Epigenetic alterations in patients with anorexia nervosa-a systematic review.

Anorexia nervosa (AN) is a complex metabolic and psychological disorder that is influenced by both heritable genetic components and environmental factors. Exposure to various environmental influences can lead to epigenetically induced changes in gene expression. Epigenetic research in AN is still in its infancy, and studies to date are limited in determining clear, valid links to disease onset and progression are limited. Therefore, the aim of this systematic review was to compile and critically evaluate the available results of epigenetic studies specifically in AN and to provide recommendations for future studies. In accordance with the PRISMA guidelines, a systematic literature search was performed in three different databases (PubMed, Embase, and Web of Science) through May 2023. Twenty-three original papers or conference abstracts on epigenetic studies in AN were collected. Epigenome-wide association studies (EWASs), which analyze DNA methylation across the genome in patients with AN and identify potential disease-relevant changes in promoter/regulatory regions of genes, are the most promising for future research. To date, five EWASs on AN have been published, suggesting a potential reversibility of malnutrition-induced epigenetic changes once patients recover. Hence, determining differential DNA methylation levels could serve as a biomarker for disease status or early diagnosis and might be involved in disease progression or chronification. For future research, EWASs with a larger sample size, longitudinal study design and uniform methods should be performed to contribute to the understanding of the pathophysiology of AN, the development of individual interventions and a better prognosis for affected patients.

"You mean it's more than just an eating disorder?": Commentary on Wade et al. (2023).

Drawing from literature on measurement-based care and prognostic indices in eating disorder (ED) treatment, Wade et al. offer an algorithm for treating co-occurring mental-health conditions (i.e., psychiatric comorbidity) in people with EDs, and for studying effects of comorbidity-oriented treatments. Advocating session-by-session measurement to inform adaptive treatment, their proposal outlines a process for adjusting conventional ED treatment to situations in which comorbidity impedes treatment progress. The plan is methodical and responsive to evidence suggesting that peoples' early in-treatment change has more power, prognostically, than do indices of comorbidity. In the absence of data to inform practices in some areas, the authors intentionally leave key questions unanswered until future results are in. But this means that they reserve comment on how to determine that comorbidity is interfering with treatment response, or to select the best-fitting of available comorbidity-oriented options. Likewise, the proposal draws most of its inspiration from literature on individual (mainly cognitive-behavioral) psychotherapy and, as a result, does not fully represent biopsychosocial perspectives, or elaborate upon the place in comorbidity management of biological treatments, family, and carer involvement, or more complex integrated approaches. Considerations on how to apply the latter methods would broaden the plan's scope.

International consensus on patient-centred outcomes in eating disorders.

The effectiveness of mental health care can be improved through coordinated and wide-scale outcome measurement. The International Consortium for Health Outcomes Measurement has produced collaborative sets of outcome measures for various mental health conditions, but no universal guideline exists for eating disorders. This Position Paper presents a set of outcomes and measures for eating disorders as determined by 24 international experts from professional and lived experience backgrounds. An adapted Delphi technique was used, and results were assessed through an open review survey. Final recommendations suggest outcomes should be tracked across four domains: eating disorder behaviours and cognitions, physical health, co-occurring mental health conditions, and quality of life and social functioning. Outcomes are collected using three to five patient-reported measures. For children aged between 6 years and 12 years, the measures include the Children's Eating Attitude Test (or, for those with avoidant restrictive food intake disorder, the Eating Disorder in Youth Questionnaire), the KIDSCREEN-10, and the Revised Children's Anxiety and Depression Screener-25. For adolescents aged between 13 years and 17 years, the measures include the Eating Disorder Examination Questionnaire (EDE-Q; or, for avoidant restrictive food intake disorder, the Nine-Item Avoidant Restrictive Food Intake Disorder Screener [NIAS]), the two-item Patient Health Questionnaire (PHQ-2), the nine-item Patient Health Questionnaire (PHQ-9), the two-item Generalised Anxiety Disorder (GAD-2), the seven-item Generalised Anxiety Disorder (GAD-7), and the KIDSCREEN-10. For adults older than 18 years, measures include the EDE-Q (or, for avoidant restrictive food intake disorder, the NIAS), the PHQ-2, the PHQ-9, the GAD-2, the GAD-7, the Clinical Impairment Assessment, and the 12-item WHO Disability Assessment Schedule 2.0. These questionnaires should be supplemented by information on patient characteristics and circumstances (ie, demographic, historical, and clinical factors). International adoption of these guidelines will allow comparison of research and clinical interventions to determine which settings and interventions work best, and for whom.

