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Identified problems with the classification system of eating disorders (EDs), including its imperfect application to clinical samples, challenge its validity and limit its utility. The present study aimed to empirically identify and validate ED phenotypes in a multisite clinical sample using latent profile analysis (LPA). ED symptom data collected from 687 individuals were included in LPA. Identified latent profiles (LPs) were compared on clinical validators. Five LPs were identified: LP1 (n = 178), objective bingeing and multiple purging methods; LP2 (n = 172), objective bingeing without purging; LP3 (n = 130), objective bingeing and vomiting; LP4 (n = 108), low/normal weight and excessive exercise; LP5 (n = 99), low/normal weight and absence of ED symptoms. Validation analyses demonstrated the most extreme psychopathology/medical morbidity in LP1 and the least in LP5. LP1 and LP3 were most likely to report medication treatment for EDs. Identified LPs imperfectly resembled diagnostic and statistical manual of mental disorders-IV-TR EDs. Multiple purging methods and the absence of ED cognitions marked differences in severity across groups, whereas low weight did not. Clinical differences in psychopathology, medical morbidity, and treatment utilization validated groups. Future research should examine longitudinal stability of empirically-derived phenotypes and incremental validity of alternative classification schema to inform DSM-V. [ABSTRACT FROM AUTHOR]

Eating disorder (ED) pathology and its relation to media exposure and globalization were assessed in a sample of young Tanzanian females (N = 214; 19.4 years +/- 3.8 years). Participants completed Kiswahili versions of a DSM-IV ED symptom clinical interview, the Eating Disorder Inventory (EDI), and a media exposure/globalization questionnaire. One third endorsed cognitive ED symptoms; bingeing (10%) and purging (5%) were less common. Four women (1.9%) met modified criteria for anorexia nervosa, one for bulimia nervosa, and 10 (4.7%) reported clinically significant ED pathology consistent with an ED not otherwise specified diagnosis. Media exposure and Western exposure (e.g., travel abroad) were positively associated with ED symptoms. The intended factor structure of the EDI was not supported. Eating pathology is present in this developing nation and is most common in subpopulations with increased exposure to Western culture. Future research should replicate these findings to clarify the role of Western media in the development of ED pathology. [ABSTRACT FROM AUTHOR]

BACKGROUND: Suicide is a common cause of death in anorexia nervosa and suicide attempts occur often in both anorexia nervosa and bulimia nervosa. No studies have examined predictors of suicide attempts in a longitudinal study of eating disorders with frequent follow-up intervals. The objective of this study was to determine predictors of serious suicide attempts in women with eating disorders. METHOD: In a prospective longitudinal study, women diagnosed with either DSM-IV anorexia nervosa (n = 136) or bulimia nervosa (n = 110) were interviewed and assessed for suicide attempts and suicidal intent every 6-12 months over 8.6 years. RESULTS: Fifteen percent of subjects reported at least one prospective suicide attempt over the course of the study. Significantly more anorexic (22.1%) than bulimic subjects (10.9%) made a suicide attempt. Multivariate analyses indicated that the unique predictors of suicide attempts for anorexia nervosa included the severity of both depressive symptoms and drug use over the course of the study. For bulimia nervosa, a history of drug use disorder at intake and the use of laxatives during the study significantly predicted suicide attempts. CONCLUSIONS: Women with anorexia nervosa or bulimia nervosa are at considerable risk to attempt suicide. Clinicians should be aware of this risk, particularly in anorexic patients with substantial co-morbidity. [ABSTRACT FROM AUTHOR]

