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ABSTRACT Objective Method Results Discussion Cognitive‐behavioral therapy for avoidant/restrictive food intake disorder (ARFID; CBT‐AR) shows promise in improving clinical outcomes in children/adolescents and adults. We aimed to identify predictors of outcomes in CBT‐AR. We hypothesized that younger age, non‐underweight status, and presence of the fear of aversive consequences profile of ARFID would predict greater likelihood of remission post–treatment, and that presence of the lack of interest in eating/food and sensory sensitivity profiles would predict greater likelihood of persistence post‐treatment. We included sex as an exploratory predictor.Individuals (N = 94, ages 10–55 years) were offered 20–30 outpatient sessions of CBT‐AR. We collected clinical and demographic data at pre‐treatment, and remission status at post‐treatment.Consistent with our hypothesis, presence (versus absence) of the fear profile predicted an almost three‐fold increased likelihood of remission. Presence of the sensory profile, lack of interest profile, age, weight status, and sex were not predictors of ARFID outcome.The fear of aversive consequences profile of ARFID may be more amenable to treatment with CBT‐AR. This is the first study to identify predictors of treatment outcome following CBT‐AR. Randomized controlled trials are needed to confirm these findings and examine moderators. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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). In this longitudinal study, the authors examined the course and outcomes of avoidant/restrictive food intake disorder (ARFID) in a sample of 100 youth aged 9 to 23 years over the course of 2 years. Across the 2-year follow-up period, half the sample persisted with their original diagnosis, and 3% of participants developed anorexia nervosa. Results indicate that profiles of greater sensory sensitivity to food and lack of interest in food/eating were associated with higher likelihood of ARFID persistence at year 1 only, whereas greater severity in the fear of aversive consequences of eating was associated with higher likelihood of ARFID remission at year 2 only. These findings highlight the persistence of ARFID and suggest that outcomes may vary depending on an individual's ARFID presentation. [ABSTRACT FROM AUTHOR]

Avoidant/restrictive food intake disorder (ARFID) is a feeding and eating disorder that is characterized by avoidant or restrictive eating not primarily motivated by body shape or weight concerns. We aimed to determine the frequency of ARFID symptoms and study its characteristics and associated gastrointestinal symptoms. We conducted a retrospective review of charts from 410 consecutive referrals (ages, 18–90 y; 73.0% female) to a tertiary care center for neurogastroenterology examination, from January through December 2016. Blinded coders (n = 4) applied Diagnostic and Statistical Manual of Mental Disorders, 5th edition, criteria for ARFID, with substantial diagnostic agreement (κ = 0.66). Twenty-six cases (6.3%) met the full criteria for ARFID and 71 cases (17.3%) had clinically significant avoidant or restrictive eating behaviors with insufficient information for a definitive diagnosis of ARFID. Of patients with ARFID symptoms (n = 97), 90 patients (92.8%) cited fear of gastrointestinal symptoms as motivation for their avoidant or restrictive eating. A series of binary logistic regressions showed that the likelihood of having ARFID symptoms increased significantly in patients with eating- or weight-related complaints (odds ratio [OR], 5.09; 95% CI, 2.54–10.21); with dyspepsia, nausea, or vomiting (OR, 3.59; 95% CI, 2.04–6.32); with abdominal pain (OR, 4.72; 95% CI, 1.87–11.81); or with lower GI diagnoses (OR, 2.40; 95% CI, 1.34-4.32). In a retrospective study of patients undergoing neurogastroenterology examinations, we found ARFID symptoms to be related most frequently to fear of gastrointestinal symptoms. Patients undergoing neurogastroenterology or motility examinations should be evaluated for symptoms of ARFID, particularly when providers consider dietary interventions. [ABSTRACT FROM AUTHOR]

