Development of a transdiagnostic digital interactive application for eating disorders: psychometric properties, satisfaction, and perceptions on implementation in clinical practice.

BACKGROUND: Given limited availability of informed treatments for people affected by eating disorders (EDs), there has been increasing interest in developing self-administered, technology-based ED interventions. However, many available interventions are limited to a specific ED diagnosis or assume that participants are ready to change. We developed a digital self-help application (called ASTrA) that was explicitly designed to be transdiagnostic and to help increase motivation for change. The aim of the present study was to describe the development and examine the psychometric properties, user satisfaction and rated potentials for practical use of our application. METHODS: The content of our application was based on concepts derived from self-determination theory, the transtheoretical model of change, and cognitive theory. The application was developed by a multidisciplinary team of clinicians, researchers, staff members and individuals with lived ED experience, each being involved in all steps of the application's development. We tested validity, reliability, satisfaction and perceived feasibility for clinical implementation in an independent sample of 15 patients with an ED and 13 clinicians specialized in ED treatment. Psychometric properties were evaluated using descriptive statistics, correlations, content validity indices and intraclass coefficients. Differences in satisfaction ratings and perceived potential for clinical implementation of the application between clinicians and patients were examined using Mann-Whitney U tests. RESULTS: The digital application showed excellent validity (mean i-CVI: .93, range: .86-.96) and internal reliability (all Cronbach alpha's > .88). Patients and clinicians both considered the application acceptable, appropriate, and feasible for use in clinical practice. CONCLUSIONS: Findings suggest that our transdiagnostic interactive application has excellent psychometric properties. Furthermore, patients and clinicians alike were positive about the possible use of the application in clinical practice. The next step will be to investigate the application's effectiveness as an intervention to promote autonomous motivation and to facilitate remission in people on the waitlist for specialized ED treatment.

DNA methylation in people with anorexia nervosa: Epigenome-wide patterns in actively ill, long-term remitted, and healthy-eater women.

OBJECTIVES: Recent studies have reported altered methylation levels at disorder-relevant DNA sites in people who are ill with Anorexia Nervosa (AN) compared to findings in people with no eating disorder (ED) or in whom AN has remitted. The preceding implies state-related influences upon gene expression in people with AN. This study further examined this notion. METHODS: We measured genome-wide DNA methylation in 145 women with active AN, 49 showing stable one-year remission of AN, and 64 with no ED. RESULTS: Comparisons revealed 205 differentially methylated sites between active and no ED groups, and 162 differentially methylated sites between active and remitted groups (Q < 0.01). Probes tended to map onto genes relevant to psychiatric, metabolic and immune functions. Notably, several of the genes identified here as being differentially methylated in people with AN (e.g. SYNJ2, PRKAG2, STAT3, CSGALNACT1, NEGR1, NR1H3) have figured in previous studies on AN. Effects also associated illness chronicity and lower BMI with more pronounced DNA methylation alterations, and remission of AN with normalisation of DNA methylation. CONCLUSIONS: Findings corroborate earlier results suggesting reversible DNA methylation alterations in AN, and point to particular genes at which epigenetic mechanisms may act to shape AN phenomenology.

Barriers and Facilitators to the Implementation of an Eating Disorders Knowledge Exchange Program for Non-specialist Professionals.

Despite availability of evidence-based treatments for eating disorders (EDs), individuals with EDs often do not receive informed treatment. Training of non-specialized clinicians by experienced professionals through knowledge exchange (KE) programs is an effective way to enhance accessibility to evidence-based treatments for EDs. The authors conducted a qualitative analysis of factors that facilitated or impeded the uptake of an ED-focused KE program. Semi-structured interviews were conducted with mental health professionals (n = 43) and managers (n = 11) at 13 community mental-health sites at which the KE program was offered. Data were analyzed using a qualitative content analysis. Key facilitators identified were management support for the program and building competence through ongoing supervision of clinicians. Main barriers were limited access to ED patients to treat and having insufficient time to apply ED interventions in front-line settings. The results provide insights into the practical imperatives involved in implementing a KE initiative for ED treatment.

