Interplay of polygenic liability with birth-related, somatic, and psychosocial factors in anorexia nervosa risk: a nationwide study.

BACKGROUND: Although several types of risk factors for anorexia nervosa (AN) have been identified, including birth-related factors, somatic, and psychosocial risk factors, their interplay with genetic susceptibility remains unclear. Genetic and epidemiological interplay in AN risk were examined using data from Danish nationwide registers. AN polygenic risk score (PRS) and risk factor associations, confounding from AN PRS and/or parental psychiatric history on the association between the risk factors and AN risk, and interactions between AN PRS and each level of target risk factor on AN risk were estimated. METHODS: Participants were individuals born in Denmark between 1981 and 2008 including nationwide-representative data from the iPSYCH2015, and Danish AN cases from the Anorexia Nervosa Genetics Initiative and Eating Disorder Genetics Initiative cohorts. A total of 7003 individuals with AN and 45 229 individuals without a registered AN diagnosis were included. We included 22 AN risk factors from Danish registers. RESULTS: Risk factors showing association with PRS for AN included urbanicity, parental ages, genitourinary tract infection, and parental socioeconomic factors. Risk factors showed the expected association to AN risk, and this association was only slightly attenuated when adjusted for parental history of psychiatric disorders or/and for the AN PRS. The interaction analyses revealed a differential effect of AN PRS according to the level of the following risk factors: sex, maternal age, genitourinary tract infection, C-section, parental socioeconomic factors and psychiatric history. CONCLUSIONS: Our findings provide evidence for interactions between AN PRS and certain risk-factors, illustrating potential diverse risk pathways to AN diagnosis.

Study design and rationale for TEENS+REACH: Evaluating ripple effects of a family-based lifestyle intervention to untreated family members.

Background: Understanding the effects of family-based lifestyle intervention beyond the treated adolescent is important, given that obesity is a familial disease and there are likely bidirectional relations between an adolescent's treatment success and broader household changes. However, it is unknown if recommended household-wide changes are adopted or if untreated family members experience weight-related benefits. Methods: TEENS + REACH leverages our ongoing randomized clinical trial of TEENS+, a family-based lifestyle intervention for adolescents with obesity, to determine: 1) if household-wide changes to the shared home environment are implemented, 2) if ripple effects to untreated family members are observed, and 3) whether these changes are predictive of adolescents' weight management success. TEENS + REACH will expand trial assessments to include comprehensive assessments of the shared home feeding, weight, and physical activity environment of the target adolescents. Specifically, we will enroll untreated children (8-17yrs) and caregivers living in the same household as the target parent/adolescent dyad (N = 60 families). At 0, 2, 4 (primary endpoint), and 8-months, the target parent/adolescent dyad and other untreated children and caregivers in the home will complete anthropometric assessments. Discussion: Results will determine the familial reach of TEENS+ and reveal potential mediators of treatment response, which can inform future efforts to optimize family-based lifestyle interventions. Trial registration: TEENS + REACH was retrospectively registered in Clinicaltrials.gov March 22, 2023 (NCT05780970) as an observational study ancillary to the TEENS + clinical trial, registered February 22, 2019 (NCT03851796).

Differential genetic associations between dimensions of eating disorders and alcohol involvement in late adolescent twins.

BACKGROUND: Twin studies have demonstrated shared genetic and environmental effects between eating disorders and alcohol involvement in adults and middle adolescents. However, fewer studies have focused on late adolescents or investigated a wide range of eating disorder dimensions and alcohol involvement subscales in both sexes. We examined genetic and environmental correlations among three eating disorder dimensions and two alcohol involvement subscale scores in late adolescent twins using bivariate twin models. METHODS: Participants were 3568 female and 2526 male same-sex twins aged 18 years old from the Child and Adolescent Twin Study in Sweden. The Eating Disorder Inventory-2 (EDI) assessed the drive for thinness, bulimia, and body dissatisfaction. Alcohol involvement was assessed with the Alcohol Use Disorder Identification Test consumption (AUDIT-C) and problem (AUDIT-P) subscales. RESULTS: Only phenotypic and twin correlations in female twins met our threshold for twin modeling. The proportion of total variance for each trait accounted for by additive genetic factors ranged from 0.50 to 0.64 in female twins, with the rest explained by nonshared environmental factors and measurement error. Shared environmental factors played a minimal role in the variance of each trait. The strongest genetic correlation (ra ) emerged between EDI bulimia and AUDIT-P (ra = 0.46, 95% confidence interval: 0.37, 0.55), indicating that the proportion of genetic variance of one trait that was shared with the other trait was 0.21. Nonshared environmental correlations between eating disorder dimensions and alcohol involvement ranged from 0.03 to 0.13. CONCLUSIONS: We observed distinct patterns of genetic and environmental effects for co-occurring eating disorder dimensions and alcohol involvement in female vs. male twins, supporting sex-specific treatment strategies for late adolescents with comorbid eating disorders and alcohol use disorder. Our findings emphasize the importance of assessing family history of multiple eating disorder dimensions while treating late adolescents with problematic alcohol use, and vice versa, to improve detection and treatment.