Objective: To determine whether a past diagnosis of anorexia nervosa (AN) predicts longitudinal course and outcome among women with bulimia nervosa (BN). Method: A subset (n = 176) of participants in the Longitudinal Study of Anorexia and Bulimia Nervosa who met DSM-IV criteria for BN either at study intake (n = 144) or during follow-up (n = 32; 4 had restricting AN at intake, 28 had binge/purge AN at intake) were included in this report. Over a median of 9 years, weekly eating disorder symptom data were collected from participants using the Longitudinal Interview Follow-up Examination, Eating Disorders Version. Results: While there were no between-group differences in likelihood of partial recovery, women with BN who had a history of AN were more likely to have a protracted illness, relapsing into AN during follow-up, compared to those with no AN history who were more likely to move from partial to full recovery. Conclusion: Lifetime AN is an important prognostic indicator among women with BN and these longitudinal data would support the subtyping of BN on the basis of AN history. © 2007 by Wiley Periodicals, Inc. Int J Eat Disord 2007 [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., Competing Interests: Declaration of competing interest Authors KTE and JJE developed CBT-AR and receive royalties from Cambridge University Press for the sale of their books on CBT-AR. They also received consulting fees from Equip Health, and academic speaking fees from other treatment programs, universities, and professional societies. Given this conflict of interest and to ensure the integrity of findings, authors KTE and JJE will not be involved in collection or analysis of data. Authors KTE and JJE will, however, be involved in training and consultation with study clinicians, interpretation of findings and the write-up of publications, and these interests will be disclosed in all material., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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.)

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.)

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.)

Background: The minority of people with an eating disorder receive treatment. Little is known about predictors of receiving treatment., Methods: Using data from the Growing Up Today Study we identified correlates of receiving treatment for an eating disorder among the 1237 U.S. women who answered questions on treatment history in 2013 and reported meeting criteria for subthreshold eating disorder in ≥ 1 year between 1996 and 2013. Logistic regression models using generalized estimating equations were used to estimate the relative odds of receiving treatment., Results: Approximately 11% of the women reported receiving treatment for an eating disorder. Independent of type of eating disorder, those who had received a diagnosis of depression or anxiety were more likely (odds ratio (OR) = 3.05 95% confidence interval (CI) 1.87-4.97) to receive treatment for an eating disorder. Women with obesity were approximately 85% less likely to receive treatment (OR = 0.13, 95% CI 0.04-0.46) regardless of their type of eating disorder or history of depression of anxiety diagnosis., Conclusions: Most women meeting criteria for an eating disorder do not receive treatment. Women with BED or obesity are the least likely to receive treatment., (© 2024. The Author(s).)

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: Proteomics offers potential for detecting and monitoring anorexia nervosa (AN) and its variant, atypical AN (atyp-AN). However, research has been limited by small protein panels, a focus on adult AN, and lack of replication., Methods: In this study, we performed Olink multiplex profiling of 92 inflammation-related proteins in females with AN/atyp-AN ( n  = 64), all of whom were ≤90% of expected body weight, and age-matched healthy control individuals ( n  = 44)., Results: Five proteins differed significantly between the primary AN/atyp-AN group and the healthy control group (lower levels: HGF, IL-18R1, TRANCE; higher levels: CCL23, LIF-R). The expression levels of 3 proteins (lower IL-18R1, TRANCE; higher LIF-R) were uniquely disrupted in participants with AN in our primary model. No unique expression levels emerged for atyp-AN. In the total sample, 12 proteins (ADA, CD5, CD6, CXCL1, FGF-21, HGF, IL-12B, IL18, IL-18R1, SIRT2, TNFSF14, TRANCE) were positively correlated with body mass index and 5 proteins (CCL11, FGF-19, IL8, LIF-R, OPG) were negatively correlated with body mass index in our primary models., Conclusions: Our results replicate the results of a previous study that demonstrated a dysregulated inflammatory status in AN and extend those results to atyp-AN. Of the 17 proteins correlated with body mass index, 11 were replicated from a previous study that used similar methods, highlighting the promise of inflammatory protein expression levels as biomarkers of AN disease monitoring. Our findings underscore the complexity of AN and atyp-AN by highlighting the inability of the identified proteins to differentiate between these 2 subtypes, thereby emphasizing the heterogeneous nature of these disorders., (© 2024 The Authors.)

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: 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.).

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: 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., (© 2023 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).)

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.