Barriers and facilitators to providing autonomy supportive counselling to individuals seeking treatment for an eating disorder.

PURPOSE: Self-determination theory suggests that autonomous motivation for change (i.e., motivation that is internal and self-endorsed) can be enhanced in therapeutic contexts by clinicians acting in an autonomy supportive manner. While previous research has established a link between autonomy support (AS) and autonomous motivation in enhancing outcomes in eating disorder (ED) treatment, few studies have examined factors that support or hinder therapists' ability to be autonomy supportive in the context of an ED therapeutic encounter. The goal of the present study was to conduct a qualitative analysis of personal and contextual factors that facilitated or hindered therapists' ability to provide autonomy supportive interventions. METHODS: Semi-structured interviews were conducted with 10 therapists conducting outpatient psychotherapy at a specialized eating disorders treatment program. Data were analyzed using thematic analysis. RESULTS: The most frequently noted facilitators were organizational support of AS interventions and patients' engagement and motivation for treatment. The most frequently noted barriers were patients' personality variables such as patients that exhibit passive and help-rejecting behaviours, as well as therapists feeling overwhelmed due to a high workload. CONCLUSION: Our results provide insight into the factors that facilitate and impede the utilization of an autonomy supportive approach in specialized ED treatment and can be used to inform future quantitative research on such factors. LEVEL OF EVIDENCE: Level V: Opinions of respected authorities, based on descriptive studies, narrative reviews, clinical experience, or reports of expert committees.

In-person versus virtual therapy in outpatient eating-disorder treatment: A COVID-19 inspired study.

OBJECTIVE: Findings show virtual therapy (conducted using internet-based videoconferencing techniques) to be a viable alternative to in-person therapy for a variety of mental-health problems. COVID-19 social-distancing imperatives required us to substitute virtual interventions for in-person sessions routinely offered in our outpatient eating disorder (ED) program-and afforded us an opportunity to compare the two treatment formats for clinical efficacy. METHODS: Using self-report assessments, we compared outcomes in a historical sample of 49 adults with heterogeneous EDs (treated in-person over 10-14 weeks in individual and group therapies) to those of 76 patients receiving comparable virtual treatments, at distance, during the COVID-19 outbreak. Linear mixed models were used to study symptom changes over time and to test for differential effects of treatment modality. RESULTS: Participants in both groups showed similar improvements on eating symptoms, levels of weight gain (in individuals in whom gain was indicated), and satisfaction with services. DISCUSSION: Our results suggest that short-term clinical outcomes with virtual and in-person ED therapies are comparable, and point to potentials of virtual therapy for situations in which geographical distance or other barriers impede physical access to trained therapists or specialized treatments.

Predictors of non-completion of a day treatment program for adults with eating disorders.

Although treatment dropout is common among patients with eating disorders, very few studies have examined predictors of non-completion in day treatment. We investigated various potential predictors of dropout from adult day treatment. Participants were 295 adult patients with a diagnosis of Anorexia Nervosa (restricting or binge-eating/purging subtype), Bulimia Nervosa (BN), Other Specified Feeding or Eating Disorder, or Avoidant Restrictive Food Intake Disorder. Predictors included eating-disorder characteristics, motivation at the commencement of treatment, Body Mass Index (BMI), time spent in treatment and personality dimensions. Logistic regression analyses showed that for patients with a BMI of less than 20 at the start of treatment, low BMI was a significant predictor of staff-initiated termination due to not meeting weight gain goals. Furthermore, completing less than 6 weeks of treatment was associated with staff-initiated termination. For the whole sample, those with higher changes in weight over the course of treatment were less likely to terminate prematurely. None of the other predictor variables yielded significant results. Results of the current study highlight characteristics of patients who are more likely not to complete day treatment and can help identify patients who may be at risk for not succeeding in multi-diagnostic day treatment programs.

Plasma levels of one-carbon metabolism nutrients in women with anorexia nervosa.

