maintenance mechanisms that are unique to each disorder as well as contribute to the optimization and tailoring of treatment strategies across the spectrum of restrictive eating disorders.

Avoidant/restrictive food intake disorder (ARFID) and anorexia nervosa (AN) are both restrictive eating disorders. However, the reasons for restricting food intake differ between the two diagnoses. A key question in further understanding similarities and differences between ARFID and AN is to understand whether individuals with these disorders process information and make decisions in similar or distinct ways. When humans decide between two different outcomes (e.g., a smaller immediate or a larger delayed reward), outcomes decrease in their value the farther in the future we expect to receive them (delay discounting). Individuals with AN exhibit a reduced discounting of future outcomes, which makes them more likely to forego immediate gratification for later rewards. However, whether this holds true for individuals with ARFID too (or whether they show the opposite or no bias) is unknown. Our investigation is the first to compare delay discounting between individuals with ARFID, AN, and healthy controls (HC). Our results show that individuals with ARFID show more delay discounting than those with AN, with no difference from HC. Knowing how rewards are being chosen and decisions made (and knowing differences between diagnoses) will be helpful in further optimizing and tailoring treatments for restrictive eating disorders.

Anticipatory and consummatory pleasure in avoidant/restrictive food intake disorder.

BACKGROUND: Recent research suggests that individuals with eating disorders (EDs) report elevated anhedonia, or loss of pleasure. Although individuals with avoidant/restrictive food intake disorder (ARFID) often express that they do not look forward to eating, it is unclear whether they experience lower pleasure than those without EDs. Thus, identifying whether individuals with ARFID experience anhedonia may yield important insights that inform clinical conceptualization and treatment. METHODS: A sample of 71 participants ages 10-23 with full and subthreshold ARFID and 33 healthy controls (HCs) completed the Pica, ARFID, and Rumination Disorder Interview, a diagnostic interview to assess ARFID profile severity (lack of interest in food, sensory sensitivity, fear of aversive consequences) and the Temporal Experience of Pleasure Scale (TEPS), a self-report measure of consummatory and anticipatory pleasure. Statistical analyses were performed using the full TEPS and also the TEPS with food-related items removed. RESULTS: The ARFID group reported significantly lower anticipatory and consummatory pleasure compared to HCs, but these differences were no longer significant after controlling for depression, nor after removing food items from the TEPS. Within the ARFID sample, greater ARFID severity was associated with lower anticipatory pleasure across analyses, and greater endorsement of the lack of interest in food profile was related to lower anticipatory pleasure. ARFID severity was also associated with lower consummatory pleasure using the full TEPS, but this relationship was no longer significant with food items removed. CONCLUSIONS: These results provide initial evidence for lower pleasure before potentially pleasurable events in individuals with more severe ARFID, particularly those with the lack of interest phenotype. Our findings also suggest that depression is likely to contribute low pleasure in this population. Future research should seek to further characterize how dimensions of pleasure relate to the maintenance and treatment of ARFID symptoms.

Individuals with eating disorders often report elevated anhedonia, or an inability to experience pleasure. Past research on pleasure in eating disorders has focused primarily on individuals with anorexia nervosa and bulimia nervosa, and it is unclear whether people with other eating disorders also experience lower pleasure than healthy individuals. In the current study, we measured anticipatory pleasure (looking forward to something enjoyable) and consummatory pleasure (enjoying a pleasant stimulus) in a sample with avoidant/restrictive food intake disorder (ARFID) and healthy controls. We also repeated our analyses after removing food-related items from the scale assessing pleasure. The ARFID group scored lower on both dimensions of pleasure than controls, but this difference was primarily due to greater depression symptoms and the presence of food-related items in the pleasure questionnaire. Within the ARFID sample, individuals with more severe ARFID reported less anticipatory pleasure, even after removing questions about enjoyment of food. Lower anticipatory pleasure was especially characteristic of the lack of interest in eating phenotype of ARFID. These results suggest that ARFID severity, lack of interest in eating, and depression contribute to low pleasure in this population.

Oxytocin response to food intake in avoidant/restrictive food intake disorder.