The impact of genetic risk for schizophrenia on eating disorder clinical presentations.

A growing body of literature recognizes associations between eating disorders (EDs) and schizophrenia and suggests that familial liability to schizophrenia in individuals with anorexia nervosa (AN) reveals distinct patterns of clinical outcomes. To further investigate the influence of schizophrenia genetic liability among individuals with EDs, we evaluated the associations between schizophrenia polygenic risk scores (PRS) and clinical presentations of individuals with EDs including their overall health condition and ED-related symptoms. Using data from two previous studies of the genetics of EDs comprising 3,573 Anorexia Nervosa Genetics Initiative (ANGI) cases and 696 Binge Eating Genetics Initiative (BEGIN) cases born after 1973 and linked to the Swedish National Patient Register, we examined the association of schizophrenia PRS on ED clinical features, psychiatric comorbidities, and somatic and mental health burden. Among ANGI cases, higher schizophrenia PRS was statistically significantly associated with higher risk of major depressive disorder (MDD) measured by hazard ratio (HR) with 95% confidence interval (CI) (HR [95% CI]: 1.07 [1.02, 1.13]) and substance abuse disorder (SUD) (HR [95% CI]: 1.14 [1.03, 1.25]) after applying multiple testing correction. Additionally, higher schizophrenia PRS was associated with decreased clinical impairment assessment scores (-0.56, 95% CI: [-1.04, -0.08]) at the conventional significance level (p < 0.05). Further, in BEGIN cases, higher schizophrenia PRS was statistically significantly associated with earlier age at first ED symptom (-0.35 year, 95% CI: [-0.64, -0.06]), higher ED symptom scores (0.16, 95% CI: [0.04, 0.29]), higher risk of MDD (HR [95% CI]: 1.18 [1.04, 1.34]) and SUD (HR [95% CI]: 1.36 [1.07, 1.73]). Similar, but attenuated, patterns held in the subgroup of exclusively AN vs other eating disorder (OED) cases. These results suggest a similar pattern of influence of schizophrenia PRS for AN and OED cases in terms of psychiatric comorbidities, but a different pattern in terms of ED-related clinical features. The disparity of the effect of schizophrenia PRS on AN vs OED merits further investigation.

ARFID Genes and Environment (ARFID-GEN): study protocol.

BACKGROUND: The Avoidant Restrictive Food Intake Disorder - Genes and Environment (ARFID-GEN) study is a study of genetic and environmental factors that contribute to risk for developing ARFID in children and adults. METHODS: A total of 3,000 children and adults with ARFID from the United States will be included. Parents/guardians and their children with ARFID (ages 7 to 17) and adults with ARFID (ages 18 +) will complete comprehensive online consent, parent verification of child assent (when applicable), and phenotyping. Enrolled participants with ARFID will submit a saliva sample for genotyping. A genome-wide association study of ARFID will be conducted. DISCUSSION: ARFID-GEN, a large-scale genetic study of ARFID, is designed to rapidly advance the study of the genetics of eating disorders. We will explicate the genetic architecture of ARFID relative to other eating disorders and to other psychiatric, neurodevelopmental, and metabolic disorders and traits. Our goal is for ARFID to deliver "actionable" findings that can be transformed into clinically meaningful insights. TRIAL REGISTRATION: ARFID-GEN is a registered clinical trial: clinicaltrials.gov NCT05605067.

Arfid Genes and Environment (ARFID-GEN): Study Protocol.