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. Plain English Summary: Avoidant/restrictive food intake disorder (ARFID) is a feeding/eating disorder characterized by avoidance/restriction of food intake by volume and/or variety. In contrast to other eating disorders (e.g., anorexia nervosa, bulimia nervosa), dietary restriction in ARFID is not motivated by shape and weight concerns. Instead, it is driven by sensory sensitivities, fear of aversive consequences, and lack of interest in food/eating. The emergence of other eating disorder symptoms - such as shape and weight concerns - in the longitudinal course of ARFID is an important clinical phenomenon that is neither robustly documented nor well understood. Following ARFID history, 71% of participants in our study developed a restricting eating disorder and 29% developed a binge-spectrum eating disorder. Cognitive symptoms of other eating disorders (e.g., shape/weight concerns) onset prior to behavioral symptoms (e.g., food avoidance). Diagnostic crossover from ARFID to another eating disorder following the development of shape/weight concerns represents an interesting and important clinical phenomenon. Our findings suggest potential pathways by which ARFID may lead to the development of a subsequent eating disorder, in turn highlighting critical targets that may be intervened on to prevent this trajectory. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose Of Review: The neurohormone oxytocin (OXT) impacts food intake as well as cognitive, emotional, and social functioning-all of which are central to eating disorder (ED) pathology across the weight spectrum. Here, we review findings on endogenous OXT levels and their relationship to ED pathology, the impact of exogenous OXT on mechanisms that drive ED presentation and chronicity, and the potential role of genetic predispositions in the OXT-ED link.Recent Findings: Current findings suggest a role of the OXT system in the pathophysiology of anorexia nervosa. In individuals with bulimia nervosa, endogenous OXT levels were comparable to those of healthy controls, and exogenous OXT reduced food intake. Studies in other ED are lacking. However, genetic studies suggest a broad role of the OXT system in influencing ED pathology. Highlighting findings on why OXT represents a potential biomarker of and treatment target for ED, we advocate for a systematic research approach spanning the entire ED spectrum. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Anorexia nervosa is associated with low bone mineral density (BMD) and deficits in bone microarchitecture and strength. Low BMD is common in atypical anorexia nervosa, in which criteria for anorexia nervosa are met except for low weight. We investigated whether women with atypical anorexia nervosa have deficits in bone microarchitecture and estimated strength at the peripheral skeleton. Method: Measures of BMD and microarchitecture were obtained in 28 women with atypical anorexia nervosa and 27 controls, aged 21–46 years. Results: Mean tibial volumetric BMD, cortical thickness, and failure load were lower, and radial trabecular number and separation impaired, in atypical anorexia nervosa versus controls (p <.05). Adjusting for weight, deficits in tibial cortical bone variables persisted (p <.05). Women with atypical anorexia nervosa and amenorrhea had lower volumetric BMD and deficits in microarchitecture and failure load versus those with eumenorrhea and controls. Those with a history of overweight/obesity or fracture had deficits in bone microarchitecture versus controls. Tibial deficits were particularly marked. Less lean mass and longer disease duration were associated with deficits in high‐resolution peripheral quantitative computed tomography (HR‐pQCT) variables in atypical anorexia nervosa. Discussion: Women with atypical anorexia nervosa have lower volumetric BMD and deficits in bone microarchitecture and strength at the peripheral skeleton versus controls, independent of weight, and particularly at the tibia. Women with atypical anorexia nervosa and amenorrhea, less lean mass, longer disease duration, history of overweight/obesity, or fracture history may be at higher risk. This is salient as deficits in HR‐pQCT variables are associated with increased fracture risk. Public Significance: Atypical anorexia nervosa is a psychiatric disorder in which psychological criteria for anorexia nervosa are met despite weight being in the normal range. We demonstrate that despite weight in the normal range, women with atypical anorexia nervosa have impaired bone density, structure, and strength compared to healthy controls. Whether this translates to an increased risk of incident fracture in this population requires further investigation. [ABSTRACT FROM AUTHOR]

A correction to the article "Impact of low-weight severity and menstrual status on bone in adolescent girls with anorexia nervosa" that was published in the April 2017 issue is presented.

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. Plain English Summary: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Secretive eating, characterized by eating privately to conceal being seen, may reflect eating- and/or body-related shame, be associated with depression, and correlate with binge eating, which predicts weight gain and eating disorder onset. Increasing understanding of secretive eating in youth may improve weight status and reduce eating disorder risk. This study evaluated the prevalence and correlates of secretive eating in youth with overweight or obesity.Methods: Youth (N = 577) presented to five research/clinical institutions. Using a cross-sectional design, secretive eating was evaluated in relation to eating-related and general psychopathology via linear and logistic regression analyses.Results: Secretive eating was endorsed by 111 youth, who were, on average, older than youth who denied secretive eating (mean age = 12.07 ± 2.83 versus 10.97 ± 2.31). Controlling for study site and age, youth who endorsed secretive eating had higher eating-related psychopathology and were more likely to endorse loss of control eating and purging than their counterparts who did not endorse secretive eating. Groups did not differ in excessive exercise or behavioral problems. Dietary restraint and purging were elevated among adolescents (≥13y) but not children (<13y) who endorsed secretive eating; depression was elevated among children, but not adolescents, who endorsed secretive eating.Conclusions: Secretive eating may portend heightened risk for eating disorders, and correlates of secretive eating may differ across pediatric development. Screening for secretive eating may inform identification of problematic eating behaviors, and understanding factors motivating secretive eating may improve intervention tailoring. [ABSTRACT FROM AUTHOR]

