The United Kingdom Eating Disorders Genetics Initiative.

OBJECTIVE: The United Kingdom Eating Disorders Genetics Initiative (EDGI UK), part of the National Institute for Health and Care Research (NIHR) Mental Health BioResource, aims to deepen our understanding of the environmental and genetic etiology of eating disorders. EDGI UK launched in February 2020 and is partnered with the UK eating disorders charity, Beat. Multiple EDGI branches exist worldwide. This article serves the dual function of providing an in-depth description of our study protocol and of describing our initial sample including demographics, diagnoses, and physical and psychiatric comorbidities. METHOD: EDGI UK recruits via media and clinical services. Anyone living in England, at least 16 years old, with a lifetime probable or clinical eating disorder is eligible to sign up online: edgiuk.org. Participants complete online questionnaires, donate a saliva sample for genetic analysis, and consent to medical record linkage and recontact for future studies. RESULTS: As of September 2022, EDGI UK recruited 7435 survey participants: 98% female, 93.1% white, 97.8% cisgender, 65.9% heterosexual, and 52.1% have a university degree. Over half (57.8%) of these participants have returned their saliva DNA kit. The most common diagnoses are anorexia nervosa (48.3%), purging disorder (37.8%), bulimia nervosa (37.5%), binge-eating disorder (15.8%), and atypical anorexia nervosa (7.8%). CONCLUSION: EDGI UK is the largest UK eating disorders study and efforts to increase its diversity are underway. It offers a unique opportunity to accelerate eating disorder research. Researchers and participants with lived experience can collaborate on projects with unparalleled sample size. PUBLIC SIGNIFICANCE STATEMENT: Eating disorders are debilitating and costly for society but are under-researched due to underfunding. EDGI UK is one of the largest eating disorder studies worldwide with ongoing recruitment. The collected data constitute a resource for secondary analysis. We will combine data from all international EDGI branches and the NIHR BioResource to facilitate research that improves our understanding of eating disorders and their comorbidities.

Sociodemographic, mental health, and physical health factors associated with participation within re-contactable mental health cohorts: an investigation of the GLAD Study.

BACKGROUND: The Genetic Links to Anxiety and Depression (GLAD) Study is a large cohort of individuals with lifetime anxiety and/or depression, designed to facilitate re-contact of participants for mental health research. At the start of the pandemic, participants from three cohorts, including the GLAD Study, were invited to join the COVID-19 Psychiatry and Neurological Genetics (COPING) study to monitor mental and neurological health. However, previous research suggests that participation in longitudinal studies follows a systematic, rather than random, process, which can ultimately bias results. Therefore, this study assessed participation biases following the re-contact of GLAD Study participants. METHODS: In April 2020, all current GLAD Study participants (N = 36,770) were invited to the COPING study. Using logistic regression, we investigated whether sociodemographic, mental, and physical health characteristics were associated with participation in the COPING baseline survey (aim one). Subsequently, we used a zero-inflated negative binomial regression to examine whether these factors were also related to participation in the COPING follow-up surveys (aim two). RESULTS: For aim one, older age, female gender identity, non-binary or self-defined gender identities, having one or more physical health disorders, and providing a saliva kit for the GLAD Study were associated with an increased odds of completing the COPING baseline survey. In contrast, lower educational attainment, Asian or Asian British ethnic identity, Black or Black British ethnic identity, higher alcohol consumption at the GLAD sign-up survey, and current or ex-smoking were associated with a reduced odds. For aim two, older age, female gender, and saliva kit provision were associated with greater COPING follow-up survey completion. Lower educational attainment, higher alcohol consumption at the GLAD Study sign-up, ex-smoking, and self-reported attention deficit hyperactivity disorder had negative relationships. CONCLUSIONS: Participation biases surrounding sociodemographic and physical health characteristics were particularly evident when re-contacting the GLAD Study volunteers. Factors associated with participation may vary depending on study design. Researchers should examine the barriers and mechanisms underlying participation bias in order to combat these issues and address recruitment biases in future studies.

The network structure of mania symptoms differs between people with and without binge eating.

OBJECTIVES: People with bipolar disorder who also report binge eating have increased psychopathology and greater impairment than those without binge eating. Whether this co-occurrence is related to binge eating as a symptom or presents differently across full-syndrome eating disorders with binge eating is unclear. METHODS: We first compared networks of 13 lifetime mania symptoms in 34,226 participants from the United Kingdom's National Institute for Health and Care Research BioResource with (n = 12,104) and without (n = 22,122) lifetime binge eating. Second, in the subsample with binge eating, we compared networks of mania symptoms in participants with lifetime anorexia nervosa binge-eating/purging (n = 825), bulimia nervosa (n = 3737), and binge-eating disorder (n = 3648). RESULTS: People with binge eating endorsed every mania symptom significantly more often than those without binge eating. Within the subsample, people with bulimia nervosa most often had the highest endorsement rate of each mania symptom. We found significant differences in network parameter statistics, including network structure (M = 0.25, p = 0.001) and global strength (S = 1.84, p = 0.002) when comparing the binge eating with no binge-eating participants. However, network structure differences were sensitive to reductions in sample size and the greater density of the latter network was explained by the large proportion of participants (34%) without mania symptoms. The structure of the anorexia nervosa binge-eating/purging network differed from the bulimia nervosa network (M = 0.66, p = 0.001), but the result was unstable. CONCLUSIONS: Our results suggest that the presence and structure of mania symptoms may be more associated with binge eating as a symptom rather than any specific binge-type eating disorder. Further research with larger sample sizes is required to confirm our findings.