OBJECTIVE: People who are ill with anorexia nervosa (AN) show altered availability of key plasma nutrients. However, little is known about the patterning of alterations that occurs across diverse nutrients during active phases of illness or about the persistence of any such alterations following remission of illness. METHOD: We compared plasma levels of one-carbon metabolism nutrients across women with active AN (AN-Active: n = 53), in remission from AN (AN-Remitted: n = 40), or who had no eating-disorder history (NED: n = 36). We also tested associations between body mass index (BMI) changes and changes in pre- to posttreatment nutrient levels, and explored the association between nutrient levels, on the one hand, and BMI and eating symptoms, on the other. Choline, betaine, and methionine were analyzed using mass spectrometry. Folate and B12 were analyzed using the AccuBind® ELISA kit. Eating-disorder symptoms were assessed by interview and self-report. RESULTS: Compared to NED individuals, AN-Active individuals exhibited significantly elevated B12 and (less-reliably) betaine. In AN-Active individuals, lower BMI was associated with higher B12. DISCUSSION: The observed alterations run contrary to the intuition that plasma nutrient levels should be directly responsive to nutritional status and suggest, instead, the existence of compensatory adaptations to malnutrition in individuals with active AN. Further study is required to clarify mechanisms that underlie such effects.

Methylation of the OXTR gene in women with anorexia nervosa: Relationship to social behavior.

DNA methylation allows for the environmental regulation of gene expression and is believed to link environmental stressors to psychiatric disorder phenotypes, such as anorexia nervosa (AN). The oxytocin receptor (OXTR) gene is epigenetically regulated, and studies have shown associations between OXTR and social behaviours in various samples, including women with AN. The present study examined differential levels of methylation at various CG sites of the OXTR gene in 69 women with active AN (AN-Active), 21 in whom AN was in remission (AN-Rem) and 35 with no eating disorder (NED). Within each group, we explored the correlation between methylation and measures of social behaviour such as insecure attachment and social avoidance. Hypermethylation of a number of CG sites was seen in AN-Active participants as compared with AN-Rem and NED participants. In the AN-Rem sample, methylation at CG27501759 was significantly positively correlated with insecure attachment (r = .614, p = .003, permutation Q = 0.008) and social avoidance (r = .588, p = .005, permutation Q = 0.0184). Our results highlight differential methylation of the OXTR gene among women with AN, those in remission from AN, and those who never had AN and provide some evidence of associations between OXTR methylation and social behaviour in women remitted from AN.

A naturalistic comparison of two inpatient treatment protocols for adults with anorexia nervosa: Does reducing duration of treatment and external controls compromise outcome?

OBJECTIVE: Although hospitalization is sometimes necessary when treating individuals with anorexia nervosa, the available literature provides limited guidance to inform decisions surrounding optimal components or duration of inpatient treatments. We report observational data comparing outcomes of two inpatient treatments. The first was longer and more strictly structured around a Contingency Management Protocol (CMP) emphasizing external incentives for achieving weight-restoration goals; the second was a shorter Autonomy Support Protocol (ASP) that progressively increased patient autonomy around meal management without external incentives. METHOD: We compared data from 41 patients who participated in the ASP to a historical sample of 41 patients treated using the CMP. At admission, discharge, and post-treatment follow-up, participants completed the Eating Disorder Examination Questionnaire and the Behavior and Symptom Identification Scale-32, and we measured height and weight to compute body mass index. RESULTS: Multilevel modeling analyses that controlled for time in treatment and time in follow-up indicated the two protocols yielded equivalent in-treatment gains and post-treatment loss of gains. DISCUSSION: Our results indicate that shorter inpatient stays emphasizing autonomous control over eating behavior may yield outcomes that are equivalent to those of lengthier, more stringent, and more costly approaches implicating external incentives and controls.

