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.

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.

"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.

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.

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.

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.

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.

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.

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.

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 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.

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.

Psychometric properties of the "Autonomous and Controlled Motivation for Treatment Questionnaire" in women with eating disorders.

OBJECTIVE: To validate the Autonomous and Controlled Motivation for Treatment Questionnaire (ACMTQ) for use in women with an eating disorder (ED). METHOD: Data were available for 463 individuals. We assessed factor structure, internal reliability, test-retest reliability, convergent/divergent validity, and incremental predictive validity. RESULTS: Our data showed acceptable fit to our hypothesized model (comparative fit index = 0.92, root mean square error of approximation = 0.09, standardized root mean square residual = 0.09). We found test-retest reliability of 0.73 for both the autonomous (α = 0.85) and controlled (α = 0.80) subscales. Autonomous scores were more strongly associated with motivation measures (ß = 0.37; 0.46) than with ED severity measures (ß = -0.10; -0.18). Associations between autonomous motivation and symptom improvement over time supported predictive validity. Controlled motivation was associated with lower motivation (ß = 0.02; -0.31) and with higher ED severity (ß = 0.12; 0.47). CONCLUSION: Our results suggest that the ACMTQ is valid for use in women with EDs and lend support to the validity of findings from previous ED studies that have used the ACMTQ.

Prognostic value of autonomous and controlled motivation in outpatient eating-disorder treatment.

According to Self-Determination Theory, when motivation to reach an objective is fully internal, it is said to be "autonomous"; when driven by external incentives, it is said to be "controlled". Previous research has indicated that autonomously motivated individuals show better response to treatments for eating disorders. OBJECTIVE: In individuals undergoing different intensities of outpatient treatment for an eating disorder, we sought to assess associations between autonomous and controlled motivations and response to treatment on the one hand, and likelihood of dropping out of treatment, on the other. METHOD: Seven hundred seventy adults meeting DSM-5 criteria for an eating disorder (216 with Anorexia Nervosa, 282 with Bulimia Nervosa, and 272 with Other Specified Feeding or Eating Disorder) were included in this study. Before an interval of outpatient treatment, individuals completed the Eating Disorder Examination Questionnaire and the Autonomous and Controlled Motivations for Treatment Questionnaire. Participants completed the Eating Disorder Examination Questionnaire again at one or two subsequent timepoints. RESULTS: After controlling for diagnosis, treatment intensity, and number of previous treatments, analyses showed that higher autonomous motivation was associated with better response on eating-disorder overall symptoms and lower likelihood of dropping out of treatment. In contrast, controlled motivation was not associated with response to treatment. DISCUSSION: Our results suggest that autonomous motivation has trans-diagnostic influence upon response to various intensities of treatment for an eating disorder. In support of an autonomy supportive approach to treatment, findings link autonomous motivation with more favorable outcome.

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.