Drug discovery for heart failure targeting myosin-binding protein C.

Cardiac MyBP-C (cMyBP-C) interacts with actin and myosin to fine-tune cardiac muscle contractility. Phosphorylation of cMyBP-C, which reduces the binding of cMyBP-C to actin and myosin, is often decreased in patients with heart failure (HF) and is cardioprotective in model systems of HF. Therefore, cMyBP-C is a potential target for HF drugs that mimic its phosphorylation and/or perturb its interactions with actin or myosin. We labeled actin with fluorescein-5-maleimide (FMAL) and the C0-C2 fragment of cMyBP-C (cC0-C2) with tetramethylrhodamine (TMR). We performed two complementary high-throughput screens (HTS) on an FDA-approved drug library, to discover small molecules that specifically bind to cMyBP-C and affect its interactions with actin or myosin, using fluorescence lifetime (FLT) detection. We first excited FMAL and detected its FLT, to measure changes in fluorescence resonance energy transfer (FRET) from FMAL (donor) to TMR (acceptor), indicating binding. Using the same samples, we then excited TMR directly, using a longer wavelength laser, to detect the effects of compounds on the environmentally sensitive FLT of TMR, to identify compounds that bind directly to cC0-C2. Secondary assays, performed on selected modulators with the most promising effects in the primary HTS assays, characterized the specificity of these compounds for phosphorylated versus unphosphorylated cC0-C2 and for cC0-C2 versus C1-C2 of fast skeletal muscle (fC1-C2). A subset of identified compounds modulated ATPase activity in cardiac and/or skeletal myofibrils. These assays establish the feasibility of the discovery of small-molecule modulators of the cMyBP-C-actin/myosin interaction, with the ultimate goal of developing therapies for HF.

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

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

The potential role of occupational therapy in the treatment of avoidant/restrictive food intake disorder.

Most individuals with avoidant/restrictive food intake disorder (ARFID) never receive treatment, and treatment needs far exceed the current capacity of mental health services. Occupational therapy (OT) focuses on enhancing function in daily activities, including eating and feeding. Given OT's rich history in mental health and pediatric feeding disorder treatment, we spotlight the potential role of OT in ARFID treatment, current knowledge, and opportunities for future research. Through a preliminary exploratory inquiry involving a review of current literature and clinical practice, we investigated OT's current involvement, knowledge, and interprofessional collaborative practice gaps in ARFID treatment. While many occupational therapy practitioners (OTPs) engage in ARFID treatment, interventions lack rigorous evaluation, and there is limited evidence defining OT's distinct role in interprofessional ARFID treatment. OTPs are uniquely positioned to provide interventions for individuals with ARFID across the lifespan, though research is needed to evaluate the efficacy of OT interventions. Future research suggestions include standardizing OT approaches to ARFID treatment and conducting single-case experiments and randomized controlled trials to compare OT approaches with alternative methods. Recommendations to address practice gaps include enhancing ARFID education for OT students and practitioners and fostering a greater understanding of OT's role on the interprofessional team. PUBLIC SIGNIFICANCE: Individuals with ARFID face barriers to eating that impact their health and function. On a multidisciplinary team, OTPs can treat diverse client populations by identifying and addressing barriers to daily participation, such as physical impairments, trauma history, and environmental barriers. More research is needed to evaluate the efficacy of OT practices in ARFID treatment.

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

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

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

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

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

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

Assessing clinician competence in the delivery of cognitive-behavioural therapy for eating disorders: development of the Cognitive-Behavioural Therapy Scale for Eating Disorders (CBTS-ED).