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.

Association of hospitalization for suicide attempts in adolescent girls with subsequent hospitalization for eating disorders.

OBJECTIVE: To determine the association between adolescent hospitalization for suicide attempts and the subsequent risk of eating disorder hospitalization. METHOD: This was a cohort study of 162,398 adolescent girls in Quebec, Canada, including 7741 with suicide attempts before 20 years of age, matched to 154,657 adolescents with no attempt between 1989 and 2019. The main exposure measure was suicide attempt hospitalization. The main outcome measure was hospitalization for an eating disorder up to 31 years later, including anorexia nervosa, bulimia nervosa, and other eating disorders. We used adjusted Cox regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between adolescent suicide attempts and eating disorder hospitalization. RESULTS: Adolescent girls admitted for a suicide attempt had 5.55 times the risk of eating disorder hospitalization over time (95% CI 3.74-8.23), compared with matched controls. Suicide attempt was associated with anorexia nervosa (HR 3.57, 95% CI 1.78-7.17) and bulimia nervosa and other eating disorders (HR 8.55, 95% CI 5.48-13.32). Associations were pronounced in girls with repeated suicide attempts. Girls who attempted suicide through self-poisoning had an elevated risk of anorexia nervosa, whereas girls who used violent methods such as cutting or piercing had a greater risk of bulimia nervosa and other eating disorders. Suicide attempt was strongly associated with eating disorder hospitalization in the year following the attempt, but associations persisted throughout follow-up. DISCUSSION: Suicide attempt admission is associated with the long-term risk of eating disorder hospitalization in adolescent girls. PUBLIC SIGNIFICANCE: This study of adolescent girls suggests that suicide attempt admission is associated with the long-term risk of hospitalization for eating disorders. The risk is greatest in the year after the attempt, but persists over time. Adolescents who present with a suicide attempt may benefit from screening for eating disorders and long-term follow-up to help prevent the exacerbation or development of eating disorders.

Shifting age of child eating disorder hospitalizations during the Covid-19 pandemic.

BACKGROUND: We studied the effect of the Covid-19 pandemic on child eating disorder hospitalizations in Quebec, Canada. Quebec had one of the strictest lockdown measures targeting young people in North America. METHODS: We analyzed eating disorder hospitalizations in children aged 10-19 years before and during the pandemic. We used interrupted time series regression to assess trends in the monthly number of hospitalizations for anorexia nervosa, bulimia nervosa, and other eating disorders before the pandemic (April 2006 to February 2020), and during the first (March to August 2020) and second waves (September 2020 to March 2021). We determined the types of eating disorders requiring hospital treatment and identified the age, sex and socioeconomic subgroups that were most affected. RESULTS: Hospitalization rates for eating disorders increased during the first (6.5 per 10,000) and second waves (12.8 per 10,000) compared with the period before the pandemic (5.8 per 10,000). The increase occurred for anorexia nervosa as well as other types of eating disorders. The number of girls and boys aged 10-14 years admitted for eating disorders increased during wave 1. Wave 2 triggered an increase in eating disorder admissions among girls aged 15-19 years. Hospitalization rates increased earlier for advantaged than disadvantaged youth. CONCLUSIONS: The Covid-19 pandemic affected hospitalizations for anorexia nervosa as well as other eating disorders, beginning with girls aged 10-14 years during wave 1, followed by girls aged 15-19 years during wave 2. Boys aged 10-14 years were also affected, as well as both advantaged and disadvantaged youth.