Background: The Avoidant Restrictive Food Intake Disorder Genes and Environment (ARFID-GEN) study is a study of genetic and environmental factors that contribute to risk for developing ARFID in children and adults. Methods: A total of 3,000 children and adults with ARFID from the United States will be included. Parents/guardians and their children with ARFID (ages 7 to 17) and adults with ARFID (ages 18+) will complete comprehensive online consent, parent verification of child assent (when applicable), and phenotyping. Enrolled participants with ARFID will submit a saliva sample for genotyping. A genome-wide association study of ARFID will be conducted. Discussion: ARFID-GEN, a large-scale genetic study of ARFID, is designed to rapidly advance the study of the genetics of eating disorders. We will explicate the genetic architecture of ARFID relative to other eating disorders and to other psychiatric, neurodevelopmental, and metabolic disorders and traits. Our goal is for ARFID to deliver "actionable" findings that can be transformed into clinically meaningful insights. Trial registration: ARFID-GEN is a registered clinical trial: clinicaltrials.gov NCT05605067.

Parent involvement approach and changes in eating pathology within an adolescent obesity intervention.

BACKGROUND: Although adolescents with obesity have heightened risk for eating pathology, the impact of differential parent involvement on eating pathology after obesity treatment is unknown. We examined differences in eating pathology in adolescents whose parents were randomized to distinct interventions within adolescent obesity treatment. METHODS: Participants were 82 adolescent/parent dyads (adolescents: 63 % female; 55 % racial/ethnically marginalized) enrolled in TEENS+, a 4-month behavioral weight loss intervention. Parents were randomized to either a parent weight loss treatment (TEENS+PWL) or parent skills training (TEENS+PAC). Adolescents completed the Eating Disorder Examination-Questionnaire with Instructions (EDE-Q-I) and Child Depression Inventory (CDI) at baseline, 4 m, and 7 m. Group differences in eating pathology (global score; eating concern, weight concern, shape concern, restraint) and depression across time points were evaluated with linear mixed models. RESULTS: No significant differences were observed between TEENS+PAC and TEENS+PWL in eating pathology or depression, nor were there group by time interactions. Time point differences were observed for all EDE-Q-I and CDI outcomes, except eating concerns; pairwise contrasts revealed a variety of change patterns. Weight and shape concerns decreased from 0 to 4 m; observed reductions were maintained at 7 m. Restraint was highest at 4 m and decreased at 7 m but did not return to baseline. EDE-Q-I global scores significantly declined over time. Depression decreased over time, but a significant difference was only observed between 0 and 7 m. CONCLUSIONS: Neither parent intervention yields harm related to eating pathology in adolescents engaged in obesity treatment. Obesity treatment does not appear to have iatrogenic effects on eating pathology in adolescents.

The role of parents in behavioral treatment for adolescent obesity: design and rationale for the TEENS+ randomized clinical trial.

BACKGROUND: There is an urgent need for innovative approaches to adolescent obesity treatment, particularly among individuals from racially and ethnically marginalized backgrounds, who face increased risk of obesity and its associated morbidity and mortality. There is a particular dearth of research on the long-term efficacy of adolescent obesity treatments. Further, research and clinical practice guidelines consistently recommend parents' inclusion in their adolescents' obesity treatment, yet the most effective strategy to engage parents in adolescent obesity treatment remains unclear. Towards that end, this investigation will conduct a fully-powered, randomized clinical trial to examine the efficacy of two distinct approaches to involving parents in their adolescents' obesity treatment. METHODS: Participants will be 210 12-16 year old adolescents (body mass index [BMI]≥85th percentile) and parents (BMI≥25 kg/m2) with overweight or obesity. Dyads will be randomized to one of two 4-month treatments: 1) TEENS+Parents as Coaches (PAC), engaging parents as helpers in their child's weight management via parent skills training based on authoritative parenting, or 2) TEENS+Parent Weight Loss (PWL), engaging parents in their own behavioral weight management. All adolescents will participate in the TEENS+ protocol, which includes nutrition education with dietary goals, supervised physical activity, and behavioral support, and integrates motivational interviewing to enhance treatment engagement. Assessments of anthropometrics, dietary intake, physical activity, parenting and home environment variables will be completed at 0, 2, 4, 8, and 12 months with the primary endpoint at 12-month follow-up. DISCUSSION: Results of this investigation have the potential to significantly advance science in this area and ultimately inform clinical practice guidelines related to the role of parents in adolescent obesity treatment. TRIAL REGISTRATION: Clinicaltrials.gov NCT03851796. Registered: February 22, 2019.