A longitudinal, epigenome-wide study of DNA methylation in anorexia nervosa: results in actively ill, partially weight-restored, long-term remitted and non-eating-disordered women

Background: This study explored state-related tendencies in DNA methylation in people with anorexia nervosa. Methods: We measured genome-wide DNA methylation in 75 women with active anorexia nervosa (active), 31 women showing stable remission of anorexia nervosa (remitted) and 41 women with no eating disorder (NED). We also obtained post-intervention methylation data from 52 of the women from the active group. Results: Comparisons between members of the active and NED groups showed 58 differentially methylated sites (Q < 0.01) that corresponded to genes relevant to metabolic and nutritional status (lipid and glucose metabolism), psychiatric status (serotonin receptor activity) and immune function. Methylation levels in members of the remitted group differed from those in the active group on 265 probes that also involved sites associated with genes for serotonin and insulin activity, glucose metabolism and immunity. Intriguingly, the direction of methylation effects in remitted participants tended to be opposite to those seen in active participants. The chronicity of Illness correlated (usually inversely, at Q < 0.01) with methylation levels at 64 sites that mapped onto genes regulating glutamate and serotonin activity, insulin function and epigenetic age. In contrast, body mass index increases coincided (at Q < 0.05) with generally increased methylation-level changes at 73 probes associated with lipid and glucose metabolism, immune and inflammatory processes, and olfaction. Limitations: Sample sizes were modest for this type of inquiry, and findings may have been subject to uncontrolled effects of medication and substance use. Conclusion: Findings point to the possibility of reversible epigenetic alterations in anorexia nervosa, and suggest that an adequate pathophysiological model would likely need to include psychiatric, metabolic and immune components.

Correction to: A Tertiary-Care/Primary-Care Partnership Aimed at Improving Care for People with Eating Disorders.

The original version of this article unfortunately contained a mistake in EAT-26 values under "Patients Receiving Treatment for an ED in their Sector" section.

A Tertiary-Care/Primary-Care Partnership Aimed at Improving Care for People with Eating Disorders.

We describe the implementation and impact of a province-wide program of knowledge exchange (KE), aimed at developing capacity for the treatment of people with eating disorders (EDs). The program is designed to equip clinicians working in nonspecialized health-care installations with skills to evaluate and treat people with EDs. Trainings were conducted at 21 institutions. The majority of clinicians reported satisfaction with the KE program and indicated that the trainings enhanced their confidence and ability to treat patients with EDs. A subset of clinicians received case supervision with a specialist ED therapist and followed patients with EDs (n = 119). Treated patients showed significant improvements on eating and depressive symptoms, and reported satisfaction with the treatments they received.

Autonomy support and autonomous motivation in the outpatient treatment of adults with an eating disorder.

OBJECTIVE: Across diverse clinical problems, therapists' autonomy support has been found to increase patients' autonomous motivation for change. Being self-motivated has, in turn, been linked to superior treatment response. In people undergoing outpatient eating disorder (ED) treatment, we examined associations among ratings of autonomy support received from therapists and other carers, self-reported engagement in therapy, and clinical outcomes. METHOD: Ninety-seven women with anorexia nervosa, bulimia nervosa, or a related ED provided measures of motivational status and clinical symptoms at the beginning and end of time-limited (12-16 weeks) segments of specialized treatment. At mid-treatment, patients also rated the extent to which they perceived their individual therapists, group therapists, group-therapy peers, family members, friends, and romantic partners as being autonomy supportive. RESULTS: Overall, multiple regression analyses indicated autonomy support to moderate (rather than mediate) the link between initial autonomous motivation and later change in autonomous motivation-with results indicating that, independently of ED diagnosis or treatment intensity, greater perceived autonomy support (from therapists and nontherapists alike) coincided with larger increases in autonomous motivation over the course of therapy. In turn, higher autonomous motivation at end-of-therapy coincided with larger reductions in eating symptoms. DISCUSSION: Findings suggest that the experience of autonomy support (from therapists and nontherapists) is associated with increasing motivation in people undergoing ED treatment, and that becoming self-motivated is linked to better outcomes. Such results indicate that support from therapists, relatives, and peers can favorably influence personal engagement in individuals undergoing ED treatment.

