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Objective: Despite substantial research indicating difficulties with emotion regulation across eating disorder presentations, emotion regulation has yet to be studied in adults with avoidant/restrictive food intake disorder (ARFID). We hypothesized that (1) those with ARFID would report greater overall emotion regulation difficulties than nonclinical participants, and (2) those with ARFID would not differ from those with other eating disorders on the level of emotion regulation difficulty., Methods: One hundred and thirty-seven adults (age 18-30) from an outpatient clinic with ARFID (n = 27), with other primarily restrictive eating disorders (e.g., anorexia nervosa; n = 34), and with binge/purge eating disorders (e.g., bulimia nervosa; n = 51), as well as nonclinical participants (n = 25) recruited via Amazon Mechanical Turk (MTurk) completed the Difficulties in Emotion Regulation Scale (DERS). We compared DERS scores across groups., Results: In line with expectations, patients with ARFID scored significantly higher than nonclinical participants on the DERS Total (p = 0.01) with a large effect size (d = 0.87). Also as hypothesized, those with ARFID did not differ from those with other primarily restrictive (p = 0.99) or binge/purge disorders (p = 0.29) on DERS Total., Discussion: Adults with ARFID appear to exhibit emotion regulation difficulties which are greater than nonclinical participants, and commensurate with other eating disorders. These findings highlight the possibility of emotion regulation difficulties as a maintenance mechanism for ARFID., (© 2024 Wiley Periodicals LLC.)

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., Competing Interests: Declaration of Competing Interest Drs. Thomas and Eddy receive royalties from Cambridge University Press for the sale of their book, Cognitive- Behavioral Therapy for Avoidant/Restrictive Food Intake Disorder: Children, Adolescents, and Adults. Drs. Thomas, Eddy and Becker receive royalties from Cambridge University Press for the sale of their book The Picky Eater’s Recovery Book: Overcoming Avoidant/Restrictive Food Intake Disorder. Drs. Lawson and Misra receive royalties from UpToDate. Dr. Lawson was on the scientific advisory board and has/had a financial interest in OXT Therapeutics, a company that developed oxytocin-based therapeutics for metabolic disease; and receives research funding from Tonix Pharmaceuticals. Dr. Misra reports receiving personal fees from AbbVie, Ipsen, and Sanofi. Dr. Breithaupt reports receiving personal fees from Otsuka Pharmaceutical. Drs. Burton Murray and Thomas receive royalties from Oxford University Press for her forthcoming book on rumination syndrome. No other authors declare competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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., (© 2024 Wiley Periodicals LLC.)

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.

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 years 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 the ARFID profiles (ie, sensory sensitivity, fear of aversive consequences, lack of interest)., (Copyright © 2024. Published by Elsevier Inc.)

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; M age = 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., (© 2024. The Author(s).)

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., (© 2024 Wiley Periodicals LLC.)

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., (© 2024 Wiley Periodicals LLC.)

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., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

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., (© 2023. The Author(s).)

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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 (β = -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., (© 2023. The Author(s).)

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., (© 2023. The Author(s).)

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, β = -0.27, P  = .024; BAI/BAI-Y T scores, β = -0.26, P  = .034; LSAS, β = -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., (© Copyright 2023 Physicians Postgraduate Press, Inc.)

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., (© 2022 Wiley Periodicals LLC.)

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., (© 2022. The Author(s).)

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., (© 2022 The Authors. International Journal of Eating Disorders published by Wiley Periodicals LLC.)

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., (© 2022 Wiley Periodicals LLC.)

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.

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., (© 2022 Wiley Periodicals LLC.)

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 ( F 1  = 25.0, P  < .001, η p 2  = 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., (© Copyright 2022 Physicians Postgraduate Press, Inc.)