Sociodemographic and clinical characteristics of treated and untreated adults with bulimia nervosa or binge-eating disorder recruited for a large-scale research study.

BACKGROUND: Eating disorders affect millions of people worldwide, but most never receive treatment. The majority of clinical research on eating disorders has focused on individuals recruited from treatment settings, which may not represent the broader population of people with eating disorders. This study aimed to identify potential differences in the characteristics of individuals with eating disorders based on whether they self-reported accessing treatment or not, in order to contribute to a better understanding of their diverse needs and experiences. METHODS: The study population included 762 community-recruited individuals (85% female, M ± SD age = 30 ± 7 years) with bulimia nervosa or binge-eating disorder (BN/BED) enrolled in the Binge Eating Genetics Initiative (BEGIN) United States study arm. Participants completed self-report surveys on demographics, treatment history, past and current eating disorder symptoms, weight history, and their current mental health and gastrointestinal symptoms. Untreated participants (n = 291, 38%) were compared with treated participants (n = 471, 62%) who self-reported accessing BN/BED treatment at some point in their lives. RESULTS: Untreated participants disproportionately self-identified as male and as a racial or ethnic minority compared with treated participants. Treated participants reported a more severe illness history, specifically, an earlier age at onset, more longstanding and frequent eating disorder symptoms over their lifetime, and greater body dissatisfaction and comorbid mental health symptoms (i.e., depression, anxiety, ADHD) at the time of the study. A history of anorexia nervosa was positively associated with treatment engagement. Individuals self-reporting a history of inpatient or residential treatment exhibited the most severe illness history, those with outpatient treatment had a less severe illness history, and untreated individuals had the mildest illness history. CONCLUSIONS: Historically overlooked and marginalized populations self-reported lower treatment access rates, while those who accessed treatment reported more severe eating disorder and comorbid mental health symptoms, which may have motivated them to seek treatment. Clinic-based recruitment samples may not represent individuals with milder symptoms or racial and ethnic diversity, and males. Community-based recruitment is crucial for improving the ability to apply research findings to broader populations and reducing disparities in medical research. Trial Registration ClinicalTrials.gov NCT04162574 ( https://clinicaltrials.gov/ct2/show/NCT04162574 ).

The majority of individuals with eating disorders never enter treatment. However, most clinical research on eating disorders recruits participants from clinics and treatment centers. Therefore, most of our knowledge about eating disorders may not represent the majority of people with eating disorders, particularly those who do not enter treatment. We studied 762 people with bulimia nervosa or binge-eating disorder recruited from the community to a large research study. We compared participants who reported never accessing treatment (38%) to participants who reported having accessed treatment at some point in their lives (62%). Untreated participants were much more likely to identify as male and as a racial or ethnic minority compared with participants who had accessed treatment (who identified mostly as female and White). Participants who had accessed treatment had a more severe illness history and higher levels of body dissatisfaction and mental health symptoms at the time of the study. The present study highlights the importance of recruiting research participants from the community to clinical studies as a way to address medical inequity in marginalized and underrepresented groups. Additionally, caution is advised when generalizing research findings from research samples who have sought treatment to all people with eating disorders.

Laxative Abuse Is Associated With a Depleted Gut Microbial Community Structure Among Women and Men With Binge-Eating Disorder or Bulimia Nervosa: The Binge Eating Genetics Initiative.