Background: Exclusion diets for gastrointestinal symptom management have been hypothesized to be a risk factor for avoidant/restrictive food intake disorder (ARFID; a non‐body image‐based eating disorder). In a retrospective study of pediatric and adult neurogastroenterology patients, we aimed to (1) identify the prevalence and characteristics of an exclusion diet history and (2) evaluate if an exclusion diet history was concurrently associated with the presence of ARFID symptoms. Methods: We conducted a chart review of 539 consecutive referrals (ages 6–90, 69% female) to adult (n = 410; January–December 2016) and pediatric (n = 129; January 2016–December 2018) neurogastroenterology clinics. Masked coders (n = 4) retrospectively applied DSM‐5 criteria for ARFID and a separate coder assessed documentation of exclusion diet history. We excluded patients with no documentation of diet in the chart (n = 35) or who were not orally fed (n = 9). Results: Of 495 patients included, 194 (39%) had an exclusion diet history, and 118 (24%) had symptoms of ARFID. Of reported diets, dairy‐free was the most frequent (45%), followed by gluten‐free (36%). Where documented, exclusion diets were self‐initiated by patients/parents in 66% of cases, and recommended by gastroenterology providers in 30%. Exclusion diet history was significantly associated with the presence of ARFID symptoms (OR = 3.12[95% CI 1.92–5.14], p < 0.001). Conclusions: History of following an exclusion diet was common and was most often patient‐initiated among pediatric and adult neurogastroenterology patients. As patients with self‐reported exclusion diet history were over three times as likely to have ARFID symptoms, providers should be cognizant of this potential association when considering dietary interventions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Avoidant/restrictive food intake disorder (ARFID) is a feeding and eating disorder for which there are very few evidence-based treatments. Cognitive-Behavioral Therapy for Avoidant/Restrictive Food Intake Disorder (CBT-AR) is a novel exposure-based treatment which is suitable for people aged ten and older. The primary aims of the study are to undertake a real-world evaluation of the feasibility, acceptability, and preliminary effectiveness of CBT-AR for young people aged 12–25 years old in an outpatient eating disorders service where the patient population has high levels of psychiatric comorbidity. Clinicians, patients, and parents/guardians will be involved in the evaluation. Assessments will be carried out at baseline, during weekly sessions, at the end of each treatment stage, at end of CBT-AR treatment, and at 3-month follow-up. Assessments will measure ARFID symptoms, mood, quality of life, therapeutic alliance, and feedback on the treatment. The study will take place over a 12-month period and will evaluate the use of CBT-AR within real-life clinical practice conditions, noting how and why deviations from the treatment have occurred. The findings of this research will inform future ARFID treatment delivery and the implementation of CBT-AR at outpatient mental health services. [ABSTRACT FROM AUTHOR]

Objective: There are limited data to guide the interpretation of scores on measures of eating‐disorder psychopathology among underrepresented individuals. We aimed to provide norms for the Eating Disorder Examination–Questionnaire (EDE‐Q) and Clinical Impairment Assessment (CIA) across racial/ethnic, gender, and sexual identities, and sexual orientations and their intersections by recruiting a diverse sample of Amazon MTurk workers (MTurkers; N = 1782). Method: We created a comprehensive, quantitative assessment of racial/ethnic identification, gender identification, sex assigned at birth, current sexual identification, and sexual orientation called the Demographic Assessment of Racial, Sexual, and Gender Identities (DARSGI). We calculated normative data for each demographic category response option. Results: Our sample was comprised of 68% underrepresented racial/ethnic identities, 42% underrepresented gender identities, 13% underrepresented sexes, and 49% underrepresented sexual orientations. We reported means and standard deviations for each demographic category response option and, where possible, mean estimates by percentile across intersectional groups. EDE‐Q Global Score for a subset of identities and intersections in the current study were higher than previously reported norms for those identities/intersections. Discussion: This is the most thorough reporting of norms for the EDE‐Q and CIA among racial/ethnic, sexual, and gender identities, and sexual orientations and the first reporting on multiple intersections, filling some of the gaps for commonly used measures of eating‐disorder psychopathology. These norms may be used to contextualize eating‐disorder psychopathology reported by underrepresented individuals. The data from the current study may help inform research on the prevention and treatment of eating‐disorder psychopathology in underrepresented groups. Public Significance: We provide the most thorough reporting on racial/ethnic, sexual, and gender identities, and sexual orientations for the Eating Disorder Examination – Questionnaire and Clinical Impairment Assessment, and the first reporting on intersections, which fills some of the gaps for commonly used measures of eating‐disorder psychopathology. These norms help inform research on the prevention and treatment of eating‐disorder psychopathology in underrepresented groups. [ABSTRACT FROM AUTHOR]