Eating Disorders and Epigenetics.

Eating disorders (EDs) are characterized by intense preoccupation with shape and weight and maladaptive eating practices. The complex of symptoms that characterize EDs often arise through the activation of latent genetic potentials by environmental exposures, and epigenetic mechanisms are believed to link environmental exposures to gene expression. This chapter provides an overview of genetic factors acting in the etiology of EDs. It then provides a background to the hypothesis that epigenetic mechanisms link stresses such as obstetric complications and childhood abuse as well as effects of malnutrition to eating disorders (EDs). The chapter then summarizes the emerging body of literature on epigenetics and EDs-mainly studies on DNA methylation in samples of anorexia and bulimia. The available evidence base suggests that an epigenetically informed perspective contributes in valuable ways to the understanding of why people develop EDs.

Epistatic interactions involving DRD2, DRD4, and COMT polymorphisms and risk of substance abuse in women with binge-purge eating disturbances.

Substance abuse is common in individuals with bulimia-spectrum (binge-purge) eating disturbances, a co-occurrence that has been attributed to shared neurobiological substrates--notably alterations in dopaminergic activity. We examined the implications of variations of selected, dopamine-relevant polymorphisms (DRD2 Taq1A, DRD4 7R, and COMT) for risk of substance abuse in women with binge-purge eating syndromes. We genotyped 183 women (66.1% showing full-threshold BN and 33.9% showing sub-syndromic variants), and assessed lifetime presence of alcohol, cannabis, cocaine, and stimulant abuse or dependence using structured interviews. Tests for main and interaction effects of various allele combinations revealed that individuals who carried high function COMT and low-function DRD4 7R alleles (a combination expected to be associated with higher risk) did indeed show more lifetime substance abuse and, specifically, more cannabis abuse. Our findings suggest that a gene combination that, in theory, codes for low levels of dopaminergic neurotransmission coincides with sensitivity to substance abuse in a sample displaying binge-purge eating-disorder variants.

An examination of the role of autonomous versus controlled motivation in predicting inpatient treatment outcome for anorexia nervosa.

OBJECTIVE: We explored the effect of autonomous and controlled motivation on outcomes for patients undergoing inpatient treatment for Anorexia Nervosa (AN). METHOD: Data on 80 patients with AN were available for the start of treatment, and for 49 at end of treatment. Patients completed measures of autonomous and controlled motivation, eating disorder symptoms and attitudes, and comorbid psychopathology at the start and end of treatment. RESULTS: Patients showed significant improvements on eating symptoms and comorbid psychopathology over the course of treatment. Autonomous motivation was a significant predictor of change in severity of eating symptoms and attitudes such that patients with higher pre-treatment levels of autonomous motivation showed larger post-treatment reductions on these indices. No such effects were associated with controlled motivation. DISCUSSION: This study highlights a relationship between autonomous motivation and outcome in an inpatient setting. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:626-629).

Eating disorders, gene-environment interactions and the epigenome: Roles of stress exposures and nutritional status.

Epigenetic mechanisms are believed to link environmental exposures to gene expression, and in so doing, to provide a physical basis for the activation, by life experiences, of mental-health problems. This paper provides a background to the hypothesis that epigenetic mechanisms link life stresses (perinatal, childhood and adult) and effects of malnutrition to the eating disorders (EDs). The paper reviews literature bearing upon the putative link between epigenetic factors and ED development, and examines ways in which epigenetic alterations could account for risk of eating disturbances and commonly associated behavioral and emotional problems. Ultimately, we propose that epigenetic processes provide an intriguing (although hypothetical) biological "platform" upon which ED-relevant effects of perinatal insults, life stresses, and consequences of malnutrition may be registered, and argue that an epigenetically informed understanding may explain why EDs are triggered and maintained by excessive caloric restraint, why they coincide so frequently with mood- and impulse-regulation problems, and why they tend to become increasingly entrenched over time. Finally, we comment on the clinical relevance and implications of an epigenetically informed model of ED etiology.