OBJECTIVE: This study assessed the associations of binge eating, compensatory behaviors, and dietary restraint with the composition and diversity of the intestinal microbiota among participants with binge-eating disorder or bulimia nervosa. METHODS: We analyzed data from 265 participants aged 18 to 45 years with current binge-eating disorder or bulimia nervosa enrolled in the Binge Eating Genetics Initiative study. We evaluated the associations of binge-eating frequency; presence/absence and frequency of vomiting, laxative use, and compulsive exercise; and dietary restraint with abundances of gut microbial genera, species, and diversity (Shannon diversity, Faith phylogenetic diversity, and Peilou's evenness) from 16S rRNA gene sequencing. General linear regression models adjusted for potential confounders, including age and current body mass index, were used to test associations; p values were corrected for the false discovery rate. RESULTS: The normalized abundance of four genus- and species-level gut microbes and three diversity indices were lower among Binge Eating Genetics Initiative participants who reported any laxative use compared with those who reported no laxative use. Vomiting frequency was positively associated with the normalized abundance of the genus Escherichia-Shigella , a potential pathobiont, although the association was attenuated to nonsignificance after adjustment for age, body mass index, and binge-eating episodes. CONCLUSIONS: Laxative use was highly and uniformly predictive of a reduced gut microbial diversity including potential commensals and pathobionts, and should be assessed and accounted for in all future studies of eating disorders and the gut microbiota. Future studies should collect data on specific medications-particularly laxatives-and dietary intake to obtain unbiased estimates of the effect of eating disorders on the gut microbiota and identify potential downstream clinical implications.Trial Registration:ClinicalTrials.gov identifier: NCT04162574 .

Risk factors for anorexia nervosa: A population-based investigation of sex differences in polygenic risk and early life exposures.

OBJECTIVE: To examine sex differences in risk factors for anorexia nervosa (AN). METHOD: This population-based study involved 44,743 individuals (6,239 AN cases including 5,818 females and 421 males, and 38,504 controls including 18,818 females and 19,686 males) born in Denmark between May 1981 and December 2009. Follow-up began on the individual's sixth birthday and ended at AN diagnosis, emigration, death, or December 31, 2016, whichever occurred first. Exposures included socioeconomic status (SES), pregnancy, birth, and early childhood factors based on data from Danish registers, and psychiatric and metabolic polygenic risk scores (PRS) based on genetic data. Hazard ratios were estimated using weighted Cox proportional hazards models stratified by sex (assigned at birth), with AN diagnosis as the outcome. RESULTS: The effects of early life exposures and PRS on AN risk were comparable between females and males. Although we observed some differences in the magnitude and direction of effects, there were no significant interactions between sex and SES, pregnancy, birth, or early childhood exposures. The effects of most PRS on AN risk were highly similar between the sexes. We observed significant sex-specific effects of parental psychiatric history and body mass index PRS, though these effects did not survive corrections for multiple comparisons. CONCLUSIONS: Risk factors for AN are comparable between females and males. Collaboration across countries with large registers is needed to further investigate sex-specific effects of genetic, biological, and environmental exposures on AN risk, including exposures in later childhood and adolescence as well as the additive effects of exposures. PUBLIC SIGNIFICANCE: Sex differences in the prevalence and clinical presentation of AN warrant examination of sex-specific risk factors. This population-based study indicates that the effects of polygenic risk and early life exposures on AN risk are comparable between females and males. Collaboration between countries with large registers is needed to further investigate sex-specific AN risk factors and improve early identification of AN.

Course and predictors of eating disorder symptoms, anxiety symptoms, and pandemic-related eating disorder concerns among adults with eating disorders during the first year of the COVID-19 pandemic.

OBJECTIVE: The COVID-19 pandemic and public health mitigation measures have negatively impacted individuals with eating disorders (ED). We evaluated changes in and predictors of ED symptoms, pandemic-related ED concerns, and anxiety symptoms across the first 12 months of the COVID-19 pandemic among individuals with self-reported EDs in the United States (US), Sweden (SE), and the Netherlands (NL). METHOD: Participants in the US (N = 510), SE (N = 982), and NL (N = 510) completed an online survey assessing ED symptoms (binge eating, restriction, compensatory behaviors, and anxiety about being unable to exercise), general anxiety symptoms, and pandemic-related ED concerns about accessing food, lack of structure and social support, being in a triggering environment, and food and treatment costs. In the US and NL, respondents completed surveys beginning April 2020 and continuing monthly for a year. In SE, respondents completed baseline surveys in May 2020, a six-month follow-up around December 2020, and a 12-month follow-up in May 2021. RESULTS: Three patterns emerged: (1) a curvilinear course with the highest level of symptoms at baseline, declining through November 2020, and increasing through the rest of the year; (2) a linear declining course over time; and (3) a stable course with no changes. Worries about COVID-19 infection, lockdown, concerns about lack of structure and social support, and concerns about accessing food consistent with one's recovery meal plan predicted increases in ED symptoms. DISCUSSION: ED symptoms tracked with pandemic-related concerns in people with EDs. Conceptualizing predictors of symptoms may inform therapy and public health resources that reduce the impact of pandemics on mental health. PUBLIC SIGNIFICANCE: Our findings suggest that the COVID-19 pandemic had negative impacts on people with eating disorders, including amplification of mental health symptoms and stressors around peak periods of infection and COVID-19 restrictions. These findings inform medical providers, policy-makers, and community-based supports about the information and resource needs of this group to ensure efficient dissemination in future public health emergencies and during the ongoing COVID-19 pandemic.

