Non-suicidal self-injury among individuals with an eating disorder: A systematic review and prevalence meta-analysis.

OBJECTIVE: This study aimed to quantify the prevalence of non-suicidal self-injury across eating disorders (EDs) and within diagnostic categories through systematic review and proportional, or so-called prevalence, meta-analysis. METHOD: Included studies had to contain individuals with a verified diagnosis of an ED. The last literature search was conducted on September 11, 2023, for studies published on or before September 2023 without a restriction on earliest publication year. Results were synthesized and analyzed using the "metaprop" package in R and presented using forest plots. Bias was assessed by a Peters' regression test and funnel plot. RESULTS: 79 studies published between 1985 and 2023 were included encompassing 32,334 individuals with an ED. Importantly, 42 studies were not included in any other meta-analyses on self-injury in EDs to date. Overall prevalence of non-suicidal self-injury was 34.59% (95%CI = 30.49-38.81). Prevalence in anorexia nervosa restrictive type, binge/purge type, bulimia nervosa, binge eating disorder and other specified feeding/eating disorder were 23.19% (95%CI = 16.96-30.03%), 41.98% (95%CI = 32.35-51.91%), 36.97% (95%CI = 30.69-43.46%), 21.21% (95%CI = 14.93-28.12%) and 37.65% (95%CI = 28.59-47.09%), respectively. Prevalence estimations could not be estimated for other ED categories due to lack of a sufficient number of studies. DISCUSSION: Non-suicidal self-injury is prevalent across both binge/purge and restrictive EDs. Considering the transdiagnostic nature of self-injurious behaviors in ED, the results highlight the importance of assessment and monitoring of self-injury in people with ED, irrespective of specific diagnoses. The method of determining self-injury varied across studies and may limit this study. PUBLIC SIGNIFICANCE: This study highlights the prevalence of self-injury across eating disorders irrespective of diagnosis and within specific EDs. While diagnoses known to exhibit self-injurious behaviors (e.g., bulimia nervosa, anorexia nervosa binge/purge subtype) demonstrated the highest prevalence of self-injury, all diagnoses were found to have a prevalence greater than 20%. These findings suggest the importance of assessing and monitoring all individuals with an eating disorder for the presence of self-injury.

OBJETIVO: Este estudio tuvo como objetivo cuantificar la prevalencia de la autolesión no suicida en los trastornos de la conducta alimentaria (TCA) y dentro de las categorías diagnósticas mediante una revisión sistemática y un metaanálisis proporcional, también llamado metaanálisis de prevalencia. MÉTODO: Los estudios incluidos debían contener individuos con un diagnóstico verificado de un TCA. La última búsqueda bibliográfica se realizó el 11 de septiembre de 2023, para estudios publicados en o antes de septiembre de 2023 sin restricción en el año de publicación más temprano. Los resultados fueron sintetizados y analizados utilizando el paquete "metaprop" en R y presentados mediante gráficos de bosque. El sesgo se evaluó mediante una prueba de regresión de Peters y un gráfico de embudo. RESULTADOS: Se incluyeron 79 estudios publicados entre 1985 y 2023 que abarcaron a 32,334 individuos que padecían un TCA. Es importante destacar que 42 estudios no se incluyeron en ningún otro metaanálisis sobre autolesión en TCA hasta la fecha. La prevalencia general de la autolesión no suicida fue del 34.59% (IC del 95% = 30.49-38.81). La prevalencia en la anorexia nerviosa subtipo restrictivo, subtipo atracones/purga, bulimia nerviosa, trastorno de atracones y otros trastornos especificados de la conducta alimentaria y de la alimentación fue del 23.19% (IC del 95% = 16.96-30.03%), 41.98% (IC del 95% = 32.35-51.91%), 36.97% (IC del 95% = 30.69-43.46%), 21.21% (IC del 95% = 14.93-28.12%) y 37.65% (IC del 95% = 28.59-47.09%), respectivamente. No se pudieron estimar las estimaciones de prevalencia para otras categorías de TCA debido a la falta de un número suficiente de estudios. DISCUSIÓN: La autolesión no suicida es prevalente tanto en los TCA subtipo de atracón/purgación como en los restrictivos. Dada la naturaleza transdiagnóstica de los comportamientos autolesivos en los TCA, los resultados resaltan la importancia de la evaluación y el monitoreo de la autolesión en personas que padecen TCA, independientemente de los diagnósticos específicos. El método para determinar la autolesión varió entre los estudios y puede limitar este estudio.