Objective: The Nine Item Avoidant/Restrictive Food Intake Disorder (ARFID) Screen (NIAS) has three subscales aligned with ARFID presentations but clinically validated cutoff scores have not been identified. We aimed to examine NIAS subscale (picky eating, appetite, fear) validity to: (1) capture clinically-diagnosed ARFID presentations; (2) differentiate ARFID from other eating disorders (other-ED); and (3) capture ARFID symptoms among individuals with ARFID, individuals with other-ED, and nonclinical participants., Method: Participants included outpatients (ages 10-76 years; 75% female) diagnosed with ARFID (n = 49) or other-ED (n = 77), and nonclinical participants (ages 22-68 years; 38% female, n = 40). We evaluated criterion-related concurrent validity by conducting receiver operating curve (ROC) analyses to identify potential subscale cutoffs and by testing if cutoffs could capture ARFID with and without use of the Eating Disorder Examination-Questionnaire (EDE-Q)., Results: Each NIAS subscale had high AUC for capturing those who fit versus do not fit each ARFID presentation, resulting in proposed cutoffs of ≥10 (sensitivity = .97, specificity = .63), ≥9 (sensitivity = .86, specificity = .70), and ≥ 10 (sensitivity = .68, specificity = .89) on the NIAS-picky eating, NIAS-appetite, and NIAS-fear subscales, respectively. ARFID versus other-ED had high AUC on the NIAS-picky eating (≥10 proposed cutoff), but not NIAS-appetite or NIAS-fear subscales. NIAS subscale cutoffs had a high association with ARFID diagnosis, but only correctly classified other-ED in combination with EDE-Q Global <2.3., Discussion: To screen for ARFID, we recommend using a screening tool for other-ED (e.g., EDE-Q) in combination with a positive score on any NIAS subscale (i.e., ≥10, ≥9, and/or ≥10 on the NIAS-picky eating, NIAS-appetite, and NIAS-fear subscales, respectively)., (© 2021 Wiley Periodicals LLC.)

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., (© 2021. The Author(s).)

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., (© Copyright 2021 Physicians Postgraduate Press, Inc.)

Background: Avoidant/restrictive food intake disorder (ARFID) is characterized by restrictive eating and failure to meet nutritional needs but is distinct from anorexia nervosa (AN) because restriction is not motivated by weight/shape concerns. We examined levels of orexigenic ghrelin and anorexigenic peptide YY (PYY) in young females with ARFID, AN and healthy controls (HC)., Methods: 94 females (22 low-weight ARFID, 40 typical/atypical AN, and 32 HC ages 10-22 years) underwent fasting blood draws for total ghrelin and total PYY. A subset also provided blood 30, 60 and 120 min after a standardized meal., Results: Females with ARFID ate less than those with AN or HC (ps<0.012); were younger (14.4 ± 3.2 years) than those with AN (18.9 ± 3.1 years) and HC (17.4 ± 3.1 years) (ps<0.003) and at a lower Tanner stage (3.1 ± 1.5) than AN (4.5 ± 1.1;) and HC (4.4 ± 1.1; ps<0.005), but did not differ in BMI percentiles or BMI Z-scores from AN (ps>0.44). Fasting and postprandial ghrelin were lower in ARFID versus AN (ps≤.015), but not HC (ps≥0.62). Fasting and postprandial PYY did not differ between ARFID versus AN or HC (ps≥0.13); ARFID did not demonstrate the sustained high PYY levels post-meal observed in those with AN and HC. Secondary analyses controlling age or Tanner stage and calories consumed showed similar results. Exploratory analyses suggest that the timing of the PYY peak in ARFID is earlier than HC, showing a peak PYY level 30 min post-meal (p = .037)., Conclusions: ARFID and AN appear to have distinct patterns of secretion of gut-derived appetite-regulating hormones that may aid in differential diagnosis and provide new treatment targets., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Cognitive inflexibility and attention to detail bias represent a promising target in eating disorder (ED) treatment. While prior research has found that adults with eating disorders exhibit significant cognitive inflexibility and heightened attention to detail, less is known about these cognitive impairments among adolescents, and across EDs transdiagnostically. To address this gap, adolescent females ( N = 143) from a residential ED program with anorexia nervosa, bulimia nervosa, or other specified feeding or eating disorder completed the Detail and Flexibility Questionnaire (DFlex) and measures of ED and general psychopathology. Transdiagnostically, adolescents with EDs scored higher than an archival sample of healthy control adolescents on both cognitive rigidity ( p < .001; Cohen's d = 1.92) and attention to detail ( p < .001; Cohen's d = 1.16). These cognitive impairments were significantly associated with severity of eating pathology, and these relationships existed independent of age, duration of illness, or body mass index (BMI). Our findings suggest cognitive inflexibility and heightened attention to detail occur transdiagnostically in adolescents with eating disorders and are unlikely to be a scar of the disorder. Future prospective research is needed to determine whether these cognitive styles represent an endophenotype of eating disorders.