Binge-eating disorder with and without lifetime anorexia nervosa: A comparison of sociodemographic and clinical features.

OBJECTIVE: To compare individuals who have experienced binge-eating disorder (BED) and anorexia nervosa (AN) (BED AN+) to those who have experienced BED and not AN (BED AN-). METHOD: Participants (N = 898) met criteria for lifetime BED and reported current binge eating. Approximately 14% had a lifetime diagnosis of AN. Analyses compared BED AN+ and BED AN- on sociodemographic variables and clinical history. RESULTS: The presence of lifetime AN was associated with more severe eating disorder symptoms, including earlier onset, more frequent, more chronic, and more types of eating disorder behaviors over the lifetime, as well as a higher lifetime prevalence of bulimia nervosa (BN). Participants with lifetime AN reported being more likely to have received treatments for BED or BN, had significantly lower minimum, current, and maximum BMIs, had more severe general anxiety, and were significantly more likely to be younger and female. In the full sample, the lifetime prevalence of unhealthy weight control behaviors was high and treatment utilization was low, despite an average 15-year history since symptom onset. Gastrointestinal disorders and comorbid anxiety, depression, and attention-deficit/hyperactivity disorder symptoms were prevalent. DISCUSSION: Individuals fared poorly on a wide array of domains, yet those with lifetime AN fared considerably more poorly. All patients with BED should be screened for mental health and gastrointestinal comorbidities and offered referral and treatment options. PUBLIC SIGNIFICANCE: Individuals experiencing binge-eating disorder have severe symptomology, but those who have experienced binge-eating disorder and anorexia nervosa fare even more poorly. Our study emphasizes that patients with binge-eating disorder would benefit from being screened for mental health and gastrointestinal comorbidities, and clinicians should consider history of unhealthy weight control behaviors to inform treatment and relapse prevention.

Perceptions and experiences with eating disorder treatment in the first year of COVID-19: A longitudinal qualitative analysis.

OBJECTIVE: The COVID-19 pandemic created significant challenges in accessing and receiving treatment for individuals with eating disorders (EDs). The purpose of this study is to explore perceptions of and experiences with ED treatment during the first year of the pandemic among individuals with past and self-reported EDs in the United States. METHODS: Online surveys were administered to adults (N = 510) with a past or current self-reported ED at 13 timepoints between April 2020 and May 2021. Using longitudinal qualitative analysis, 5651 free-text responses were examined to capture experiences with ED treatment and generate inferences of change over time. RESULTS: We categorized results into four sequential, temporal quarters and identified patterns that explained participants' perceptions of facilitators, barriers, and experiences with ED treatment over time: Quarter 1. Treatment Disruption and Reorienting Recovery; Quarter 2. Accumulating COVID-19 Stress and Virtual Treatment Woes; Quarter 3. A Continuation of Inadequate Care; and Quarter 4. Ongoing Adaptation and Adjustment to Uncertainty. Participant experiences were marked by numerous barriers to accessing care, challenges adjusting to virtual treatment, unmet treatment needs, and beginning acceptance of telehealth. DISCUSSION: Our findings present a timeline to help evaluate challenges related to navigating the switch to virtual care which created significant disruption to ED recovery. Participants spent much of the first year trying to adjust to unemployment, loss of insurance, and lack of access to in-person treatment. Future research should identify additional strategies to improve the receipt and experience of care for EDs. PUBLIC SIGNIFICANCE: Our findings suggest that individuals with eating disorders were significantly challenged by accumulating COVID-19 stress, worsening symptomatology, and limited access to effective treatment during the first year of the pandemic. This knowledge can guide clinicians, treatment centers, and policy makers in addressing the behavioral health needs of individuals impacted by disordered eating amidst emergent public health crises.