OBJECTIVE: To investigate the response of anorexigenic oxytocin to food intake among adolescents and young adults with avoidant/restrictive food intake disorder (ARFID), a restrictive eating disorder characterized by lack of interest in food or eating, sensory sensitivity to food, and/or fear of aversive consequences of eating, compared with healthy controls (HC). DESIGN: Cross-sectional. METHODS: A total of 109 participants (54 with ARFID spectrum and 55 HC) were instructed to eat a ∼400-kcal standardized mixed meal. We sampled serum oxytocin at fasting and at 30-, 60-, and 120-min postmeal. We tested the hypothesis that ARFID would show higher mean oxytocin levels across time points compared with HC using a mixed model ANOVA. We then used multivariate regression analysis to identify the impact of clinical characteristics (sex, age, and body mass index [BMI] percentile) on oxytocin levels in individuals with ARFID. RESULTS: Participants with ARFID exhibited greater mean oxytocin levels at all time points compared with HC, and these differences remained significant even after controlling for sex and BMI percentile (P = .004). Clinical variables (sex, age, and BMI percentile) did not show any impact on fasting and postprandial oxytocin levels among individuals with ARFID. CONCLUSIONS: Consistently high oxytocin levels might be involved in low appetite and sensory aversions to food, contributing to food avoidance in individuals with ARFID.

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.

Neural activation of regions involved in food reward and cognitive control in young females with anorexia nervosa and atypical anorexia nervosa versus healthy controls.

Anorexia nervosa (AN) and atypical AN (AtypAN) are complex neurobiological illnesses that typically onset in adolescence with an often treatment-refractory and chronic illness trajectory. Aberrant eating behaviors in this population have been linked to abnormalities in food reward and cognitive control, but prior studies have not examined respective contributions of clinical characteristics and metabolic state. Research is needed to identify specific disruptions and inform novel intervention targets to improve outcomes. Fifty-nine females with AN (n = 34) or AtypAN (n = 25), ages 10-22 years, all ≤90% expected body weight, and 34 age-matched healthy controls (HC) completed a well-established neuroimaging food cue paradigm fasting and after a standardized meal, and we used ANCOVA models to investigate main and interaction effects of Group and Appetitive State on blood oxygenation level-dependent (BOLD) activation for the contrast of exposure to high-calorie food images minus objects. We found main effects of Group with greater BOLD activation in the dorsal anterior cingulate cortex (dACC), dorsolateral prefrontal cortex (DLPFC), hippocampus, caudate, and putamen for AN/AtypAN versus HC groups, and in the three-group model including AN, AtypAN, and HC (sub-)groups, where differences were primarily driven by greater activation in the AtypAN subgroup versus HC group. We found a main effect of Appetitive State with increased premeal BOLD activation in the hypothalamus, amygdala, nucleus accumbens, and caudate for models that included AN/AtypAN and HC groups, and in BOLD activation in the nucleus accumbens for the model that included AN, AtypAN, and HC (sub-)groups. There were no interaction effects of Group with Appetitive State for any of the models. Our findings demonstrate robust feeding-state independent group effects reflecting greater neural activation of specific regions typically associated with reward and cognitive control processing across AN and AtypAN relative to healthy individuals in this food cue paradigm. Differential activation of specific brain regions in response to the passive viewing of high-calorie food images may underlie restrictive eating behavior in this clinical population.

Lower Ghrelin Levels Are Associated With Higher Anxiety Symptoms in Adolescents and Young Adults With Avoidant/Restrictive Food Intake Disorder.

Objective: Avoidant/restrictive food intake disorder (ARFID) is associated with increased risk for anxiety, which may adversely affect prognosis. The appetite-stimulating hormone, ghrelin, increases in response to stress, and exogenous ghrelin decreases anxiety-like behaviors in animal models. The aim of this study was to evaluate the relationship between ghrelin levels and measures of anxiety in youth with ARFID. We hypothesized that lower ghrelin levels would be associated with increased anxiety symptoms.Methods: We studied a cross-sectional sample of 80 subjects with full and subthreshold ARFID diagnosed by DSM-5 criteria, aged 10-23 years (female, n = 39; male, n = 41). Subjects were enrolled in a study of the neurobiology of avoidant/restrictive eating conducted from August 2016 to January 2021. We assessed fasting ghrelin levels and anxiety symptoms (State-Trait Anxiety Inventory [STAI] and STAI for Children [STAI-C] measuring general trait anxiety; Beck Anxiety Inventory [BAI] and BAI for youth [BAI-Y] assessing cognitive, emotional, and somatic symptoms of anxiety; and Liebowitz Social Anxiety Scale [LSAS] assessing symptoms of social anxiety).Results: Consistent with our hypothesis, ghrelin levels were inversely associated with anxiety symptoms as assessed by STAI/STAI-C T scores (r = -0.28, P = .012), BAI/BAI-Y T scores (r = -0.28, P = .010), and LSAS scores (r = -0.3, P = .027), all with medium effect sizes. Findings held in the full threshold ARFID group when adjusting for body mass index z scores (STAI/STAI-C T scores, ß = -0.27, P = .024; BAI/BAI-Y T scores, ß = -0.26, P = .034; LSAS, ß = -0.34, P = .024).Conclusions: These findings demonstrate that lower levels of ghrelin are associated with more severe anxiety symptoms in youth with ARFID and raise the question of whether ghrelin pathways could be targeted in the treatment of ARFID.