Posttraumatic stress disorder (PTSD) and eating disorders (EDs) are individually debilitating and highly comorbid conditions. Childhood abuse is a prominent risk factor for PTSD and ED symptoms both individually and as a comorbid syndrome (PTSD-ED). There may be a functional association between comorbid PTSD-ED symptoms whereby disordered eating behaviors are used to avoid trauma-related thoughts and feelings. The current study used a network analytic approach to examine key associations between PTSD and ED symptom subscales (i.e., PCL-5 and EPSI, respectively) in a community sample of 120 adults who endorsed at least one experience of childhood abuse (i.e., physical, sexual, or emotional abuse; witnessing domestic violence). Participants completed an anonymous online survey using Amazon's Mechanical Turk Prime. We used three network analysis indices (i.e., strength centrality, key players, and bridge symptoms) to identify symptoms that may maintain the comorbid PTSD-ED network. The results indicated that reexperiencing symptoms had the highest strength centrality in the PTSD-ED network and bridged the PTSD and ED clusters. For ED, cognitive restraint was a bridge to all PTSD symptoms. Hyperarousal, negative alterations in cognitions and mood (NACM), and purging were key players, indicating they are integral to the network structure. If replicated in prospective studies, these results may indicate that reexperiencing and cognitive restraint are core drivers of PTSD-ED comorbidity, whereas hyperarousal, NACM, and purging may be downstream consequences maintaining the comorbid condition. Concurrent treatments that address PTSD and ED symptoms simultaneously may result in the best outcomes., (© 2020 International Society for Traumatic Stress Studies.)

Objective: Little research exists on Rome IV disorders of gut-brain interaction (DGBI; formerly called functional gastrointestinal disorders) in outpatients with eating disorders (EDs). These data are particularly lacking for avoidant/restrictive food intake disorder (ARFID), which shares core features with DGBI. We aimed to identify the frequency and nature of DGBI symptoms among outpatients with EDs., Method: Consecutively referred pediatric and adult patients diagnosed with an ED (n = 168, 71% female, ages 8-76 years) in our tertiary care ED program between March 2017 and July 2019 completed a modified Rome IV Questionnaire for DGBI and psychopathology measure battery., Results: The majority (n = 122, 72%) of participants reported at least one bothersome gastrointestinal symptom. Sixty-six (39%) met criteria for a DBGI, most frequently functional dyspepsia-post-prandial distress syndrome subtype (31%). DGBI were surprisingly less frequent among patients with ARFID (30%) versus EDs that are associated with shape or weight concerns (45%; X 2 [1] = 3.61, p = .058, Cramer's V = .147). Among those with ARFID, DGBI presence was associated with the fear of aversive consequences prototype and multiple comorbid prototype presence., Discussion: We demonstrated notable overlap between DGBI and EDs, particularly post-prandial distress symptoms. Further research is needed to examine if gastrointestinal symptoms predict or are a result of greater ED pathology, including ARFID prototypes., (© 2020 Wiley Periodicals LLC.)

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., Competing Interests: Disclosure of interest JJT, KTE, and KRB receive royalties from Cambridge University Press for the sale of their books on ARFID. All other authors declare that they have no competing interest.

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., (© 2020 Wiley Periodicals LLC.)