Outcomes of a Virtual Day Treatment Program for Adults With Eating Disorders-Comparison With In-Person Day Treatment.

OBJECTIVE: Previous studies have indicated that virtual treatments for eating disorders (EDs) are roughly as effective as are in-person treatments; the present nonrandomized study aimed to expand on the current body of evidence by comparing outcomes from a virtual day treatment program with those of an in-person program in an adult ED sample. METHOD: Participants were 109 patients who completed at least 60% of day treatment sessions (n = 55 in-person and n = 54 virtual). Outcome measures included ED and comorbid symptoms, and motivation. RESULTS: Linear mixed models showed that global EDE-Q scores decreased during treatment (AIC = 376.396, F = 10.94, p = 0.002), irrespective of treatment modality (p = 0.186). BMI significantly increased over time (AIC = 389.029, F = 27.97, p < 0.001), with no effect of treatment modality (p = 0.779). DISCUSSION: Our findings suggest that the virtual delivery of day treatments produces comparable outcomes to those obtained using in-person formats, and that virtual formats may represent a pragmatic treatment option, especially in situations in which access to in-person care is limited.

Cortical thickness and childhood eating behaviors: differences according to sex and age, and relevance for eating disorders.

PURPOSE: This study investigated the association between childhood eating behaviors and cortical morphology, in relation to sex and age, in a community sample. METHODS: Neuroimaging data of 71 children (mean age = 9.9 ± 1.4 years; 39 boys/32 girls) were obtained from the Nathan Kline Institute-Rockland Sample. Emotional overeating, food fussiness, and emotional undereating were assessed using the Children's Eating Behavior Questionnaire. Cortical thickness was obtained at 81,924 vertices covering the entire cortex. Generalized Linear Mixed Models were used for statistical analysis. RESULTS: There was a significant effect of sex in the association between cortical thickness and emotional overeating (localized at the right postcentral and bilateral superior parietal gyri). Boys with more emotional overeating presented cortical thickening, whereas the opposite was observed in girls (p < 0.05). Different patterns of association were identified between food fussiness and cortical thickness (p < 0.05). The left rostral middle frontal gyrus displayed a positive correlation with food fussiness from 6 to 8 years, but a negative correlation from 12 to 14 years. Emotional undereating was associated with cortical thickening at the left precuneus, left middle temporal gyrus, and left insula (p < 0.05) with no effect of sex or age. CONCLUSIONS: Leveraging on a community sample, findings support distinct patterns of associations between eating behaviors and cortical thickness, depending on sex and age.

Maturation of Temporal Saccade Prediction from Childhood to Adulthood: Predictive Saccades, Reduced Pupil Size, and Blink Synchronization.

When presented with a periodic stimulus, humans spontaneously adjust their movements from reacting to predicting the timing of its arrival, but little is known about how this sensorimotor adaptation changes across development. To investigate this, we analyzed saccade behavior in 114 healthy humans (ages 6-24 years) performing the visual metronome task, who were instructed to move their eyes in time with a visual target that alternated between two known locations at a fixed rate, and we compared their behavior to performance in a random task, where target onsets were randomized across five interstimulus intervals (ISIs) and thus the timing of appearance was unknown. Saccades initiated before registration of the visual target, thus in anticipation of its appearance, were labeled predictive [saccade reaction time (SRT) < 90 ms] and saccades that were made in reaction to its appearance were labeled reactive (SRT > 90 ms). Eye-tracking behavior including saccadic metrics (e.g., peak velocity, amplitude), pupil size following saccade to target, and blink behavior all varied as a function of predicting or reacting to periodic targets. Compared with reactive saccades, predictive saccades had a lower peak velocity, a hypometric amplitude, smaller pupil size, and a reduced probability of blink occurrence before target appearance. The percentage of predictive and reactive saccades changed inversely from ages 8-16, at which they reached adult-levels of behavior. Differences in predictive saccades for fast and slow target rates are interpreted by differential maturation of cerebellar-thalamic-striatal pathways.SIGNIFICANCE STATEMENT From the first moments of life, humans are exposed to rhythm (i.e., mother's heartbeat in utero), but the timeline of brain development to promote the identification and anticipation of a rhythmic stimulus, known as temporal prediction, remains unknown. Here, we used saccade reaction time (SRT) in the visual metronome task to differentiate between temporally predictive and reactive responses to a target that alternated at a fixed rate in humans aged 6-24. Periods of age-related change varied little by target rate, with matured predictive performance evident by mid-adolescence for fast and slow rates. A strong correlation among saccade, pupil, and blink responses during target prediction provides evidence of oculomotor coordination and dampened noradrenergic neuronal activity when generating rhythmic motor responses.