Objective: Anorexia nervosa is complicated by high bone resorption, low bo ne mineral density (BMD), and increased fracture risk. We investigated whether off-label antiresorptive therapy with denosumab increases BMD in women with anorexia nervosa. Design: Twelve-month, randomized, double-blind, placebo-controlled study. Methods: Thirty ambulatory women with anorexia nervosa and areal BMD (aB MD) T-score <-1.0 at =1 sites were randomized to 12 months of denosumab (60 mg subcutaneously q6 m onths)(n = 20) or placebo (n = 10). Primary end point was postero-anterior (PA) lumbar spine aBMD by dual-e nergy x-ray absorptiometry. Secondary end points included femoral neck aBMD, tibia and radius volumetric BMD and bone microarchitecture by high-resolution peripheral quantitative CT, tibia and radius failure load by fin ite element analysis (FEA), and markers of bone turnover. Results: Baseline mean (±s.d.) age (29 ± 8 (denosumab) vs 29 ± 7 years (placebo)), BMI (19.0 ± 1.7 vs 18.0 ± 2.0 kg/m2), and aBMD (PA spine Z-score -1.6±1.1 vs -1.7±1.4) were similar between groups. PA lumbar spine aBMD increase d in the denosumab vs placebo group over 12 months (P = 0.009). The mean (95% CI) increase in PA lumbar spine aBMD was 5.5 (3.8-7.2)% in the denosumab group and 2.2 (-0.3-4.7)% in the placebo group. The change in femoral neck aBMD was similar between groups. Radial trabecular number incre ased, radial trabecular separation decreased, and tibial cortical porosity decreased in the denosumab vs placebo group (P = 0.006). Serum C-terminal telopeptide of type I collagen and procollagen type I N-terminal propeptide decreas ed in the denosumab vs placebo group (P < 0.0001). Denosumab was well tolerated. Conclusions: Twelve months of antiresorptive therapy with denosumab reduced bone turnover and increased spine aBMD, the skeletal site most severely affected in women with ano rexia nervosa. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In adults, low-weight restrictive eating disorders, including anorexia nervosa (AN), are marked by chronicity and diagnostic crossover from restricting to binge-eating/purging. Less is known about the naturalistic course of these eating disorders in adolescents, particularly atypical AN (atyp-AN) and avoidant/restrictive food intake disorder (ARFID). To inform nosology of low-weight restrictive eating disorders in adolescents, we examined outcomes including persistence, crossover, and recovery in an 18-month observational study. We assessed 82 women (ages 10–23 years) with low-weight eating disorders including AN (n = 40; 29 restricting, 11 binge-eating/purging), atyp-AN (n = 26; 19 restricting, seven binge-eating/purging), and ARFID (n = 16) at baseline, nine months (9 M; 75% retention), and 18 months (18 M; 73% retention) via semi-structured interviews. First-order Markov modeling was used to determine diagnostic persistence, crossover, and recovery occurring at 9 M or 18 M. Among all diagnoses, the likelihood of remaining stable within a given diagnosis was greater than that of transitioning, with the greatest probability among ARFID (0.84) and AN-R (0.62). Persistence of BP and atypical presentations at follow-up periods was less stable (AN-BP probability 0.40; atyp-AN-R probability 0.48; atyp-AN-BP probability, 0.50). Crossover from binge-eating/purging to restricting occurred 72% of the time; crossover from restricting to binge-eating/purging occurred 23% of the time. The likelihood of stable recovery (e.g., recovery at both 9 M and 18 M) was between 0.00 and 0.36. Across groups, intake diagnosis persisted in about two-thirds, and recovery was infrequent, underscoring the urgent need for innovative treatment approaches to these illnesses. Frequent crossover between AN and atyp-AN supports continuity between typical and atypical presentations, whereas no crossover to ARFID supports its distinction. [ABSTRACT FROM AUTHOR]

Objective: Anorexia nervosa (AN) is a serious condition characterized by undernutrition, complicated by endocrine dysregulation, and with few predictors of recovery. Urinary free cortisol (UFC) is a predictor of weight gain, but 24‐h urine samples are challenging to collect. We hypothesized that serum dehydroepiandrosterone sulfate (DHEAS), which like cortisol is regulated by adrenocorticotropic hormone (ACTH), would predict weight gain and increases in fat mass in women with AN. Methods: We prospectively studied 34 women with AN and atypical AN, mean age 27.4 ± 7.7 years (mean ± SD), who received placebo in a 6‐month randomized trial. Baseline DHEAS and 24‐h UFC were measured by liquid chromatography with tandem mass spectrometry. Body composition was assessed at baseline and 6 months by DXA and cross‐sectional abdominal CT at L4. Results: Mean baseline DHEAS level was 173 ± 70 μg/dl (0.7 ± 0.3 times the mean normal range for age) and mean baseline UFC (n = 15) was 20 ± 18 μg/24 h (normal: 0–50 μg/24 h). Higher DHEAS levels predicted weight gain over 6 months (r = 0.61, p <.001). DHEAS levels also predicted increases in fat mass (r = 0.40, p =.03), appendicular lean mass (r = 0.38, p =.04), and abdominal adipose tissue (r = 0.60, p <.001). All associations remained significant after controlling for age, baseline BMI, OCP use, duration of AN, and SSRI/SNRI use. DHEAS levels correlated with UFC (r = 0.61, p =.02). Discussion: In women with AN, higher serum DHEAS predicts weight gain and increases in fat and muscle mass. Additional studies are needed to confirm these findings and further elucidate the association between DHEAS and weight gain. Public Significance: Anorexia nervosa is a severe psychiatric condition, and predictors of weight recovery are needed to improve prognostication and guide therapeutic decision making. While urinary cortisol is a predictor of weight gain, 24‐h urine collections are challenging to obtain. Like cortisol, dehydroepiandrosterone sulfate (DHEAS) is a hormone produced by the adrenal glands. As a readily available blood test, DHEAS holds promise as more practical biomarker of weight gain in anorexia nervosa. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. • Appetite regulating hormones following a test meal were investigated among individuals with ARFID and healthy controls • Latent growth curve model analyses revealed a different ghrelin trajectory following a meal in ARFID versus healthy controls • Ghrelin dysregulation may play a role in the maintenance of ARFID [ABSTRACT FROM AUTHOR]