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: Studies in estrogen deficiency states such as primary ovarian insufficiency and Turner syndrome suggest that estrogen status may be an important modulator of mood and emotions. In this study we compared depressive and anxiety symptoms between adolescent and young adult female oligo-amenorrheic athletes (AA) and eumenorrheic females (EM), and explored structural, and functional changes in related brain areas during reward processing, a behavioral construct that is altered in depression and anxiety., Methods: We included (i) 24 AA participating in ≥4 hours/week of aerobic exercise or running ≥20 miles/week for ≥6 months in the preceding year, with lack of menstrual cycles for ≥3 months within at least 6 preceding months of oligo-amenorrhea, OR in premenarchal girls, absence of menses at >15 years), and (ii) 27 EM aged 14-25 years. Participants completed the Beck Depression Inventory-II (BDI-II), State and Trait Anxiety Inventory (STAI), and Mood and Anxiety Symptoms Questionnaire (MASQ). Structural MRI and brain activation during a functional MRI (fMRI) task that probes reward and punishment processing was examined in a subset of 10 AA and 23 EM., Results: Median (IQR) age and BMI of AA and EM groups were 20.6 (19.0-22.6) vs. 20.6 (19.2-23.7) years, p=0.6 and v 20.3 (18.8-21.5) vs. 21.9 (19.6-23.5) kg/m2, p=0.005, respectively. While groups did not differ for BDI-II scores, AA had higher anhedonic depression MASQ scores (p=0.04), and STAI (p=0.03) scores vs. EM. In the fMRI subset, AA had higher caudate volumes vs. EM [F(1, 29)=9.930, p=0.004]. Lower activation observed in the right caudate during reward anticipation in AA compared with EM (p=0.036) suggests blunted reward processing in the striatum in estrogen deficient states., Conclusion: Athletes with amenorrhea had higher depressive and anxiety symptomatology compared to eumenorrheic young women. Exploratory analyses demonstrated increased caudate volumes and decreased caudate activation during reward processing in athletes with amenorrhea suggesting that estrogen may play a role in reward processing., Competing Interests: Over the past 3 years, DP has received consulting fees from Albright Stonebridge Group, Boehringer Ingelheim, Compass Pathways, Engrail Therapeutics, Neumora Therapeutcis former BlackThorn Therapeutics, Neurocrine Bioscences, Neuroscience Software, Otsuka Pharmaceuticals, Sunovion Pharmaceuticals, and Takeda Pharmaceuticals; honoraria from the Psychonomic Society for editorial work and Alkermes, and research funding from NIMH, Dana Foundation, Brain and Behavior Research Foundation, Millennium Pharmaceuticals. In addition, he has received stock options from Compass Pathways, Engrail Therapeutics, Neumora Therapeutics former BlackThorn Therapeutics, and Neuroscience Software. Over the past 3 years, MM has received consulting fees from Sanofi and Abbvie, and served on the scientific advisory board for Abbvie and Ipsen. No funding from these entities was used to support the current work, and all views expressed are solely those of the author. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Baskaran, Kumar, Plessow, Nimmala, Ackerman, Eddy, Pizzagalli and Misra.)

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.)

Atypical anorexia nervosa (AN) is not well-defined. Walsh, Hagan, and Lockwood (2022) review the data on atypical AN published in the last decade demonstrating overwhelming clinical similarities between atypical AN and AN. As written, atypical AN includes at least three clinical presentations that may not have the same underlying illness, and in turn, may have different prognoses and treatment needs: (1) higher-weight AN; (2) prodromal AN; and (3) partial remission from AN. While useful for the first two presentations, we suggest that the atypical AN diagnosis is not appropriate for those in partial remission from AN. Extant data document symptom fluctuation is part of illness course in AN rather than crossover to a distinct disorder. Further, lifetime AN carries the greatest risk for relapse to low-weight, premature death, and medical morbidities. Finally, emerging data support unique biobehavioral mechanisms in AN suggesting its combination with atypical AN is premature. Therefore, at this time, we recommend that the atypical AN diagnosis be reserved for those without lifetime AN. We encourage research to test and validate operational definitions of atypical AN and partial remission from AN, and further suggest documentation of lifetime AN across the eating disorders given its prognostic value., (© 2023 Wiley Periodicals LLC.)