A prospective study of effects of prenatal maternal stress on later eating-disorder manifestations in affected offspring: preliminary indications based on the Project Ice Storm cohort.

BACKGROUND: Research associates maternal stress exposures (especially when occurring late in gestation) with heightened risk of subsequent emotional and behavioral problems in affected offspring. However, as yet, no study has examined the association between prenatal maternal stress (PNMS) and affected children's risk of anorexia- or bulimia-type eating disturbances. OBJECTIVE: To study the influences of PNMS on later disordered eating in exposed offspring. METHOD: We used the Eating Attitudes Test (EAT)-26 to measure eating attitudes and behaviors in 54 thirteen-year olds whose mothers had been exposed, while pregnant with these children, to the 1998 Quebec Ice Storm-a natural disaster regarded as a model of exposure to severe environmental stress. Mothers' stress was measured shortly after exposure to the storm using established indices of objective and subjective stress. RESULTS: Hierarchical multiple linear regression analyses indicated that once variance owing to children's body mass index and sex was accounted for, stress exposures during the third trimester of pregnancy predicted elevated EAT-26 scores in affected children-perhaps even more so when levels of objective stress were high. DISCUSSION: Third trimester exposure to PNMS, especially when objectively severe, seems to be associated with increased eating-disorder-linked manifestations in affected early adolescents.

n-back task performance and corresponding brain-activation patterns in women with restrictive and bulimic eating-disorder variants: preliminary findings.

Eating disorder (ED) variants characterized by "binge-eating/purging" symptoms differ from "restricting-only" variants along diverse clinical dimensions, but few studies have compared people with these different eating-disorder phenotypes on measures of neurocognitive function and brain activation. We tested the performances of 19 women with "restricting-only" eating syndromes and 27 with "binge-eating/purging" variants on a modified n-back task, and used functional magnetic resonance imaging (fMRI) to examine task-induced brain activations in frontal regions of interest. When compared with "binge-eating/purging" participants, "restricting-only" participants showed superior performance. Furthermore, in an intermediate-demand condition, "binge-eating/purging" participants showed significantly less event-related activation than did "restricting-only" participants in a right posterior prefrontal region spanning Brodmann areas 6-8-a region that has been linked to planning of motor responses, working memory for sequential information, and management of uncertainty. Our findings suggest that working memory is poorer in eating-disordered individuals with binge-eating/purging behaviors than in those who solely restrict food intake, and that observed performance differences coincide with interpretable group-based activation differences in a frontal region thought to subserve planning and decision making.

Methylation of BDNF in women with bulimic eating syndromes: associations with childhood abuse and borderline personality disorder.

DNA methylation allows for the environmental regulation of gene expression and is believed to link environmental stressors to such mental-illness phenotypes as eating disorders. Numerous studies have shown an association between bulimia nervosa (BN) and variations in brain-derived neurotrophic factor (BDNF). BDNF has also been linked to borderline personality disorder (BPD) and to such traits as reward dependence. We examined the extent to which BDNF methylation corresponded to bulimic or normal-eater status, and also to the presence of comorbid borderline personality disorder (BPD) and childhood abuse. Our sample consisted of 64 women with BN and 32 normal-eater (NE) control women. Participants were assessed for eating-disorder symptoms, comorbid psychopathology, and childhood trauma, and then they were required to provide blood samples for methylation analyses. We observed a significant site×group (BN vs. NE) interaction indicating that women with BN showed increases in methylation at specific regions of the BDNF promoter. Furthermore, examining effects of childhood abuse and BPD, we observed significant site×group interactions such that groups composed of individuals with childhood abuse or BPD had particularly high levels of methylation at selected CpG sites. Our findings suggest that BN, especially when co-occurring with childhood abuse or BPD, is associated with a propensity towards elevated methylation at specific BDNF promoter region sites. These findings imply that hypermethylation of the BDNF gene may be related to eating disorder status, developmental stress exposure, and comorbid psychopathology.