Development of a brief cognitive-behavioral treatment for avoidant/restrictive food intake disorder in the context of disorders of gut-brain interaction: Initial feasibility, acceptability, and clinical outcomes.

BACKGROUND: Avoidant/restrictive food intake disorder (ARFID) symptoms are common (up to 40%) among adults with disorders of gut-brain interaction (DGBI), but treatments for this population (DGBI + ARFID) have yet to be evaluated. We aimed to identify initial feasibility, acceptability, and clinical effects of an exposure-based cognitive-behavioral treatment (CBT) for adults with DGBI + ARFID. METHODS: Patients (N = 14) received CBT as part of routine care in an outpatient gastroenterology clinic. A two-part investigation of the CBT included a retrospective evaluation of patients who were offered a flexible (8-10) session length and an observational prospective study of patients who were offered eight sessions. Feasibility benchmarks were ≥75% completion of sessions, quantitative measures (for treatment completers), and qualitative interviews. Acceptability was assessed with a benchmark of ≥70% patients reporting a posttreatment satisfaction scores ≥3 on 1-4 scale and with posttreatment qualitative interviews. Mixed model analysis explored signals of improvement in clinical outcomes. RESULTS: All feasibility and acceptability benchmarks were achieved (and qualitative feedback revealed high satisfaction with the treatment and outcomes). There were improvements in clinical outcomes across treatment (all p's < .0001) with large effects for ARFID fear (-52%; Hedge's g = 1.5; 95% CI = 0.6, 2.5) and gastrointestinal-specific anxiety (-42%; Hedge's g = 1.0; 95% CI = 0.5, 16). Among those who needed to gain weight (n = 10), 94%-103% of expected weight gain goals were achieved. DISCUSSION: Initial development and testing of a brief 8-session CBT protocol for DGBI + ARFID showed high feasibility, acceptability, and promising clinical improvements. Findings will inform an NIH Stage 1B randomized control trial. PUBLIC SIGNIFICANCE: While cognitive-behavioral treatments (CBTs) for ARFID have been created in outpatient feeding and eating disorder clinics, they have yet to be developed and refined for other clinic settings or populations. In line with the recommendations for behavioral treatment development, we conducted a two-part investigation of an exposure-based CBT for a patient population with high rates of ARFID-adults with disorders of gut-brain interaction (also known as functional gastrointestinal disorders). We found patients had high satisfaction with treatment and there were promising improvements for both gastrointestinal and ARFID outcomes. The refined treatment includes eight sessions delivered by a behavioral health care provider and the findings reported in this article will be studied next in an NIH Stage 1B randomized controlled trial.

The factor structure and validity of a diagnostic interview for avoidant/restrictive food intake disorder in a sample of children, adolescents, and young adults.

OBJECTIVE: There is a paucity of validated diagnostic interviews for avoidant/restrictive food intake disorder (ARFID) to aid identification and classification of cases for both clinical and research purposes. To evaluate the factor structure, construct validity, and criterion validity of the Pica ARFID and Rumination Disorder Interview (PARDI; ARFID module), we administered the PARDI to 129 children and adolescents ages 9-23 years (M = 16.1) with ARFID (n = 84), subclinical ARFID (n = 11), and healthy controls (n = 34). METHOD: We used exploratory factor analysis to examine the factor structure of the PARDI in children, adolescents, and young adults with an ARFID diagnosis, the Kruskal-Wallis analysis of variance and Spearman correlations to test the construct validity of the measure, and non-parametric receiver operating characteristic curves to evaluate the criterion validity of the PARDI. RESULTS: Exploratory factor analysis yielded a 3-factor structure: (1) concern about aversive consequences of eating, (2) low appetite/low interest in food, and (3) sensory sensitivity. Participants with ARFID demonstrated significantly higher levels of sensory sensitivity, low appetite/low-food interest, and concern about aversive consequences of eating symptoms relative to control participants. The construct validity for each PARDI subscale was supported and clinical cutoffs for the low appetite/low interest in food (1.1) and sensory sensitivity subscales (0.6) were established. DISCUSSION: These data present evidence for the factor structure and validity of the PARDI diagnostic interview for diagnosing ARFID in children, adolescents, and young adults, supporting the use of this tool to facilitate ARFID clinical assessment and research. PUBLIC SIGNIFICANCE: Due to the paucity of validated diagnostic interviews for avoidant/restrictive food intake disorder (ARFID), we evaluated the factor structure and validity of the Pica ARFID and Rumination Disorder Interview (ARFID module). Findings suggest that the interview assesses 3 components of ARFID: concern about aversive consequences of eating, low-appetite, and sensory sensitivity, and that clinical threshold scores on the latter two subscales can be used to advance ARFID assessment.