Objective: Conduct a systematic review on muscle size and strength in individuals with anorexia nervosa (AN)., Method: In accordance with PRISMA guidelines, we searched Pubmed for articles published between 1995 and 2022 using a combination of search terms related to AN and muscle size, strength, or metabolism. After two authors screened articles and extracted data, 30 articles met inclusion criteria. Data were coded, and a risk bias was conducted for each study., Results: The majority of studies focused on muscle size/lean mass (60%, n = 18) and energy expenditure (33%, n = 9), with few studies (17%, n = 5) investigating muscle function or possible mechanisms underlying muscle size (20%, n = 6). Studies supported that individuals with AN have smaller muscle size and reduced energy expenditure relative to controls. In some studies (33%, n = 10) recovery from AN was not sufficient to restore muscle mass or function. Mechanisms underlying short and long-term musculoskeletal alterations have not been thoroughly explored., Discussion: Muscle mass and strength loss may be an unexplored component of physiological deterioration during and after AN. More research is necessary to understand intramuscular alterations during AN and interventions to facilitate muscle mass and functional gain following weight restoration in AN., Public Significance: Muscle health is important for optimal health and is reduced in individuals with AN. However, we do not understand how muscle is altered at the cellular level throughout the course of AN. Here we review what is currently known regarding muscle health during AN and with weight restoration., (© 2022 Wiley Periodicals LLC.)

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.)

Importance: Individuals with anorexia nervosa maintain extremely low body weights despite elevations in the circulating orexigenic hormone ghrelin. Whether circulating levels of endogenous ghrelin are associated with weight gain in anorexia nervosa is unknown., Objective: To examine the association between baseline ghrelin and future weight change in individuals with anorexia nervosa., Design, Setting, and Participants: This prospective cohort study was conducted between April 1, 2014, and March 31, 2020, in the US. Girls and women aged 10 to 22 years were recruited from the greater Boston area from community and area treatment centers, enrolled, and followed up for 18 months. Statistical analyses were performed between January and August 2022., Exposures: Presence or absence of anorexia nervosa and elevations in endogenous ghrelin., Main Outcomes and Measures: Changes in age- and sex-standardized body mass index percentiles from baseline to 9- and 18-month follow-up were the main outcomes of interest., Results: A total of 68 girls and young women (11 [16%] Asian, 4 [6%] Hispanic or Latina, 51 [75%] White [non-Hispanic or Latina], and 2 [3%] other race or ethnicity), including 35 with anorexia nervosa and 33 healthy controls of similar Tanner stage, were included in this study. Anorexia nervosa and healthy control groups were not statistically different by race and ethnicity, Tanner stage, number completing follow-up visits, and the duration between baseline and follow-up visits. At baseline, individuals with anorexia nervosa were slightly older (median [IQR], 20.1 [18.5-21.0] vs 18.7 [14.7-19.4] years; P = .005), had lower body mass index percentiles (median [IQR], 2.4 [0.3-4.7] vs 52.9 [40.4-68.3]; P < .001), and had elevated circulating ghrelin area under the curve composite index (median [IQR], 1389.4 [1082.5-1646.4] vs 958.5 [743.0-1234.5] pg/mL; P = .003) compared with healthy individuals. In linear mixed-effects regression analyses, baseline ghrelin was associated with prospective weight gain after adjusting for diagnosis, age, race, and duration of follow-up (odds ratio, 2.35; 95% CI, 1.43-3.73; P = .004)., Conclusions and Relevance: In this cohort study, endogenous ghrelin was associated with longitudinal weight gain in individuals with anorexia nervosa. Further studies are warranted to confirm this result and examine its potential clinical utility in treatment development.

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., (© 2023 John Wiley & Sons Ltd.)