Cohort profile update: The Canadian Maternal-Infant Research on Environmental Chemicals Child Development study (MIREC-CD PLUS).

BACKGROUND: The pan-Canadian Maternal-Infant Research on Environmental Chemicals (MIREC) study was established to determine whether maternal environmental chemical exposures were associated with adverse pregnancy outcomes in 2001 pregnant women. OBJECTIVES: The MIREC-Child Development (CD PLUS) study followed this cohort with the goal of assessing the potential effects of prenatal exposures on anthropometry and neurodevelopment in early childhood. POPULATION: MIREC families with children between the ages of 15 months and 5 years who had agreed to be contacted for future research (n = 1459) were invited to participate in MIREC-CD PLUS which combines data collected from an online Maternal Self-Administered Questionnaire with biomonitoring and neurodevelopment data collected from two in-person visits. PRELIMINARY RESULTS: Between April 2013 and March 2015, 803 children participated in the Biomonitoring visit where we collected anthropometric measures, blood, and urine from the children. The Behavioural Assessment System for Children-2, Behaviour Rating Inventory of Executive Function, MacArthur-Bates Communicative Development Inventories and the Communication subscale of the Adaptive Behaviour Scale from the Bayley Scales of Infant and Toddler Development-III are available on close to 900 children. There were 610 singleton children who completed in-person visits for neurodevelopment assessments including the Social Responsiveness Scale, Wechsler Preschool Primary Scale of Intelligence-III and NEuroPSYchological assessments (NEPSY). Currently, we are following the cohort into early adolescence to measure the impact of early life exposures on endocrine and metabolic function (MIREC-ENDO). CONCLUSIONS: Data collection for the MIREC-CD PLUS study is complete and analysis of the data continues. We are now extending the follow-up of the cohort into adolescence to measure the impact of early life exposures on endocrine and metabolic function (MIREC-ENDO). MIREC-CD PLUS is limited by loss to follow-up and the fact that mothers are predominately of higher socioeconomic status and 'White' ethnicity, which limits our generalizability. However, the depth of biomonitoring and clinical measures in MIREC provides a platform to examine associations of prenatal, infancy and childhood exposures with child growth and development.

Prenatal and concurrent blood mercury concentrations and associations with IQ in canadian preschool children.

BACKGROUND: Prenatal and childhood mercury (Hg) exposures have been associated with negative impacts on child neurodevelopment. It is unclear if associations persist at the low Hg exposures typical in Western countries. OBJECTIVE: To examine associations between prenatal/childhood blood Hg concentrations and child IQ in Canadian male and female children while considering the potential modifying role of prenatal fish consumption. METHODS: We analyzed data from the Maternal-Infant Research on Environmental Chemicals study. Hg was measured in first trimester (n = 527), cord (n = 430), and child (at 3-4 years of age, n = 355) blood and examined sex-stratified associations between blood Hg and children's Full Scale IQ (FSIQ), Verbal IQ (VIQ), Performance IQ (PIQ), and General Language Composite (GLC) scores (assessed with WPPSI-III). Prenatal Hg analyses were further stratified by prenatal fish consumption (low: 0-2, moderate: 3-7, or high: ≥8 times/month). RESULTS: Higher cord blood Hg concentrations were associated with lower PIQ (ß = -3.27; 95%CI: 6.44, -0.09) in male children with the lowest prenatal fish consumption. Progressively stronger positive associations were observed with PIQ in male children for moderate (ß = 1.08; 95%CI: 0.10, 2.26) and high (ß = 3.07; 95%CI: 1.95, 4.19) prenatal fish consumption. Cord blood Hg concentrations were positively associated with female children's FSIQ (ß = 1.29; 95% CI: 0.77, 1.81) and PIQ (ß = 2.01; 95% CI: 1.19, 2.83); however, when stratified only in the highest fish consumption subgroup. Among female children, higher child blood Hg concentrations were associated with an approximately 1-point increase in FSIQ, VIQ, and GLC. CONCLUSIONS: Prenatal exposure to low levels of Hg was associated with lower PIQ scores in male children with low prenatal fish intake. Positive associations between cord and child blood Hg concentrations and IQ were primarily observed in female children and may be due to beneficial effects of prenatal fish intake.