Introduction: Disruptions in homeostatic and hedonic food motivation are proposed to underlie anorexia nervosa (AN) and atypical AN, restrictive eating disorders which commonly onset in puberty. Ghrelin, a neuroprotective hormone that drives hedonic eating is increased in AN and is expressed in the hippocampus. White matter (WM) undergoes significant change during puberty in regions involved in food motivation, particularly WM tracts connected with the hippocampus. The association between ghrelin and WM region of interest (ROI) with hippocampal connections in restrictive eating disorders, particularly in adolescence during key neurodevelopmental growth, is unknown., Methods: We evaluated fasting plasma ghrelin and WM microstructure (measured by free-water corrected fractional anisotropy (FA-t)) in WM ROIs with hippocampal connections - the fornix and the hippocampal portion of the cingulum - in 56 adolescent females (age range: 11.9 - 22.1 y; mean: 19.0 y) with low-weight eating disorders including AN and atypical AN (N = 36) and healthy controls (N = 20)., Results: FA-t in the fornix or hippocampal portion of the fornix did not differ between groups. Ghrelin was higher in AN/atypical AN vs. HC and was positively correlated with puberty stage in the AN/atypical AN group, but not the HC group. The correlation between ghrelin and FA-t in the fornix was significantly different in females with AN/atypical AN compared to controls. In AN/atypical AN, pubertal stage moderated the relation between fasting plasma ghrelin and FA-t in the fornix: higher fasting ghrelin was associated with lower FA-t in the fornix in late-post-puberty, but was not associated with FA-t in the early to mid stages of puberty., Conclusions: In post-pubertal females with low-weight AN/atypical AN, higher levels of ghrelin are associated with lower FA-t in the fornix. This relationship is not evident in the early to mid stages of puberty in AN/atypical AN or in HC, and may reflect a lack of possible neuroprotective effects of ghrelin in late-post puberty only. Understanding the effects of ghrelin on WM microstructure longitudinally and following recovery from AN/Atypical AN and how this differs across pubertal stages will be an important next step. These findings could ultimately inform treatment staging and aid in diagnosis and detection of AN/atypical AN., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Females with anorexia nervosa (AN) have higher ghrelin and peptide YY (PYY) and lower brain-derived neurotropic factor (BDNF) levels than controls, and differ in their perception of hunger cues. Studies have not examined appetite-regulating hormones in the context of homeostatic and hedonic appetite in AN., Objective: To examine whether alterations in appetite-regulating hormones following a standardized meal are associated with homeostatic and hedonic appetite in young females with AN vs. controls., Methods: 68 females (36 AN, 32 controls) 10-22 years old were enrolled. Ghrelin, PYY and BDNF levels were assessed before, and 30, 60 and 120 min following a 400-kilocalorie standardized breakfast. Visual Analog Scales (VAS) assessing prospective food consumption, hunger, satiety, and hedonic appetite were administered before and 20 min after breakfast. A Cookie Taste Test (CTT) was conducted after a snack as a measure of hedonic eating behavior ∼3 h after breakfast., Results: AN had higher fasting ghrelin and PYY, and lower fasting BDNF (p = 0.001, 0.002 and 0.044 respectively) than controls. Following breakfast (over 120 min), ghrelin and PYY area under the curve (AUC) were higher, while BDNF AUC was lower in AN vs. controls (p = 0.007, 0.017 and 0.020 respectively). Among AN (but not controls), reductions in ghrelin and increases in PYY in the first 30-minutes following breakfast were associated with reductions in VAS scores for prospective food consumption. AN consumed fewer calories during the CTT vs. controls (p < 0.0001). In AN (particularly AN-restrictive subtype), BDNF AUC was positively associated with kilocalories consumed during the CTT CONCLUSIONS: In young females with AN, changes in ghrelin and PYY following food intake are associated with reductions in a prospective measure of food consumption, while reductions in BDNF are associated with reduced hedonic food intake. Further studies are necessary to better understand the complex interplay between appetite signals and eating behaviors in AN., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: This study examined the relationship between eating-disorder behaviors-including restrictive eating, binge eating, and purging-and suicidal ideation. We hypothesized that restrictive eating would significantly predict suicidal ideation, beyond the effects of binge eating/purging., Methods: Participants were 82 adolescents and young adults with low-weight eating disorders. We conducted a hierarchical logistic regression, with binge eating and purging in Step 1 and restrictive eating in Step 2, to predict suicidal ideation., Results: Step 1 was significant (p = .01) and explained 20% variance in suicidal ideation; neither binge eating nor purging significantly predicted suicidal ideation. Adding restrictive eating in Step 2 significantly improved the model (ΔR 2 = .07, p = .009). This final model explained 27% of the variance, and restrictive eating (but not binge eating/purging) significantly predicted suicidal ideation (p = .02)., Discussion: Restrictive eating is associated with suicidal ideation in youth with low-weight eating disorders, beyond the effects of other eating-disorder behaviors. Although healthcare providers may be more likely to screen for suicidality in patients with binge eating and purging, our findings indicate clinicians should regularly assess suicide and self-injury in patients with restrictive eating. Future research examining how individuals progress from suicidal ideation to suicidal attempts can further enhance our understanding of suicide in eating disorders., (© 2019 Wiley Periodicals, Inc.)

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., (© 2019 Wiley Periodicals, Inc.)