Objective: Anorexia nervosa (AN) is commonly associated with depression, anxiety, and deficits in socioemotional functioning. Basal levels of oxytocin, a neurohormone with antidepressant, anxiolytic, and prosocial properties, are low in women with AN. However, the relationship between oxytocin and psychopathology of AN/atypical AN has not been examined in individuals with primarily food restriction (AN/AtypAN-R) or those with restriction plus binge/purge behaviors (AN/AtypAN-BP) alone, which is important to further elucidate the neurobiology of different AN presentations. We investigated whether oxytocin levels are related to eating, affective, and socioemotional psychopathology in women with AN/AtypAN-R and separately AN/AtypAN-BP., Methods: In a cross-sectional study of 53 women with low-weight AN or atypical AN based on DSM-5 (AN/AtypAN-R: n=21, AN/AtypAN-BP: n=32), we obtained fasting serum oxytocin levels and self-report measures of psychopathology, including the Eating Disorder Examination-Questionnaire (EDE-Q), Beck Depression Inventory-IA (BDI), State-Trait Anxiety Inventory (STAI), and Toronto Alexithymia Scale (TAS-20)., Results: In individuals with AN/AtypAN-R, oxytocin levels were negatively associated with eating psychopathology (EDE-Q Global Score: r=-0.49, p=0.024), depressive and anxiety symptoms (BDI Total Score: r=-0.55, p=0.009; STAI Trait Score: r=-0.63, p=0.002), and socioemotional symptoms (TAS-20 Difficulty Identifying Feelings Score: r=-0.49, p=0.023). In contrast, in those with AN/AtypAN-BP oxytocin levels were negatively associated with depressive symptoms only (BDI Total Score: r=-0.52, p=0.049)., Conclusions: These findings support the notion that AN/AtypAN-R and AN/AtypAN-BP might have divergent underlying neurobiology. Understanding these differences is crucial to develop targeted treatments for a population with high levels of chronicity, for which no specific pharmacological treatments are currently available., Clinical Trial Registration: https://clinicaltrials.gov, identifier: NCT01121211., Competing Interests: KM has received study medication from Pfizer and an investigator-initiated research grant from Amgen. She has had equity in Bristol-Myers Squibb, General Electric, Boston Scientific, Amgen, and Becton Dickinson. EL was on the scientific advisory board and has/had a financial interest in OXT Therapeutics, a company that developed oxytocin-based therapeutics for obesity and metabolic disease. She also received an investigator-initiated grant from Tonix Pharmaceuticals. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Plessow, Galbiati, Eddy, Misra, Miller, Klibanski, Aulinas and Lawson.)

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., (© 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.)

Background: 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., Methods: 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/m 2 ). 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., Results: Sixty-one male and female participants aged 18-45 years were randomized (mean age 34 years, mean BMI 37 kg/m 2 ). The study sample is diverse with 38% identifying as non-White and 20% Hispanic., Conclusion: 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., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: E.A.L. served on the scientific advisory board and has a financial interest in OXT Therapeutics, Inc. E.A.L. also received funding for an investigator-initiated study by Tonix Pharmaceuticals. All other authors declare no conflicts of interest., (Copyright © 2022. Published by Elsevier Inc.)

Objective: Anorexia nervosa is complicated by high bone resorption, low bone 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 (aBMD) T-score <-1.0 at ≥1 sites were randomized to 12 months of denosumab (60 mg subcutaneously q6 months)(n = 20) or placebo (n = 10). Primary end point was postero-anterior (PA) lumbar spine aBMD by dual-energy 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 finite 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 increased 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 increased, 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 decreased 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 anorexia nervosa.

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: 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., Method: 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., Results: 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., Conclusion: 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.

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., (© 2022 Wiley Periodicals LLC.)

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.)

Background: While physiologic estrogen replacement results in increases in areal bone mineral density (aBMD) in hypoestrogenic adolescent girls and young adult women with AN, data are lacking regarding its impact on measures of volumetric BMD (vBMD), bone geometry, and structure. Methods: 23 young women with anorexia nervosa (AN) and 27 normal-weight healthy controls (HC) between 14−25 years old were followed for 12 months. AN participants received transdermal 17β-estradiol (continuously) with 10 days of cyclic oral progesterone (100 mg daily) every month for the study duration (AN-E+). DXA was used to measure aBMD and body composition, high resolution peripheral quantitative CT (HRpQCT) to assess vBMD, bone geometry and structure at the distal radius and tibia, and microfinite element analysis to estimate strength. Results: Groups did not differ for age. Median baseline BMI z-scores were −1.13 (−1.58, −0.38) in AN-E+ vs. 0.08 (−0.40, 0.84) in HC (p < 0.0001). For most HRpQCT parameters and strength estimates, young women with AN receiving physiologic estrogen replacement demonstrated similar changes over 12 months as did normoestrogenic HC. Additionally, radial cortical tissue mineral density, cortical vBMD, and failure load increased (p = 0.01; p = 0.02; p = 0.004 respectively) over 12 months in AN-E+ compared to HC. Conclusions: With physiologic estrogen replacement, bone accrual improved in AN to approximate changes observed in normoestrogenic controls followed without any intervention, with additional benefits observed for cortical tissue mineral density, cortical vBMD, and failure load at the radius in AN vs. controls. Thus, this strategy for estrogen replacement effectively mimics the effects of endogenous estrogen on bone structure and estimated strength.