Canadian pediatric eating disorder programs and virtual care during the COVID-19 pandemic: a mixed-methods approach to understanding clinicians' perspectives.

BACKGROUND: As a result of the public health measures put in place during the COVID-19 pandemic in Canada, many health services, including those for the treatment of eating disorders, were provided at a distance. This study aims to describe the adaptations made in specialized pediatric eating disorder programs in Canada and the impact of these adaptations on health professionals' experience of providing care. METHODS: A mixed-methods design was used to survey healthcare professionals working in specialized pediatric eating disorder programs about adaptations to treatment made during the pandemic and the impact of these adaptations on their experience of providing care. Data were collected between October 2021 and March 2022 using a cross-sectional survey comprising 25 questions and via semi-structured interviews. Quantitative data were summarized using descriptive statistics and qualitative data were interpreted using qualitative content analysis. RESULTS: Eighteen healthcare professionals in Canada completed the online survey, of whom six also participated in the semi-structured interviews. The cross-sectional survey confirmed that, unlike in pre-pandemic times, the majority of participants provided medical care (15/18) and mental health care (17/18) at a distance during the pandemic, with most participants using telephone (17/18) and videoconferencing (17/18). Most (16/18) health professionals indicated that virtual care would continue to be used as a tool in pediatric ED treatment after the pandemic. Participants used a combination of virtual and in-person care, with most reporting weighing patients both in clinic (16/18) and virtually (15/18). Qualitative content analysis generated five themes: (1) responding to increased demand with insufficient resources; (2) adapting to changes in care due to the COVID-19 pandemic; (3) dealing with uncertainty and apprehension; (4) virtual care as an acceptable and useful clinical tool, and (5) optimal conditions and future expectations. Most interview participants (5/6) had globally positive views of virtual care. CONCLUSIONS: Providing virtual multidisciplinary treatment for children and adolescents with eating disorders seemed feasible and acceptable to professionals during the pandemic. Moving forward, focusing on health professionals' perspectives and providing appropriate training in virtual interventions is essential given their central role in successful implementation and continued use of virtual and hybrid care models.

Childhood Overeating and Disordered Eating From Early Adolescence to Young Adulthood: A Longitudinal Study on the Mediating Role of BMI, Victimization and Desire for Thinness.

Eating disorders have early origins, and there could be a continuum between childhood eating behaviors, such as overeating, and long-term disordered eating, but this remains to be shown. BMI, desire for thinness and peer victimization could influence this continuum, but their interactions are unknown. To fill this gap, the study used data from the Quebec Longitudinal Study of Child Development (N = 1511; 52% girls), in which 30.9% of youth presented a trajectory associated with high disordered eating from 12 to 20 years. The results support an indirect association between overeating at age 5 and disordered eating trajectories, with different mediation processes observed between boys and girls. The findings underscore the importance of promoting healthy body images and eating behaviors among youths.

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.

Implicit Affect, Heart Rate Variability, and the Metabolic Syndrome.