Evidence-based cognitive-behaviour therapy for eating disorders (CBT-ED) differs from other forms of CBT for psychological disorders, making existing generic CBT measures of therapist competence inadequate for evaluating CBT-ED. This study developed and piloted the reliability of a novel measure of therapist competence in this domain-the Cognitive Behaviour Therapy Scale for Eating Disorders (CBTS-ED). Initially, a team of CBT-ED experts developed a 26-item measure, with general (i.e. present in every session) and specific (context- or case-dependent) items. To determine statistical properties of the measure, nine CBT-ED experts and eight non-experts independently observed six role-played mock CBT-ED therapy sessions, rating the therapists' performance using the CBTS-ED. The inter-item consistency (Cronbach's alpha and McDonald's omega) and inter-rater reliability (ICC) were assessed, as appropriate to the clustering of the items. The CBTS-ED demonstrated good internal consistency and moderate/good inter-rater reliability for the general items, at least comparable to existing generic CBT scales in other domains. An updated version is proposed, where five of the 16 "specific" items are reallocated to the general group. These preliminary results suggest that the CBTS-ED can be used effectively across both expert and non-expert raters, though less experienced raters might benefit from additional training in its use.

The Intersection of Disorders of Gut-Brain Interaction With Avoidant/Restrictive Food Intake Disorder.

High rates of overlap exist between disorders of gut-brain interaction (DGBI) and eating disorders, for which common interventions conceptually conflict. There is particularly increasing recognition of eating disorders not centered on shape/weight concerns, specifically avoidant/restrictive food intake disorder (ARFID) in gastroenterology treatment settings. The significant comorbidity between DGBI and ARFID highlights its importance, with 13% to 40% of DGBI patients meeting full criteria for or having clinically significant symptoms of ARFID. Notably, exclusion diets may put some patients at risk for developing ARFID and continued food avoidance may perpetuate preexisting ARFID symptoms. In this review, we introduce the provider and researcher to ARFID and describe the possible risk and maintenance pathways between ARFID and DGBI. As DGBI treatment recommendations may put some patients at risk for developing ARFID, we offer recommendations for practical treatment management including evidence-based diet treatments, treatment risk counseling, and routine diet monitoring. When implemented thoughtfully, DGBI and ARFID treatments can be complementary rather than conflicting.

Assessment and Treatment of Avoidant/Restrictive Food Intake Disorder.

PURPOSE OF REVIEW: To review the literature pertaining to the assessment and treatment of avoidant/restrictive food intake disorder (ARFID) ten years following its introduction to DSM-5. RECENT FINDINGS: Several structured clinical interviews for assessing ARFID have been developed, each with its own strengths and limitations. There is no clear leading self-report measure for tracking treatment progress and outcome in ARFID. Medical assessment is comprised of examining anthropometrics, vitamin deficiencies, and other comorbidities. To date, several studies have reported on cognitive behavioral therapy, family-based treatment, and other approaches to the treatment of ARFID. These treatments appear promising; however, they rely on data from clinical case series and very small randomized controlled trials. Several promising assessments and treatments for ARFID are in the early stages of research. Yet, controversies remain. These include (a) overlap with criteria for pediatric feeding disorder; (b) the optimal method for assessing nutrient deficiencies; (c) disciplines involved in treatment. Future research innovation is necessary to improve the psychometric properties of ARFID assessments and evaluate treatment efficacy with larger samples and randomized designs.

A proposed trumping scheme for other specified feeding or eating disorder: Comment on Walsh et al., 2023.

The recent systematic review by Walsh, Hagan, & Lockwood (Int J Eat Disord, 2022) highlights the importance of further distinguishing atypical anorexia nervosa (atypical AN) from other feeding and eating disorders. The lack of a trumping scheme within other specified feeding or eating disorder (OSFED) hinders intervention selection in the clinical context and reduces reliability of diagnostic classification in research samples. Thus, we propose a trumping scheme within OSFED that mirrors the existing diagnostic algorithm in the main DSM-5-TR feeding and eating disorders section. According to this scheme, a diagnosis of atypical AN would override all other OSFED subcategories. Subthreshold bulimia nervosa (BN) would trump subthreshold binge-eating disorder (BED) and purging disorder; purging disorder would trump subthreshold BED and night eating syndrome; night eating syndrome would trump subthreshold BED; and subthreshold BED would trump subthreshold avoidant/restrictive food intake disorder (ARFID)-a novel presentation that we propose adding under the OSFED umbrella to parallel the existing subthreshold classifications for the main feeding and eating disorders. We hope this proposed OSFED trumping scheme will improve intervention selection and diagnostic reliability in clinical and research contexts, and serve as a catalyst for future research on these newly recognized-but common and impairing-feeding and eating disorder presentations.