Longer-term impact of COVID-19 among individuals with self-reported eating disorders in the United States, the Netherlands, and Sweden.

OBJECTIVE: We assessed eating disorder (ED) illness status, symptomatology, treatment access, anxiety, and depression in the first year of the COVID-19 pandemic among individuals with a pre-existing ED in the United States (US), the Netherlands (NL), and Sweden (SE). METHODS: Participants completed online surveys in April-July 2020, at the early stage of the pandemic, and one year later. At one-year follow-up, we added questions addressing retrospective changes in ED symptoms, treatment, and anxiety/depression since the start of the COVID-19 pandemic. We present descriptive statistics and assess change in ED symptomatology, treatment, and anxiety/depression among those with an active or lingering ED. RESULTS: Participants (US n = 132; NL n = 219; SE n = 702) were mostly young and female with a history of anorexia nervosa (>60% in all three countries). Across countries, respondents reported impact of COVID-19 on ED symptoms at both time points, with improvement in US and NL at one-year follow-up, and stable but less impact on ED symptoms in SE. Furthermore, at one-year follow-up, roughly half of those in treatment reported reduced treatment access and quality, and the majority of the sample reported increased anxiety and depressive mood since the start of the pandemic. DISCUSSION: Our findings suggest that the self-perceived impact of COVID-19 changed over time but remained concerning even one year after the start of the pandemic. Clinicians, community organizations, and policy makers are encouraged to address potentially changing treatment needs in the face of public health emergency events. PUBLIC SIGNIFICANCE: Our findings suggest that the impact of COVID-19 on individuals with eating disorders decreased over time but remained concerning even one year after the start of the pandemic and that the impact differed across countries. Clinicians, community organizations, and policy makers are encouraged to incorporate this knowledge to address potentially changing treatment needs in the face of public health emergency events.

Associations Between Attention Deficit Hyperactivity Disorder Symptom Dimensions and Disordered Eating Symptoms in Adolescence: A Population-Based Twin Study.

Although bivariate associations between attention-deficit/hyperactivity disorder (ADHD) and eating disorders in adolescent girls and boys have been previously identified, the mechanistic link underlying the symptom-level associations remains unclear. We evaluated shared genetic and environmental influences on ADHD symptoms and disordered eating in 819 female and 756 male twins from the Swedish TCHAD cohort using bivariate models. Common additive genetic and unique environmental effects accounted for majority of ADHD and disordered eating associations in a differential manner. For girls, the strongest genetic correlation was observed for cognitive/inattention problems-bulimia (0.54), with genetic factors accounting for 67% of the phenotypic correlation. For boys, the strongest genetic correlations were observed for conduct problems-bulimia and hyperactivity-bulimia (~ 0.54), accounting for 83% and 95% of the phenotypic correlation, respectively. As per our findings, the risk of comorbidity and shared genetics highlights the need for preventative measures and specialized treatment for ADHD and disordered eating in both sexes.

Mapping anorexia nervosa genes to clinical phenotypes.

BACKGROUND: Anorexia nervosa (AN) is a psychiatric disorder with complex etiology, with a significant portion of disease risk imparted by genetics. Traditional genome-wide association studies (GWAS) produce principal evidence for the association of genetic variants with disease. Transcriptomic imputation (TI) allows for the translation of those variants into regulatory mechanisms, which can then be used to assess the functional outcome of genetically regulated gene expression (GReX) in a broader setting through the use of phenome-wide association studies (pheWASs) in large and diverse clinical biobank populations with electronic health record phenotypes. METHODS: Here, we applied TI using S-PrediXcan to translate the most recent PGC-ED AN GWAS findings into AN-GReX. For significant genes, we imputed AN-GReX in the Mount Sinai BioMe™ Biobank and performed pheWASs on over 2000 outcomes to test the clinical consequences of aberrant expression of these genes. We performed a secondary analysis to assess the impact of body mass index (BMI) and sex on AN-GReX clinical associations. RESULTS: Our S-PrediXcan analysis identified 53 genes associated with AN, including what is, to our knowledge, the first-genetic association of AN with the major histocompatibility complex. AN-GReX was associated with autoimmune, metabolic, and gastrointestinal diagnoses in our biobank cohort, as well as measures of cholesterol, medications, substance use, and pain. Additionally, our analyses showed moderation of AN-GReX associations with measures of cholesterol and substance use by BMI, and moderation of AN-GReX associations with celiac disease by sex. CONCLUSIONS: Our BMI-stratified results provide potential avenues of functional mechanism for AN-genes to investigate further.