OBJECTIVE: Greater negative affect has been associated with an increased risk of the metabolic syndrome (METs). However, all studies to date have examined this association using explicit affect measures based on subjective ratings of emotional experiences. Prior studies suggest that implicit affect, representing the automatic, prereflective appraisal process involved in conscious emotional experiences, is associated with physiological stress responses independent of explicit affect. Furthermore, low resting heart rate variability (HRV) may increase the risk of stress-related diseases. The goals of this study were to evaluate the associations between implicit and explicit affect and METs and to assess whether these associations were amplified by lower HRV. METHODS: This secondary analysis of a larger study included 217 middle-aged women who completed measures of implicit affect, explicit affect, high-frequency HRV, and the different components of METs. RESULTS: There was a significant interaction between implicit negative affect and HRV predicting METs (odds ratio = 0.57, 95% confidence interval = 0.35-0.92), such that the combination of higher implicit affect and lower HRV was associated with a greater likelihood of METs. Similarly, there was a main effect of implicit negative affect as well as an interaction between implicit negative affect and HRV on the lipid accumulation product (b (standard error) = -0.06 (0.02), 95% confidence interval = -0.11 to -0.02), a combination of waist circumference and triglycerides. CONCLUSIONS: Higher implicit negative affect in the context of lower HRV may be related to a greater risk of METs. The present findings highlight the relevance of including implicit affect measures in psychosomatic medicine research.

Heart Rate Variability, Sleep Quality, and Depression in the Context of Chronic Stress.

BACKGROUND: Disrupted sleep quality is one of the proposed mechanisms through which chronic stress may lead to depression. However, there exist significant individual differences in sleep reactivity, which is the extent to which one experiences sleep disturbances in response to stress. PURPOSE: The aim of the current study was to investigate whether low high-frequency heart rate variability (HRV), as a psychophysiological marker of poor emotional and physiological arousal regulation, predicts stress-related sleep disturbances associated with greater risk of depression symptoms. METHODS: Using a chronic caregiving stress model, 125 mothers of adolescents with developmental disorders and 97 mothers of typically developing adolescents had their resting HRV and HRV reactivity recorded and completed a measure of depressive symptoms, as well as a 7 day sleep diary to assess their sleep quality. A moderated mediation model tested whether sleep quality mediated the association between chronic stress exposure and depressive symptoms and whether HRV moderated this mediation. RESULTS: After controlling for participant age, body mass index, ethnicity, socioeconomic status, and employment status, poor sleep quality mediated the association between chronic stress and depressive symptoms. Resting HRV moderated this indirect effect such that individuals with lower HRV were more likely to report poorer sleep quality in the context of chronic stressor exposure, which, in turn, was related to greater depressive symptoms. CONCLUSIONS: Lower HRV, a potential biomarker of increased sleep reactivity to stress, is associated with greater vulnerability to stress-related sleep disturbances, which, in turn, increases the risk for elevated depressive symptoms in response to chronic stress.

Body image-related cognitive fusion and disordered eating: the role of self-compassion and sad mood.

PURPOSE: The extent to which body image-related thoughts are endorsed and drive behaviors, a process known as Body Image-Related Cognitive Fusion (BI-CF), is an important contributor to disordered eating. Moreover, negative mood and negative self-referential processes (e.g., low self-compassion) have been reportedly associated with disordered eating; however, their associations with BI-CF are not known. The aim of this study was to investigate, among young adults, the association between (1) BI-CF and disordered eating attitudes and behaviors (2) BI-CF and self-compassion, and (3) whether sad mood influences BI-CF. METHOD: Participants completed online questionnaires that assessed BI-CF, self-compassion, negative affect, cognitive reactivity and disordered eating (N = 601). A subsample (n = 51) underwent an in-lab session in which they were exposed to a validated psychological sad mood induction task followed by the assessment of BI-CF. RESULTS: 67.8% of variation in disordered eating was accounted for by BI-CF while controlling for covariates. Self-compassion was the strongest predictor of BI-CF levels, irrespective of other eating disorder or depression risk factors (p < 0.001). Increases in sad mood did not influence levels of BI-CF. CONCLUSION: The endorsement of body image-related thoughts seems to play an important role in disordered eating. Compassionate self-responding may have positive influences on reducing negative body image-related thoughts. Furthermore, BI-CF appears to be a relatively stable phenomenon, irrespective of change in mood state. Results offer implications for the improvements in prevention and intervention models targeted towards disordered eating through self-compassion and cognitive defusion. LEVEL OF EVIDENCE: Part I: Level V, cross-sectional descriptive study. Part II: Level I, experimental study.

Birth weight is associated with adolescent brain development: A multimodal imaging study in monozygotic twins.