Suicide Attempts in Children Aged 10-14 Years During the First Year of the COVID-19 Pandemic.

PURPOSE: To determine if suicide attempts increased during the first year of the pandemic among young adolescents in Quebec, Canada. METHODS: We analyzed children aged 10-14 years who were hospitalized for a suicide attempt between January 2000 and March 2021. We calculated age-specific and sex-specific suicide attempt rates and the proportion of hospitalizations for suicide attempts before and during the pandemic and compared rates with patients aged 15-19 years. We used interrupted time series regression to measure changes in rates during the first (March 2020 to August 2020) and second (September 2020 to March 2021) waves and difference-in-difference analysis to determine if the pandemic had a greater impact on girls than boys. RESULTS: Suicide attempt rates decreased for children aged 10-14 years during the first wave. However, rates increased sharply during the second wave for girls, without changing for boys. Girls aged 10-14 years had an excess of 5.1 suicide attempts per 10,000 at the start of wave 2, with rates continuing to increase by 0.6 per 10,000 every month thereafter. Compared with the prepandemic period, the increase in the proportion of girls aged 10-14 years hospitalized for a suicide attempt was 2.2% greater than that of boys during wave 2. The pattern seen in girls aged 10-14 years was not present in girls aged 15-19 years. DISCUSSION: Hospitalizations for suicide attempts among girls aged 10-14 years increased considerably during the second wave of the pandemic, compared with boys and older girls. Young adolescent girls may benefit from screening and targeted interventions to address suicidal behavior.

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.

Pretreatment motivation and therapy outcomes in eating disorders: A systematic review and meta-analysis.

OBJECTIVE: Identifying modifiable predictors of outcomes following treatment for eating disorders may help to tailor interventions to patients' individual needs, improve treatment efficacy, and develop new interventions. The goal of this meta-analysis was to quantify the association between pretreatment motivation and posttreatment changes in eating disorder symptomology. METHOD: We reviewed 196 longitudinal studies reporting on change on indices of overall eating-disorder symptomatology, weight gain, binge-eating, vomiting, anxiety/depression, and treatment adherence. Meta-analyses were performed using two complementary approaches: (a) combined probability analysis using the added Z's method; (b) effect size analyses. Using random-effect models, effect sizes were pooled when there were at least three studies with the same type of statistical design and reporting statistics on the same outcome. Heterogeneity in study outcome was evaluated using Q and I2 statistics. Studies were reviewed qualitatively when the number of studies or reported data were insufficient to perform a meta-analysis. RESULTS: Forty-two articles were included. Although samples and treatments differed substantially across studies, results across studies were remarkably consistent. Both combined-probability and effect-size analyses indicated positive effects of pretreatment motivation on improvement in general eating-disorder symptoms (Cohen's r = .17), and an absence of effects on anxiety/depression symptoms. Remaining outcome indices were subject to selective reporting and/or small sample size bias. DISCUSSION: Our findings underscore the importance of incorporating treatment engagement approaches in the treatment of eating disorders. Optimal reporting of study findings and improving study quality would improve future efforts to obtain an in-depth understanding of the relationship between motivation and eating disorder symptoms.

Applying epigenetic science to the understanding of eating disorders: a promising paradigm for research and practice.

PURPOSE OF REVIEW: Studies indicate that environmental factors, acting at various moments throughout the life cycle, can result in epigenetically mediated alterations in gene expression. In this article, we review recent findings on the role of epigenetic factors in eating disorders, address methodological issues that need to be considered when interpreting research findings, and comment on possible clinical applications. RECENT FINDINGS: Evidence suggests that eating disorders implicate alterations of methylation in genes involved in the mental status, metabolism, anthropometric features and immunity. Furthermore, some research in individuals with anorexia nervosa suggests the presence of reversible, malnutrition-induced epigenetic alterations that 'reset' as patients recover. SUMMARY: Epigenetic studies in the eating disorders corroborate the idea that eating disorder cause is multifactorial, and identify markers that could help inform our understanding of illness staging and subtyping that may explain the commonly progressive course of these disorders, and that may provide insights towards the development of novel interventions. Already, there is evidence to suggest that, in people with eating disorders, epigenetically informed interventions help reduce stigma and shame, and increase self-acceptance and hopes of recovery. Although findings are intriguing, further research is required as, to date, studies apply modest sample sizes and disparate methodologies.