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

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

Prevalence and Characteristics of Avoidant/Restrictive Food Intake Disorder in Pediatric Neurogastroenterology Patients.

ABSTRACT: Recent reports document avoidant/restrictive food intake disorder (ARFID) symptoms among 13-40% of adults presenting to neurogastroenterology clinics, but ARFID in pediatrics is understudied. We conducted a retrospective review of charts from 129 consecutive referrals (ages 6-18 years; 57% female) for pediatric neurogastroenterology examination, from January 2016 through December 2018. Eleven cases (8%) met the full criteria for ARFID by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition and 19 cases (15%) had clinically significant avoidant/ restrictive eating behaviors with insufficient information for a definitive ARFID diagnosis. Of patients with ARFID symptoms (n = 30), 20 (67%) cited fear of gastrointestinal symptoms as motivation for their avoidant/ restrictive eating. Compared to patients without ARFID symptoms, patients with ARFID symptoms were older (P  < .001), more likely to be female (51% vs 79%, P  = 0.014), and more frequently presented with eating/weight-related complaints (15% vs 33%, P  = 0.026). This pilot retrospective study showed ARFID symptoms present in 23% of pediatric neurogastroenterology patients; further research is needed to understand risk and maintenance factors of ARFID in the neurogastroenterology setting.

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

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

Anhedonia in eating disorders: A meta-analysis and systematic review.

OBJECTIVE: Anhedonia, or loss of pleasure, is related to deficits in reward processing across a variety of psychiatric disorders. In light of research suggesting abnormal reward processing in eating disorders (EDs), the study of anhedonia in EDs may yield important insights into the role of reward in eating pathology. This meta-analysis and review aimed to provide both a quantitative and qualitative synthesis of the existing literature on this topic. METHOD: We conducted this research (or these meta-analyses) according to PRISMA guidelines. We searched four databases for both peer-reviewed and unpublished literature, and included studies only if a self-report or clinical interview measure of anhedonia was administered to a sample with an ED diagnosis. RESULTS: We included 21 studies in the systematic review, and 10 studies in two meta-analyses that compared anhedonia between ED and control samples (n = 9 studies) and within different ED diagnoses (n = 5 studies). Meta-analyses revealed that anhedonia was significantly higher in ED groups compared to healthy controls, but there was no significant difference in anhedonia between ED diagnostic groups. A qualitative review of the literature also suggested that anhedonia may be correlated with increased ED symptom severity. DISCUSSION: Findings indicated that anhedonia is elevated in EDs and may be a relevant treatment target. Future research should examine how self-reported anhedonia may correlate with components of reward processing in EDs in order to improve theoretical models as well as targeted interventions.

OBJETIVO: La anhedonia, o pérdida de placer, está relacionada con déficits en el procesamiento de recompensas en una variedad de trastornos psiquiátricos. A la luz de la investigación que sugiere una anormalidad en el proceso de la recompensa en los trastornos de la conducta alimentaria (TCA), el estudio de la anhedonia en los TCA puede producir información importante sobre el papel de la recompensa en la patología alimentaria. Este metanálisis y revisión tuvo como objetivo proporcionar una síntesis cuantitativa y cualitativa de la literatura existente sobre este tema. MÉTODO: Se realizó esta investigación (o estos metanálisis) de acuerdo con las guías PRISMA. Se realizaron búsquedas en cuatro bases de datos de literatura revisada por pares y no publicada, y se incluyeron estudios solo si se administró una medida de anhedonia en el autoreporte o en una entrevista clínica a una muestra con un diagnóstico de TCA. RESULTADOS: Se incluyeron 21 estudios en la revisión sistemática y 10 estudios en dos metanálisis que compararon la anhedonia entre TCA y las muestras de control (n = 9 estudios) y dentro de diferentes diagnósticos de TCA (n = 5 estudios). Los metanálisis revelaron que la anhedonia fue significativamente mayor en los grupos de TCA en comparación con los controles sanos, pero no hubo diferencias significativas en la anhedonia entre los grupos de diagnóstico de TCA. Una revisión cualitativa de la literatura también sugirió que la anhedonia puede estar correlacionada con una mayor gravedad de los síntomas de TCA. DISCUSIÓN: Los hallazgos indicaron que la anhedonia está elevada en los TCA y puede ser un objetivo de tratamiento relevante. La investigación futura debe examinar cómo la anhedonia autoreportada puede correlacionarse con los componentes del procesamiento de recompensas en los TCA para mejorar los modelos teóricos, así como las intervenciones dirigidas.