Previous research has shown that the prenatal environment, commonly indexed by birth weight (BW), is a predictor of morphological brain development. We previously showed in monozygotic (MZ) twins associations between BW and brain morphology that were independent of genetics. In the present study, we employed a longitudinal MZ twin design to investigate whether variations in prenatal environment (as indexed by discordance in BW) are associated with resting-state functional connectivity (rs-FC) and with structural connectivity. We focused on the limbic and default mode networks (DMNs), which are key regions for emotion regulation and internally generated thoughts, respectively. One hundred and six healthy adolescent MZ twins (53 pairs; 42% male pairs) followed longitudinally from birth underwent a magnetic resonance imaging session at age 15. Graph theoretical analysis was applied to rs-FC measures. TrackVis was used to determine track count as an indicator of structural connectivity strength. Lower BW twins had less efficient limbic network connectivity as compared to their higher BW co-twin, driven by differences in the efficiency of the right hippocampus and right amygdala. Lower BW male twins had fewer tracks connecting the right hippocampus and right amygdala as compared to their higher BW male co-twin. There were no associations between BW and the DMN. These findings highlight the possible role of unique prenatal environmental influences in the later development of efficient spontaneous limbic network connections within healthy individuals, irrespective of DNA sequence or shared environment.

Histone deacetylase 4 (HDAC4): a new player in anorexia nervosa?

Anorexia nervosa (AN) and other eating disorders continue to constitute significant challenges for individual and public health. AN is thought to develop as a result of complex interactions between environmental triggers, psychological risk factors, sociocultural influences, and genetic vulnerability. Recent research developments have highlighted a novel potentially relevant component in the AN etiology-activity of the histone deacetylase 4 (HDAC4) gene that has emerged in several recent studies related to AN. HDAC4 is a member of the ubiquitously important family of epigenetic modifier enzymes called histone deacetylases and has been implicated in processes related to the formation and function of the central nervous system (CNS), bone, muscle, and metabolism. In a family affected by eating disorders, a missense mutation in HDAC4 (A786T) was found to segregate with the illness. The relevance of this mutation in eating-related behaviors was further confirmed with mouse models. Despite  the fact that HDAC4 has not been identified as a significant signal in genome-wide association studies in AN, several studies have found significant or near-significant methylation differences in HDAC4 locus in peripheral tissues of actively ill AN patients in comparison with different control groups. Limitations of these studies include a lack of understanding of to what extent the changes in methylation are predictive of AN as such changes might also occur as a consequence of the disease. It remains to be determined how methylation in peripheral tissues correlates with that in the CNS and how different methylation patterns affect HDAC4 expression. The present review discusses the findings and potential roles of HDAC4 in AN. Its emerging roles in learning and neuroplasticity may be specific and relevant for the etiology of AN and potentially lead to novel therapeutic approaches.

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.

Body composition parameters can better predict body size dissatisfaction than body mass index in children and adolescents.

PURPOSE: Recent studies suggest that body mass index is not a reliable enough measurement for body composition in individuals, particularly in older and younger people. However, most research on body image has used the body mass index (BMI) as a physiological predictor of body satisfaction, particularly in children. The aim of this study was to investigate whether body composition is a better predictor of body size dissatisfaction in children than BMI. METHODS: This is a cross-sectional study. Healthy children and adolescents aged 5-19 years, sex male and female, were recruited using a convenience sample in Brazil. BMI was measured according to the international standardization method and body composition was measured by bioelectrical impedance analysis (BIA) with a portable device model (BIA InBodyS10 multi-frequency, USA). Body size dissatisfaction was assessed using the Kakeshita's Figure Rating Scale for Brazilian Children. Data were analyzed with logistic regression analysis. RESULTS: A total of 547 participants were evaluated, including 54% females and 67% Caucasian, with a mean age of 11.4 ± 3.8 years. The mean BMI was 20.5 ± 4.6 kg/m2, and the mean percentages of fat and lean mass were 23.01 ± 10.59% and 72.84 ± 10.03%, respectively. In the multivariable model, only body composition was significantly associated with body size dissatisfaction (odds ratio: 1.849 (1.085-3.149, p = 0.024) and 1.828 (1.043-3.202, p = 0.035), respectively). CONCLUSIONS: Body composition measures can better predict body size dissatisfaction in children and adolescents than BMI. This result may be relevant for the design of future studies on physiological indicators and body satisfaction. LEVEL OF EVIDENCE: Level V, cross-sectional study.

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.