Promoting representation of historically marginalized racial and ethnic populations in the eating disorders (EDs) field among professionals and the populations studied and served has long been discussed, with limited progress. This may be due to a reinforcing feedback loop in which individuals from dominant cultures conduct research and deliver treatment, participate in research, and receive diagnoses and treatment. This insularity maintains underrepresentation: EDs in historically marginalized populations are understudied, undetected, and undertreated. An Early Career Investigators Workshop generated recommendations for change that were not inherently novel but made apparent that accountability is missing. This paper serves as a call to action to spearhead a paradigm shift from equality to equity in the ED field. We provide a theoretical framework, suggest ways to disrupt the feedback loop, and summarize actionable steps to increase accountability in ED leadership and research toward enhancing racial/ethnic justice, equity, diversity, and inclusion (JEDI). These actionable steps are outlined in the service of challenging our field to reflect the diversity of our global community. We must develop and implement measurable metrics to assess our progress toward increasing diversity of underrepresented racial/ethnic groups and to address JEDI issues in our providers, patients, and research participants. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

Highlights • Oligo-amenorrrheic athletes have greater eating disorder pathology than controls. • Estrogen replacement improves drive for thinness and body dissatisfaction scores. • Administration of transdermal estradiol (vs. the pill) reduces uncontrolled eating. Abstract Objective Estrogen replacement prevents worsening body dissatisfaction with weight gain in adolescents with anorexia nervosa. However, the impact of estrogen administration on eating disorder (ED) pathology in normal-weight young women with exercise-induced amenorrhea is unknown. We hypothesized that (1) normal-weight oligo-amenorrheic athletes (OA) would show greater ED pathology than eumenorrheic athletes (EA) and non-athletes (NA), and (2) 12 months of estrogen replacement would improve those symptoms. Trial design Randomized trial. Methods One hundred seventeen OA, 50 EA, and 41 NA completed the Eating Disorder Inventory-2 (EDI-2) for measures of Drive for Thinness (DT) and Body Dissatisfaction (BD) and the Three-Factor Eating Questionnaire-R18 (TFEQ-R18). OA were then randomized to receive 100 mcg transdermal 17β-estradiol with cyclic progesterone (PATCH), an oral contraceptive pill (30 mcg ethinyl estradiol + 0.15 mg desogestrel) (PILL), or no estrogen (E-) for 12 months. Data are reported for the subset that completed questionnaires at 0 and 12 months between 11/2009 and 10/2016. Results OA showed higher EDI-2 DT and TFEQ-R18 Cognitive Restraint scores than EA and NA and higher EDI-2 BD scores than EA. Over 12 months, the E+ group (PATCH+PILL), compared to E-, showed improved trajectories for EDI-2 DT and BD scores. In 3-group comparisons, PATCH outperformed E- for decreases in EDI-2 DT and BD, and the PILL for TFEQ-R18 Uncontrolled Eating. Conclusion In OA, 12 months of estrogen replacement improves ED pathology trajectories, emphasizing the broad importance of normalizing estrogen levels. Clinical Trial Registration ClinicalTrials.gov identifier: NCT00946192. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Fear and disgust are distinct emotions that have been independently linked with EDs and may motivate avoidance behaviors that may be relevant targets for ED interventions (e.g., food rejection). Despite similar motivational function, it is possible that one emotion is more strongly associated with ED symptoms, relative to the other. Given that emerging evidence suggests that disgust-based behavior may be more difficult to change than fear-based behaviors, research is needed to evaluate whether each emotion differentially relates to ED symptoms. Therefore, the current study tested the relative importance of fear and disgust in accounting for variance in ED symptoms. Participants included undergraduate men (n = 127) and women (n = 263) from a university in the northeast US. Participants completed self-report measures assessing demographics, disordered eating attitudes and behaviors, and visual analog scales assessing fear and disgust responses to high-calorie food images, low-calorie food images, and non-food fear and disgust images. Bivariate correlations revealed significant positive associations among fear, disgust, and EDE-Q global symptom scores. Relative weights analysis results yielded relative importance weights that suggested disgust responding to high calorie food images accounts for the greatest total variance in EDE-Q global symptom scores in men, and fear responding to high calorie food images accounts for the greatest total variance in EDE-Q scores in women. Findings provide initial evidence that investigative and clinical efforts should consider fear and disgust as unique facets of negative affect with different patterns of relative importance to ED symptoms in undergraduate men and women. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to investigate predictors of long-term recovery from eating disorders 22 years after entry into a longitudinal study. Method One hundred and seventy-six of the 228 surviving participants (77.2%) were re-interviewed 20-25 years after study entry using the Longitudinal Interval Follow-up Evaluation to assess ED recovery. The sample consisted of 100 women diagnosed with anorexia nervosa (AN) and 76 with bulimia nervosa (BN) at study entry. Results A comorbid diagnosis of major depression at the start of the study strongly predicted having a diagnosis of AN-Restricting type at the 22-year assessment. A higher body mass index (BMI) at study intake decreased the odds of being diagnosed with AN-Binge Purge type, relative to being recovered, 22 years later. The only predictor that increased the likelihood of having a diagnosis of BN at the 22-year assessment was the length of time during the study when the diagnostic criteria for BN were met. Conclusions Together, these results indicate that the presence and persistence of binge eating and purging behaviors were poor prognostic indicators and that comorbidity with depression is particularly pernicious in AN. Treatment providers might pay particular attention to these issues in an effort to positively influence recovery over the long-term. [ABSTRACT FROM AUTHOR]