Objective: The cognitive-behavioral therapy (CBT) model of eating disorders suggests that compensatory purging behaviors (e.g., self-induced vomiting, inappropriate laxative use) are primarily driven by binge eating. However, many individuals endorse purging in the absence of binge eating (i.e., noncompensatory purging [NCP]). Research is needed to understand why some individuals purge in the absence of objective or subjective binge-eating episodes., Method: Given the importance of overvaluation of shape/weight in the CBT model, and the existing evidence linking temperamental characteristics like behavioral inhibition (i.e., the tendency to withdraw in response to threat cues) with purging in general, we tested whether behavioral inhibition moderated the relationship between overvaluation of shape/weight and NCP in a sample of individuals in a residential eating disorder treatment center (N = 143)., Results: Overvaluation was more strongly related to NCP in individuals with high (relative to low) levels of behavioral inhibition. Among individuals low in behavioral inhibition, overvaluation predicted engagement in NCP to a much weaker extent., Discussion: For those high (relative to low) in behavioral inhibition, both emotional avoidance and overvaluation may be important targets in the treatment of NCP, particularly in the absence of binge eating., (© 2019 Wiley Periodicals, Inc.)

Background: Psychiatric comorbidity is common in eating disorders (EDs) and associated with poor outcomes, including increased risk for relapse and premature death. Yet little is known about comorbidity following ED recovery., Methods: We examined two common comorbidities, major depressive disorder (MDD) and substance use disorder (SUD), in adult women with intake diagnoses of anorexia nervosa and bulimia nervosa who participated in a 22-year longitudinal study. One hundred and seventy-six of 228 surviving participants (77.2%) were interviewed 22 years after study entry using the Eating Disorders Longitudinal Interval Follow-up Evaluation to assess ED recovery status. Sixty-four percent (n = 113) were recovered from their ED. The Structured Clinical Interview for DSM-IV was used to assess MDD and SUD at 22 years., Results: At 22-year follow-up, 28% (n = 49) met criteria for MDD, and 6% (n = 11) met criteria for SUD. Those who recovered from their ED were 2.17 times more likely not to have MDD at 22-year follow-up (95% CI [1.10, 4.26], p = .023) and 5.33 times more likely not to have a SUD at 22-year follow-up than those who had not recovered from their ED (95% CI [1.36, 20.90], p = .008)., Conclusion: Compared to those who had not fully recovered from their ED, those who had recovered were twice as likely not to be diagnosed with MDD in the past year and five times as likely not to be diagnosed with SUDs in the past year. These findings provide evidence that long-term recovery from EDs is associated with recovery from or absence of these common major comorbidities. Because comorbidity in EDs can predict poor outcomes, including greater risk for relapse and premature death, our findings of reduced risk for psychiatric comorbidity following recovery at long-term follow-up is cause for optimism., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The majority of individuals with anorexia nervosa (AN) have a fat-phobic (FP-AN) presentation in which they explicitly endorse fear of weight gain, but a minority present as non-fat-phobic (NFP-AN). Diagnostic criteria for avoidant/restrictive food intake disorder (ARFID) specifically exclude fear of weight gain. Differential diagnosis between NFP-AN and ARFID can be challenging and explicit endorsements do not necessarily match internal beliefs., Method: Ninety-four adolescent females (39 FP-AN, 13 NFP-AN, 10 low-weight ARFID, 32 healthy controls [HC]) completed implicit association tests (IATs) categorizing statements as pro-dieting or non-dieting and true or false (questionnaire-based IAT), and images of female models as underweight or normal-weight and words as positive or negative (picture-based IAT). We used the Eating Disorder Examination to categorize FP- versus NFP-AN presentations., Results: Individuals with FP-AN and NFP-AN demonstrated a stronger association between pro-dieting and true statements, whereas those with ARFID and HCs demonstrated a stronger association between pro-dieting and false statements. Furthermore, while all groups demonstrated a negative implicit association with underweight models, HC participants had a significantly stronger negative association than individuals with FP-AN and NFP-AN., Discussion: Individuals with NFP-AN exhibited a mixed pattern in which some of their implicit associations were consistent with their explicit endorsements, whereas others were not, possibly reflecting a minimizing response style on explicit measures. In contrast, individuals with ARFID demonstrated implicit associations consistent with explicit endorsements. Replication studies are needed to confirm whether the questionnaire-based IAT is a promising method of differentiating between restrictive eating disorders that share similar clinical characteristics., (© 2018 Wiley Periodicals, Inc.)