Design and rationale for evaluating the impact of salad bars on elementary school students' fruit, vegetable, and energy intake: a wait list control, cluster randomized controlled trial.

BACKGROUND: Most children do not consume the recommended amount of fruit and vegetable (FV) servings. Changing the school food environment can be a cost-efficient, effective approach to improving children's dietary quality. There is great popular support for school salad bars as a means to increase children's FV intake within the National School Lunch Program (NSLP), yet empirical research is limited. Further, although FV consumption can facilitate healthy weight management if these foods replace high calorie items, there is a need to enhance understanding of salad bars' influence on children's diet quality and energy intake within the NSLP. This is particularly important to investigate in schools in communities characterized by high poverty, as students they serve are particularly likely to rely on school meals. METHODS: This report describes the design and rationale of a federally-funded investigation that uses validated methods to evaluate school salad bars. This district plans to install salad bars into 141 elementary schools over 5-years, facilitating the conduct of a waitlist control, cluster randomized controlled trial. Specifically, 12 pairs of matched schools will be randomly selected: half receiving a salad bar (Intervention) and half serving pre-portioned FVs only, standard under the NSLP (Control). Thus, groups will have different FV presentation methods; however, all schools will operate under a policy requiring students to take at least one FV serving. Schools will be matched on Title I status and percent of racial/ethnic minoritized students. Intake will be objectively assessed at lunch in each school pair, prior to (baseline), and 4-6 weeks after salad bars are installed (post), yielding ~ 14,160 lunch observations throughout the study duration. Cafeteria sales and NSLP participation data will be obtained to determine how salad bars impact revenues. Finally, implementation factors and cafeteria personnel's perspectives will be assessed, to identify barriers and facilitators to salad bars use and inform sustainability efforts. Proposed methods and current status of this investigation due to COVID-19 are described. DISCUSSION: Results will have great potential to inform school nutrition policies and programs designed to improve dietary quality and reduce obesity. TRIAL REGISTRATION: Retrospectively registered (10/28/22) in clinicaltrials.gov (NCT05605483).

Reproducible changes in the anorexia nervosa gut microbiota following inpatient therapy remain distinct from non-eating disorder controls.

The composition of the gut microbiota in patients with anorexia nervosa (AN), and the ability of this microbial community to influence the host, remains uncertain. To achieve a broader understanding of the role of the intestinal microbiota in patients with AN, we collected fecal samples before and following clinical treatment at two geographically distinct eating disorder units (Center of Excellence for Eating Disorders [UNC-CH] and ACUTE Center for Eating Disorders [Denver Health]). Gut microbiotas were characterized in patients with AN, before and after inpatient treatment, and in non-eating disorder (non-ED) controls using shotgun metagenomic sequencing. The impact of inpatient treatment on the AN gut microbiota was remarkably consistent between eating disorder units. Although weight in patients with AN showed improvements, AN microbiotas post-treatment remained distinct from non-ED controls. Additionally, AN gut microbiotas prior to treatment exhibited more fermentation pathways and a lower ability to degrade carbohydrates than non-ED controls. As the intestinal microbiota can influence nutrient metabolism, our data highlight the complex microbial communities in patients with AN as an element needing further attention post inpatient treatment. Additionally, this study defines the effects of renourishment on the AN gut microbiota and serves as a platform to develop precision nutrition approaches to potentially mitigate impediments to recovery.

Common Genetic Variation and Age of Onset of Anorexia Nervosa.

Background: Genetics and biology may influence the age of onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to age of onset of AN and to investigate the genetic associations between age of onset of AN and age at menarche. Methods: A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed, which included 9335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age of onset, early-onset AN (<13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses. Results: Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (single nucleotide polymorphism-h 2) were 0.01-0.04 for age of onset, 0.16-0.25 for early-onset AN, and 0.17-0.25 for typical-onset AN. Early- and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age of onset and early-onset AN estimated from independent GWASs significantly predicted age of onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early-onset AN. Conclusions: Our results provide evidence consistent with a common variant genetic basis for age of onset and implicate biological pathways regulating menarche and reproduction.