The hypothalamic hormone oxytocin (OXT) plays an important role in a range of physiological processes and social-emotional functioning in both sexes. In women, physiological stimuli, such as suckling and parturition, result in pulsatile release of OXT into the peripheral circulation via the posterior pituitary gland. However, data regarding OXT secretory patterns in men during a state of rest are limited. Further, the relationship between secretory dynamics of OXT and emotional measures has never been evaluated. We hypothesized a pulsatile pattern of OXT secretion in men, and explored the relationship between OXT secretory patterns and social-emotional functioning. Methods Deconvolution analysis was performed on serum OXT levels obtained every 5 min over a period of 10 h in 5 healthy normal weight men. Area under the curve (AUC), average OXT values, and pulse characteristics [pulse number, inter-pulse interval, pulse height and mass (area under each pulse)] were calculated. State Adult Attachment Measure (SAAM) assessed types of human attachment. Interpersonal Support Evaluation List (ISEL) assessed perception of social support. Toronto Alexithymia Scale (TAS-20) measured the ability to express and identify one’s own emotions. Results Mean age was 22.8 ± 1.2 years, and BMI was 21.7 ± 0.4 kg/m 2 (mean ± SEM). Assuming a basal secretion of zero and a half life of five to seven minutes, we demonstrated the following: OXT AUC: 5421 ± 1331 pg/ml, mean OXT level: 9.1 pg/ml, mean pulse number: 22 ± 3/10hr, mean pulse height: 1.81 ± 0.48 pg/ml, mean pulse mass: 30.34 ± 10.29 pg/ml and mean inter-pulse interval: 27 ± 4 min. The SAAM Avoidant scale correlated negatively with mean OXT pulse height (r = −0.90, p = 0.04) and pulse mass (r = −0.95, p = 0.01). The ISEL Belonging score correlated positively with OXT AUC (r = 0.89, p = 0.04) and average OXT (r = 0.93, p = 0.02). ISEL Appraisal score also had a positive association with mean OXT pulse height (r = 0.99, p = 0.0006) and pulse mass (r = 0.98, p = 0.003). Finally, ISEL total score had a significant correlation with average OXT values (r = 0.90, p = 0.04). While none of the subjects had a score in the alexithymia range, TAS-20 Difficulty describing feelings score had an inverse correlation with OXT pulse height (r = −0.96, p = 0.01) and pulse mass (r = −0.99, p = 0.001). TAS-20 total score also had an inverse correlation with OXT pulse height (r = −0.94, p = 0.02) and pulse mass (r = −0.96, p = 0.009). Conclusion We demonstrate a pulsatile pattern of peripheral OXT secretion in healthy men at rest. Subjects with lower OXT pulse height and pulse mass had a more avoidant style of attachment, felt less supported, and expressed greater difficulty in describing their feelings. Our findings support the concept that OXT is a key mediator of social-emotional functioning. Future studies to determine causality are warranted. [ABSTRACT FROM AUTHOR]

Network analysis has recently been introduced as a clinically relevant methodology for understanding the structure of mental disorders and for evaluating cognitive behavioral models of psychopathology. The current study uses network analysis to validate the transdiagnostic model of eating disorders by examining the association between overvaluation of shape and weight and eating disorder symptoms. Eating disorder symptoms were measured among a sample of 194 treatment-seeking children, adolescents, and adults presenting to an outpatient eating disorder clinic. We created transdiagnostic and disorder-specific symptom networks and assessed symptom strength and connectivity. Congruent with the transdiagnostic model, overvaluation of weight and shape emerged among the strongest symptoms in the network, and global network connectivity was higher among individuals with high overvaluation when compared to individuals with low overvaluation. An exploratory analysis revealed that overvaluation of weight and shape was central to anorexia nervosa, bulimia nervosa, and binge eating disorder. Results highlight the associative strength of overvaluation of shape and weight with eating disorder symptoms, regardless of the specific eating disorder diagnosis. Our findings corroborate overvaluation of weight and shape as a transdiagnostic treatment target and potentially useful severity specifier for binge eating disorder. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Obesity affects more than one-third of adults in the U.S., and effective treatment options are urgently needed. Oxytocin administration induces weight loss in animal models of obesity via effects on caloric intake, energy expenditure, and fat metabolism. We study intranasal oxytocin, an investigational drug shown to reduce caloric intake in humans, as a potential novel treatment for obesity. We report the rationale, design, methods, and biostatistical analysis plan of a randomized, double-blind, placebo-controlled clinical trial of intranasal oxytocin for weight loss (primary endpoint) in adults with obesity. Participants (aged 18–45 years) were randomly allocated (1:1) to oxytocin (four times daily over eight weeks) versus placebo. Randomization was stratified by biological sex and BMI (30 to <35, 35 to <40, ≥40 kg/m2). We investigate the efficacy, safety, and mechanisms of oxytocin administration in reducing body weight. Secondary endpoints include changes in resting energy expenditure, body composition, caloric intake, metabolic profile, and brain activation via functional magnetic resonance imaging in response to food images and during an impulse control task. Safety and tolerability (e.g., review of adverse events, vital signs, electrocardiogram, comprehensive metabolic panel) are assessed throughout the study and six weeks after treatment completion. Sixty-one male and female participants aged 18–45 years were randomized (mean age 34 years, mean BMI 37 kg/m2). The study sample is diverse with 38% identifying as non-White and 20% Hispanic. Investigating intranasal oxytocin's efficacy, safety, and mechanisms as an anti-obesity medication will advance the search for optimal treatment strategies for obesity and its associated severe sequelae. [ABSTRACT FROM AUTHOR]