Objective: Since its introduction to the psychiatric nomenclature in 2013, research on avoidant/restrictive food intake disorder (ARFID) has proliferated highlighting lack of clarity in how ARFID is defined., Method: In September 2018, a small multi-disciplinary pool of international experts in feeding disorder and eating disorder clinical practice and research convened as the Radcliffe ARFID workgroup to consider operationalization of DSM-5 ARFID diagnostic criteria to guide research in this disorder., Results: By consensus of the Radcliffe ARFID workgroup, ARFID eating is characterized by food avoidance and/or restriction, involving limited volume and/or variety associated with one or more of the following: weight loss or faltering growth (e.g., defined as in anorexia nervosa, or by crossing weight/growth percentiles); nutritional deficiencies (defined by laboratory assay or dietary recall); dependence on tube feeding or nutritional supplements (≥50% of daily caloric intake or any tube feeding not required by a concurrent medical condition); and/or psychosocial impairment., Conclusions: This article offers definitions on how best to operationalize ARFID criteria and assessment thereof to be tested in existing clinical populations and to guide future study to advance understanding and treatment of this heterogeneous disorder., (© 2019 Wiley Periodicals, Inc.)

Objective: Avoidant/restrictive food intake disorder (ARFID) and anorexia nervosa (AN) are restrictive eating disorders. There is a proposal before the American Psychiatric Association to broaden the current DSM-5 criteria for ARFID, which currently require dietary intake that is inadequate to support energy or nutritional needs. We compared the clinical presentations of ARFID and AN in an outpatient sample to determine how a more inclusive definition of ARFID, heterogeneous for age and weight status, is distinct from AN., Methods: As part of standard care, 138 individuals with AN or ARFID completed an online assessment battery and agreed to include their responses in research., Results: Individuals with ARFID were younger, reported earlier age of onset, and had higher percent median BMI (%mBMI) than those with AN (all ps < .001). Individuals with ARFID scored lower on measures of eating pathology, depression, anxiety, and clinical impairment (all ps < .05), but did not differ from those with AN on restrictive eating (p = .52), and scored higher on food neophobia (p < .001)., Discussion: Allowing psychosocial impairment to be sufficient for an ARFID diagnosis resulted in a clinical picture of ARFID such that %mBMI was higher (and in the normal range) compared with AN. Differences in gender distribution, age, and age of onset remained consistent with previous research. Both groups reported similar levels of dietary restriction, although ARFID can be distinguished by relatively higher levels of food neophobia. Currently available measures of eating pathology may capture certain ARFID symptoms, but highlight the need for measures of impairment relative to ARFID., (© 2018 Wiley Periodicals, Inc.)

The Eating Pathology Symptoms Inventory (EPSI) is a 45-item self-report measure of eating pathology designed to be sensitive in assessing symptoms among diverse populations of individuals with disordered eating. The current study represents the first external validation of the EPSI as well as the first to examine the factor structure in an outpatient eating disorder clinic sample. We conducted an exploratory factor analysis in three separate samples: an outpatient clinic sample (n = 284), a college sample (n = 296), and a community sample (n = 341) and compared the observed factor structures to the original 8-factor solution proposed by Forbush et al. (2013). We also investigated whether the subscales correlated with the Eating Disorder Examination Questionnaire (EDE-Q) and a clinical impairment measure among the outpatient clinic sample. Results suggested between 7 and 8 factors for each of the three samples. Our findings largely replicated those of the original EPSI development study, excepting some deviations in the Muscle Building, Cognitive Restraint, and Excessive Exercise subscales. However, confirmatory factor analysis and exploratory structural equation modeling produced poor model fit, which may be related to the item heterogeneity within many of the subscales. Finally, eating disorder attitudes and behaviors assessed by the EPSI were significantly correlated with the EDE-Q and with clinical impairment. Overall, our results highlight both strengths and limitations of the EPSI. Findings provide preliminary support for the use of the EPSI among research with diverse populations, and present several avenues for future research for enhancing clinical utility., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