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

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

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

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

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

OBJECTIVE: Avoidant/restrictive food intake disorder (ARFID) occurs across the weight spectrum, however research addressing the coexistesnce of ARFID with overweight/obesity (OV/OB) is lacking. We aimed to establish co-occurrence of OV/OB and ARFID and to characterize divergent neurobiological features of ARFID by weight. METHOD: Youth with full/subthreshold ARFID (12 with healthy weight [HW], 11 with OV/OB) underwent fasting brain fMRI scan while viewing food/non-food images (M age = 16.92 years, 65% female, 87% white). We compared groups on BOLD response to high-calorie foods (HCF) (vs. objects) in food cue processing regions of interest. Following fMRI scanning, we evaluated subjective hunger pre- vs. post-meal. We used a mediation model to explore the association between BMI, brain activation, and hunger. RESULTS: Participants with ARFID and OV/OB demonstrated significant hyperactivation in response to HCF (vs. objects) in the orbitofrontal cortex (OFC) and anterior insula compared with HW participants with ARFID. Mediation analysis yielded a significant indirect effect of group (HW vs. OV/OB) on hunger via OFC activation (effect = 18.39, SE = 11.27, 95% CI [-45.09, -3.00]), suggesting that OFC activation mediates differences in hunger between ARFID participants with HW and OV/OB. CONCLUSIONS: Compared to youth with ARFID and HW, those with OV/OB demonstrate hyperactivation of brain areas critical for the reward value of food cues. Postprandial changes in subjective hunger depend on BMI and are mediated by OFC activation to food cues. Whether these neurobiological differences contribute to selective hyperphagia in ARFID presenting with OV/OB and represent potential treatment targets is an important area for future investigation.

Eighteen-month Course and Outcome of Adolescent Restrictive Eating Disorders: Persistence, Crossover, and Recovery.

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.

Introduction to a special issue on eating disorders in Asia.

OBJECTIVE: It is our pleasure to introduce a special issue of the International Journal of Eating Disorders on eating disorders (EDs) in Asia. METHOD: We received such a robust response to the special edition that we were able to fill two issues. Contributions focused on seven main themes: (1) prevalence, (2) time trends, (3) healthcare systems, (4) treatment, (5) risk factors, (6) assessment, and (7) orthorexia. RESULTS: New prevalence and time trend data from China, Iran, Singapore, Japan, and Taiwan suggest that EDs are increasingly common in Asia but are not always detected in healthcare settings. Only a minority of individuals with EDs in Singapore receive treatment, and psychosocial treatment and prevention interventions that are evidence-based in the West may require cultural adaptation before they can be fully implemented in Japan, Singapore, China, and South Korea. Psychological risk factors for EDs are more similar than different in Iran, India, Japan, and China, but biological risk factors are understudied across the continent. Psychometrically sound assessment tools are available in many Asian languages. DISCUSSION: We hope this special issue provides a catalyst and blueprint for global collaboration to relieve the burden of suffering of EDs in Asia and beyond.

Validation of the nine item ARFID screen (NIAS) subscales for distinguishing ARFID presentations and screening for ARFID.

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