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. • Low-weight ARFID females are as undernourished as those with anorexia nervosa (AN). • Low-weight ARFID showed lower levels of total ghrelin around a meal than AN. • Low-weight ARFID did not differ from AN or healthy controls (HC) in PYY levels. • Low-weight ARFID did not show sustained high PYY levels post-meal. • Hormone differences may differentiate low-weight ARFID and AN. [ABSTRACT FROM AUTHOR]

• Developmental stage-dependent associations between ghrelin and white-matter in AN. • No relationship between ghrelin and white-matter in healthy individuals, only in patients. • Higher level of ghrelin associated with lower white-matter microstructure in the fornix in AN. 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. 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). 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. 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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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 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. [ABSTRACT FROM AUTHOR]

Background: Appetite-regulating hormones are implicated in anorexia nervosa (AN) pathophysiology, however, data are limited for appetite-regulating hormones across the AN weight spectrum. We aimed to investigate fasting and post-prandial concentrations of appetite-regulating hormones - peptide YY (PYY), cholecystokinin (CCK), and ghrelin - among adolescent and young adult females across the AN weight spectrum, specifically those with AN and Atypical AN, and healthy controls (HC)., Methods: Participants (N = 95; ages 11-22 years) included 33 with AN, 25 with Atypical AN, and 37 HC. AN was differentiated from Atypical AN by BMI < 10th percentile for age and sex (if <18 years) or < 18.5 kg/m 2 (if ≥18 years). Blood samples were collected fasting and 30, 60 and 120 minutes following a standardized meal to assess total PYY, CCK, and total ghrelin concentrations., Results: Median fasting and post-prandial PYY concentrations were significantly higher in AN vs. HC with medium differences (p = .001-.006, r = .34-.43). Atypical AN had significantly higher PYY concentrations compared to HC at T-0 (p = .027, r = .29) only, and did not significantly differ from concentrations in AN (p = .105-.413, r = .11-.22). Area under the curve (AUC; p = .001; r = .41) and peak PYY concentrations (p = .003; r = .41) were also significantly higher in AN vs. HC with medium differences. There were no significant differences in fasting (p = .885) or post-prandial (p = .846-.993) CCK concentrations across groups. AN and Atypical AN each had significantly higher ghrelin concentrations than HC with small to medium effect (AN vs HC p = .004-.025, r = .27-.36; Atypical AN vs HC p = .004-.033; r = .28-.28)., Conclusions: Higher peak postprandial concentrations of anorexigenic PYY in AN (compared to HC) may facilitate dietary restriction and contribute to maintenance of lower weight. Lack of CCK suppression in AN is maladaptive in the context of undernutrition. Despite continued restriction, ghrelin is adaptively higher in AN overall and may not be differentiated by weight status., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships Dr. Lawson receives grant support and research study drug from Tonix Pharmaceuticals. Dr. Lawson and/or immediate family member holds stock in Thermo Fisher Scientific, Zoetis, Danaher Corporation, Intuitive Surgical, Merck and West Pharmaceutical Services. Dr. Lawson is an inventor on US provisional patent application no. 63/467,980 (Oxytocin-based therapeutics to improve cognitive control in individuals with attention deficit hyperactivity disorder). Dr. Misra has consulted for Regeneron and Kyss Pharmaceuticals, receives study drug donation from Tonix Pharmaceuticals. Drs. Lawson and Misra receive royalties from UpToDate. Dr. Breithaupt is a consultant and on the scientific advisory board for Otsuka Pharma. Drs. Eddy and Thomas 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. Eddy and Thomas receive consulting fees from Equip Health. Dr. Becker, Dr. Eddy and Dr. Thomas receive royalties from Cambridge University Press for their book The Picky Eater’s Recovery Book: Overcoming Avoidant/Restrictive Food Intake Disorder. Drs. Burton-Murray and Thomas receive royalties from Oxford University Press for the sale of their book Cognitive-Behavioral Therapy for Rumination Syndrome. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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.