There is an established relationship between increases in negative affect and engagement in binge eating and purging behaviors. Some evidence suggests that these behaviors may also be maintained via subsequent increases in positive affect. However, negative and positive affect are broad terms encompassing many emotions, and there is a theoretical speculation that every emotion consists of at least of three separate dimensions: valence, arousal, and approach/withdrawal. We conducted secondary analyses on a previously collected dataset using ecological momentary assessment in 133 women with bulimia nervosa. Participants rated their experience of discrete emotions and bulimic behaviors six times per day. Negative and positive emotions were organized within the 3-dimensional space characterized by valence, arousal, and approach/withdrawal. With multilevel modeling, we examined the trajectories of dimensionally defined emotion constructs prior and subsequent to bulimic behaviors as well as on days with and without bulimic behaviors. Negative valence, high arousal, and avoidance typified emotions that reached the highest levels before bulimic behaviors and were at the highest mean levels on days with bulimic behaviors. Arousal did not appear to moderate the trajectories of positive emotions. Application of a dimensional understanding of emotions may help elucidate the complex relationship between mood and disordered eating., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: Disordered eating attitudes and behaviors are prevalent among college women, and peers appear to influence current and future eating pathology. Social network analysis (SNA) is an innovative quantitative method to examine relationships (i.e., ties) among people based on their various attributes. In this study, the social network of one sorority was modeled using exponential random graph model (ERGM) to explore if homophily, or the tendency for relationship ties to exist based on shared attributes, was present according to sorority members' disordered eating behaviors/attitudes and their body mass index (BMI)., Method: Participants included members of one sorority at a large Southeastern university. All members were included on a roster unless they elected to opt out during the consent process, and 41 (19%) of the members completed the study measures. Participants completed the Social Network Questionnaire developed for this study (degree of "liking" of every member on the roster), the Eating Disorder Examination-Questionnaire (EDE-Q), and a demographics questionnaire in exchange for one hour of community service credit., Results: The final sample consisted of mostly White women with an average age of 20. Homophily across liking ties was examined based on the EDE-Q Global scale, episodes of binge eating, and BMI. The greater the difference in EDE-Q Global scores, the more likely the participants were to like one another. The greater the difference in BMI, the less likely the participants were to like one another. Binge eating was unrelated to homophily., Discussion: College sorority women appear to prefer other women with dissimilar levels of disordered eating attitudes, suggesting complex interactions between stigmatized or valued disordered eating attributes. Women with similar BMI were more likely to like one another, confirming past findings., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Beaker is a relatively new laboratory information system (LIS) offered by Epic Systems Corporation as part of its suite of health-care software and bundled with its electronic medical record, EpicCare. It is divided into two modules, Beaker anatomic pathology (Beaker AP) and Beaker Clinical Pathology. In this report, we describe our experience implementing Beaker AP version 2014 at an academic medical center with a go-live date of October 2015., Methods: This report covers preimplementation preparations and challenges beginning in September 2014, issues discovered soon after go-live in October 2015, and some post go-live optimizations using data from meetings, debriefings, and the project closure document., Results: We share specific issues that we encountered during implementation, including difficulties with the proposed frozen section workflow, developing a shared specimen source dictionary, and implementation of the standard Beaker workflow in large institution with trainees. We share specific strategies that we used to overcome these issues for a successful Beaker AP implementation. Several areas of the laboratory-required adaptation of the default Beaker build parameters to meet the needs of the workflow in a busy academic medical center. In a few areas, our laboratory was unable to use the Beaker functionality to support our workflow, and we have continued to use paper or have altered our workflow. In spite of several difficulties that required creative solutions before go-live, the implementation has been successful based on satisfaction surveys completed by pathologists and others who use the software. However, optimization of Beaker workflows has continued to be an ongoing process after go-live to the present time., Conclusions: The Beaker AP LIS can be successfully implemented at an academic medical center but requires significant forethought, creative adaptation, and continued shared management of the ongoing product by institutional and departmental information technology staff as well as laboratory managers to meet the needs of the laboratory., Competing Interests: There are no conflicts of interest.