Severe and enduring anorexia nervosa: Update and observations about the current clinical reality.

Several objectives underlie the current article. First, to review historical diagnostic issues and clinical strategies for treating SE-AN. Second, to provide an overview of recent evidence informed strategies and clinical innovations for the treatment of SE-AN. Third, based on the authors' collective clinical and research experience, we offer eight observations that we believe capture the current clinical experience of patients with SE-AN. Some of these observations represent empirically testable hypotheses, but all are designed to generate a meaningful discussion about the treatment of this group of individuals with eating disorders. Finally, we hope to call clinicians, scientists, professional organizations, advocates, and policy makers to action to attend to critical issues related to the care of individuals with SE-AN. We believe that an international discussion could clarify areas of need for these patients and identify opportunities for clinical innovation that would enhance the lives of individuals with SE-AN and their families.

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.

Eating Disorders, Heredity and Environmental Activation: Getting Epigenetic Concepts into Practice.

Epigenetic mechanisms are believed to link environmental exposures to alterations in gene expression, and in so doing, to provide a physical substrate for the activation of hereditary potentials by life experiences. In keeping with this idea, accumulating data suggest that epigenetic processes are implicated in eating-disorder (ED) etiology. This paper reviews literature on putative links between epigenetic factors and EDs, and examines ways in which epigenetic programming of gene expression could account for gene-environment interactions acting in the EDs. The paper also presents evidence suggesting that epigenetic processes link malnutrition and life stresses (gestational, perinatal, childhood, and adult) to risk of ED development. Drawing from empirical evidence and clinical experience, we propose that an epigenetically informed understanding of ED etiology can benefit patients, caregivers, and clinicians alike, in the sense that the perspective can reduce judgmental or blameful attitudes on the part of clinicians and caregivers, and increase self-acceptance and optimism about recovery on the part of those affected.

Late and Instable Sleep Phasing is Associated With Irregular Eating Patterns in Eating Disorders.

BACKGROUND: Sleep problems are common in eating disorders (EDs). PURPOSE: We evaluated whether sleep-phasing regularity associates with the regularity of daily eating events. METHODS: ED patients (n = 29) completed hourly charts of mood and eating occasions for 2 weeks. Locomotor activity was recorded continuously by wrist actigraphy for a minimum of 10 days, and sleep was calculated based on periods of inactivity. We computed the center of daily inactivity (CenDI) as a measure of sleep phasing and consolidation of the daily inactivity (ConDI) as a measure of daily sleep rhythm strength. We assessed interday irregularities in the temporal structure of food intake using the standard deviation (SD) of frequency (IFRQ), timing (ITIM), and interval (IINT) of food intake. A self-evaluation of other characteristics included mood, anxiety, and early trauma. RESULTS: A later phasing of sleep associated with a lower frequency of eating (eating frequency with the CenDI rho = -0.49, p = .007). The phasing and rhythmic strength of sleep correlated with the degree of eating irregularity (CenDI with ITIM rho = 0.48, p = .008 and with IINT rho = 0.56, p = .002; SD of CenDI with ITIM rho = 0.47, p = .010, and SD of ConDI with IINT rho = 0.37, p = .048). Childhood Trauma Questionnaire showed associations with variation of sleep onset (rho = -0.51, p = .005) and with IFRQ (rho = 0.43, p = .023). CONCLUSIONS: Late and variable phasing of sleep associated robustly with irregular pattern of eating. Larger data sets are warranted to enable the analysis of diagnostic subgroups, current medication, and current symptomatology and to confirm the likely bidirectional association between eating pattern stability and the timing of sleep.