Background: Accumulating preclinical and preliminary translational evidence shows that the hypothalamic peptide oxytocin reduces food intake, increases energy expenditure, and promotes weight loss. It is currently unknown whether oxytocin administration is effective in treating human obesity., Methods: In this randomized, double-blind, placebo-controlled trial, we randomly assigned adults with obesity 1:1 (stratified by sex and obesity class) to receive intranasal oxytocin (24 IU) or placebo four times daily for 8 weeks. The primary end point was change in body weight (kg) from baseline to week 8. Key secondary end points included change in body composition (total fat mass [g], abdominal visceral adipose tissue [cm 2 ], and liver fat fraction [proportion; range, 0 to 1; higher values indicate a higher proportion of fat]), and resting energy expenditure (kcal/day; adjusted for lean mass) from baseline to week 8 and caloric intake (kcal) at an experimental test meal from baseline to week 6., Results: Sixty-one participants (54% women; mean age ± standard deviation, 33.6 ± 6.2 years; body-mass index [the weight in kilograms divided by the square of the height in meters], 36.9 ± 4.9) were randomly assigned. There was no difference in body weight change from baseline to week 8 between oxytocin and placebo groups (0.20 vs. 0.26 kg; P=0.934). Oxytocin (vs. placebo) was not associated with beneficial effects on body composition or resting energy expenditure from baseline to week 8 (total fat: difference [95% confidence interval], 196.0 g [-1036 to 1428]; visceral fat: 3.1 cm 2 [-11.0 to 17.2]; liver fat: -0.01 [-0.03 to 0.01]; resting energy expenditure: -64.0 kcal/day [-129.3 to 1.4]). Oxytocin compared with placebo was associated with reduced caloric intake at the test meal (-31.4 vs. 120.6 kcal; difference [95% confidence interval], -152.0 kcal [-302.3 to -1.7]). There were no serious adverse events. Incidence and severity of adverse events did not differ between groups., Conclusions: In this randomized, placebo-controlled trial in adults with obesity, intranasal oxytocin administered four times daily for 8 weeks did not reduce body weight. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov number, NCT03043053.).

Our objective was to characterize bone outcomes in adolescent and young adult women with atypical anorexia nervosa (AAN) compared to typical AN and normal-weight healthy controls (HC) based on DSM-5 criteria. Four hundred thirty-two participants (141 AN, 131 AAN and 160 HC), ages 12-21 years, underwent dual-energy X-ray absorptiometry for areal BMD, and a subset had high-resolution peripheral quantitative CT assessment of the distal radius and tibia for volumetric BMD (vBMD), bone geometry and microarchitecture, and microfinite element analysis for estimated strength. The groups did not differ for age, pubertal stage, menarcheal age or physical activity. BMI and bone outcomes overall were intermediate in AAN compared with AN and HC. This applied to spine, total hip and femoral neck BMD measures and many distal tibial measures. However, the mean whole-body less head BMD Z-score did not differ between AAN and AN, and it was lower in both vs. HC. Similarly, many distal radius measures did not differ between AAN vs. AN or HC but were lower in AN than HC. Lower BMI, lean mass and bone age, older menarcheal age and longer illness duration correlated with greater impairment of bone outcomes. These data indicate that individuals with AAN overall have bone outcomes that are intermediate between AN and HC.

Proteomics provides an opportunity for detection and monitoring of anorexia nervosa (AN) and its related variant, atypical-AN (atyp-AN). However, research to date has been limited by the small number of proteins explored, exclusive focus on adults with AN, and lack of replication across studies. This study performed Olink Proseek Multiplex profiling of 92 proteins involved in inflammation among females with AN and atyp-AN (N = 64), all < 90% of expected body weight, and age-matched healthy controls (HC; N=44). After correction for multiple testing, nine proteins differed significantly in the AN/atyp-AN group relative to HC group ( lower levels: CXCL1, HGF, IL-18R1, TNFSF14, TRANCE; higher levels: CCL23, Flt3L, LIF-R, MMP-1). The expression levels of three proteins ( lower IL-18R1, TRANCE; higher LIF-R) were uniquely disrupted in females with AN. No unique expression levels emerged for atyp-AN. Across the whole sample, twenty-one proteins correlated positively with BMI (ADA, AXIN1, CD5, CD244, CD40, CD6, CXCL1, FGF-21, HGF, IL-10RB, IL-12B, IL18, IL-18R1, IL6, LAP TGF-beta-1, SIRT2, STAMBP, TNFRSF9, TNFSF14, TRAIL, TRANCE) and six (CCL11, CCL23, FGF-19, IL8, LIF-R, OPG) were negatively correlated with BMI. Overall, our results replicate the prior study demonstrating a dysregulated inflammatory status in AN, and extend these results to atyp-AN (AN/atyp-AN all < 90% of expected body weight). Of the 27 proteins correlated with BMI, 18 were replicated from a prior study using similar methods, highlighting the promise of inflammatory protein expression levels as biomarkers of disease monitoring. Additional studies of individuals across the entire weight spectrum are needed to understand the role of inflammation in atyp-AN.