Objective: Anxiety is a risk factor for disordered eating, but the mechanisms by which anxiety promotes disordered eating are poorly understood. One possibility is local versus global cognitive processing style, defined as a relative tendency to attend to details at the expense of the "big picture." Anxiety may narrow attention, in turn, enhancing local and/or compromising global processing. We examined relationships between global/local processing style, anxiety, and disordered eating behaviors in a transdiagnostic outpatient clinical sample. We hypothesized that local (vs. global) processing bias would mediate the relationship between anxiety and disordered eating behaviors., Method: Ninety-three participants completed the eating disorder examination-questionnaire (EDE-Q), State-Trait Anxiety Inventory (STAI)-trait subscale, and the Navon task (a test of processing style in which large letters are composed of smaller letters both congruent and incongruent with the large letter). The sample was predominantly female (95%) with a mean age of 27.4 years (SD = 12.1 years)., Results: Binge eating, but not fasting, purging, or excessive exercise, was correlated with lower levels of global processing style. There was a significant indirect effect between anxiety and binge eating via reduced global level global/local processing., Discussion: In individuals with disordered eating, being more generally anxious may encourage a detailed-oriented bias, preventing individuals from maintaining the bigger picture and making them more likely to engage in maladaptive behaviors (e.g., binge eating)., (© 2017 Wiley Periodicals, Inc.)

Objective: Adolescents and women with anorexia nervosa (AN) are known to severely restrict total calorie and fat intake. However, data are limited regarding specific macronutrient intake associated with weight gain in AN., Objective: To prospectively investigate dietary macronutrient composition associated with weight gain in adolescent girls with AN., Method: A prospective naturalistic study of 90 girls 12-18 years old; 45 with AN and 45 healthy normal-weight-controls over a 6-12-month period. Participants completed four-day food diaries and underwent body composition assessment using dual energy X-ray absorptiometry. Weight gain was defined as a ≥10% increase in body mass index (BMI) from baseline., Results: Baseline clinical characteristics did not differ between girls with AN who did not gain weight (AN-0) versus those who did (AN-1) over the following 6-12 month period except for percentage of calories from proteins (p = 0.046). At 6-12 month follow-up, AN-1 consumed a lower percentage of total calories from protein (p = .001), and a higher percentage of total calories from fat (p = .02) compared to AN-0. AN-1 had a significant increase in the percentage of total calories obtained from and poly-unsaturated-fatty acids (PUFA) (p = 0.006) compared to AN-0, between baseline and follow-up. Within the AN group, BMI at follow-up was associated positively with percentage of total calories obtained from fat, MUFA, and PUFA (p < .05) at 6/12 months, and inversely with the percentage of total calories obtained from carbohydrates and proteins (p = .03)., Discussion: Consuming a greater proportion of total calories from fat is associated with weight gain in adolescent girls with AN., (© 2017 Wiley Periodicals, Inc.)

Food restriction among individuals with anorexia nervosa (AN) is regarded as a goal-directed behavior. However, Walsh (2013) theorized that, although restriction is initially maintained by operant conditioning (with successful weight loss and external praise as salient rewards), it ultimately becomes a classically conditioned habit, persisting regardless of the presence of these once-salient rewards. Understanding food restriction as a well-ingrained habit may provide insight into treatment resistance. Further, it is not clear whether habitual food restriction is present among individuals with atypical AN (i.e. who engage in food restriction but are not low-weight). This study evaluated whether strength of habit predicted self-reported restriction above and beyond cognitive restraint. Seventy-eight individuals with AN or atypical AN completed the Eating Pathology Symptoms Inventory Restriction (EPSI-R) and Cognitive Restraint (EPSI-CR) subscales and the Self-Report Habit Index (SRHI) adapted for food restriction. We used a hierarchical multiple regression model to test whether habit strength predicted food restriction above and beyond cognitive restraint. After adding illness duration (step 1) and diagnosis (step 2) to the model, cognitive restraint (step 3) was not significant in explaining variation in restriction, whereas adding habit strength to the model (step 4) explained 27.9% of the variance in restriction (p<0.001). This is the first study to test a key component of Walsh's theory. Results provide support for food restriction maintenance through habit, rather than through effortful cognitive restraint. Because current models of AN characterize food restriction as purposeful, further research is needed to better understand habitual restriction in AN., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

We used the magnetic search coil technique to measure the horizontal cervico-ocular reflex (COR) of 8 subjects in response to transient or sinusoidal (0.1-1.0 Hz) trunk rotations while their heads were firmly immobilized. Although we were able to resolve eye rotations of < 0.05 degrees, the COR was hardly measurable (gain was always < 0.07). This finding, made with the most precise measurement technique used to date, suggests that the COR makes a negligible contribution to the stability of gaze in normal subjects during natural activities.