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.

Food neophobia as a mechanism of change in video-delivered cognitive-behavioral therapy for avoidant/restrictive food intake disorder: A case study.

OBJECTIVE: The mechanisms through which cognitive-behavioral therapies (CBTs) for avoidant/restrictive food intake disorder (ARFID) may work have yet to be elucidated. To inform future treatment revisions to increase parsimony and potency of CBT for ARFID (CBT-AR), we evaluated change in food neophobia during CBT-AR treatment of a sensory sensitivity ARFID presentation via a single case study. METHOD: An adolescent male completed 21, twice-weekly sessions of CBT-AR via live video delivery. From pre- to mid- to post-treatment and at 2-month follow-up, we calculated percent change in food neophobia and ARFID symptom severity measures. Via visual inspection, we explored trajectories of week-by-week food neophobia in relation to clinical improvements (e.g., when the patient incorporated foods into daily life). RESULTS: By post-treatment, the patient achieved reductions across food neophobia (45%), and ARFID severity (53-57%) measures and no longer met criteria for ARFID, with sustained improvement at 2-month follow-up. Via visual inspection of week-by-week food neophobia trajectories, we identified that decreases occurred after mid-treatment and were associated with incorporation of a food directly tied to the patient's main treatment motivation. DISCUSSION: This study provides hypothesis-generating findings on candidate CBT-AR mechanisms, showing that changes in food neophobia were related to food exposures most connected to the patient's treatment motivations. PUBLIC SIGNIFICANCE: Cognitive-behavioral therapies (CBTs) can be effective for treating avoidant/restrictive food intake disorder (ARFID). However, we do not yet have evidence to show how they work. This report of a single patient shows that willingness to try new foods (i.e., food neophobia), changed the most when the patient experienced a clinical improvement most relevant to his motivation for seeking treatment.

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.

Meta-analysis of structural MRI studies in anorexia nervosa and the role of recovery: a systematic review protocol.

BACKGROUND: Anorexia nervosa (AN) is associated with structural brain abnormalities. Studies have reported less cerebral tissue and more cerebrospinal fluid (CSF) in individuals with AN relative to healthy controls, although findings are variable and inconsistent due to variations in sample size, age, and disease state (e.g., active AN, weight-recovered AN). Further, it remains unclear if structural brain abnormalities observed in AN are a consequence of specific brain pathologies or malnutrition, as very few longitudinal neuroimaging studies in AN have been completed. METHODS: To overcome this issue, this comprehensive meta-analysis will combine region-of-interest (ROI) and voxel-based morphometry (VBM) approaches to understand how regional and global structural brain abnormalities differ among individuals with AN and healthy controls (HCs). Additionally, we aim to understand how clinical characteristics and physiological changes during the course of illness, including acute illness vs. weight recovery, may moderate these structural abnormalities. We will create an online database of studies that have investigated structural brain abnormalities in AN. Data will be reviewed independently by two members of our team using MEDLINE databases, Web of Science, PsycINFO, EMBASE, and CINAHL. We will conduct ROI and VBM meta-analysis using seed-based d mapping in AN and HCs. We will include all studies that include structural neuroimaging of individuals with AN (both acute and weight-recovered) and HCs between January 1997 and 2020. DISCUSSION: This systematic review will assess the effects of AN compared to HC on brain structure. Futhermore, it will explore the role of acute AN and weight-recovered AN on brain structure. Findings will help researchers and clinicians to better understand the course of illness in AN and the nature of recovery, in terms of weight, malnutrition, and the state of the brain. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020180921.