Genetic examination of the Mood Disorder Questionnaire and its relationship with bipolar disorder.

The Mood Disorder Questionnaire (MDQ) is a common screening tool for bipolar disorder that assesses manic symptoms. Its utility for genetic studies of mania or bipolar traits has not been fully examined. We psychometrically compared the MDQ to self-reported bipolar disorder in participants from the United Kingdom National Institute of Health and Care Research Mental Health BioResource. We conducted genome-wide association studies of manic symptom quantitative traits and symptom subgroups, derived from the MDQ items (N = 11,568-19,859). We calculated genetic correlations with bipolar disorder and other psychiatric and behavioral traits. The MDQ screener showed low positive predictive value (0.29) for self-reported bipolar disorder. Neither concurrent nor lifetime manic symptoms were genetically correlated with bipolar disorder. Lifetime manic symptoms had a highest genetic correlation (rg = 1.0) with posttraumatic stress disorder although this was not confirmed by within-cohort phenotypic correlations (rp = 0.41). Other significant genetic correlations included attention deficit hyperactivity disorder (rg = 0.69), insomnia (rg = 0.55), and major depressive disorder (rg = 0.42). Our study adds to existing literature questioning the MDQ's validity and suggests it may capture symptoms of general distress or psychopathology, rather than hypomania/mania specifically, in at-risk populations.

Risk and protective factors for new-onset binge eating, low weight, and self-harm symptoms in >35,000 individuals in the UK during the COVID-19 pandemic.

OBJECTIVE: The disruption caused by the COVID-19 pandemic has been associated with poor mental health, including increases in eating disorders and self-harm symptoms. We investigated risk and protective factors for the new onset of these symptoms during the pandemic. METHOD: Data were from the COVID-19 Psychiatry and Neurological Genetics study and the Repeated Assessment of Mental health in Pandemics Study (n = 36,715). Exposures were socio-demographic characteristics, lifetime psychiatric disorder, and COVID-related variables, including SARS-CoV-2 infection/illness with COVID-19. We identified four subsamples of participants without pre-pandemic experience of our outcomes: binge eating (n = 24,211), low weight (n = 24,364), suicidal and/or self-harm ideation (n = 18,040), and self-harm (n = 29,948). Participants reported on our outcomes at frequent intervals (fortnightly to monthly). We fitted multiple logistic regression models to identify factors associated with the new onset of our outcomes. RESULTS: Within each subsample, new onset was reported by: 21% for binge eating, 10.8% for low weight, 23.5% for suicidal and/or self-harm ideation, and 3.5% for self-harm. Shared risk factors included having a lifetime psychiatric disorder, not being in paid employment, higher pandemic worry scores, and being racially minoritized. Conversely, infection with SARS-CoV-2/illness with COVID-19 was linked to lower odds of binge eating, low weight, and suicidal and/or self-harm ideation. DISCUSSION: Overall, we detected shared risk factors that may drive the comorbidity between eating disorders and self-harm. Subgroups of individuals with these risk factors may require more frequent monitoring during future pandemics. PUBLIC SIGNIFICANCE: In a sample of 35,000 UK residents, people who had a psychiatric disorder, identified as being part of a racially minoritized group, were not in paid employment, or were more worried about the pandemic were more likely to experience binge eating, low weight, suicidal and/or self-harm ideation, and self-harm for the first time during the pandemic. People with these risk factors may need particular attention during future pandemics to enable early identification of new psychiatric symptoms.

Patient characteristics associated with retrospectively self-reported treatment outcomes following psychological therapy for anxiety or depressive disorders - a cohort of GLAD study participants.

BACKGROUND: Progress towards stratified care for anxiety and depression will require the identification of new predictors. We collected data on retrospectively self-reported therapeutic outcomes in adults who received psychological therapy in the UK in the past ten years. We aimed to replicate factors associated with traditional treatment outcome measures from the literature. METHODS: Participants were from the Genetic Links to Anxiety and Depression (GLAD) Study, a UK-based volunteer cohort study. We investigated associations between retrospectively self-reported outcomes following therapy, on a five-point scale (global rating of change; GRC) and a range of sociodemographic, clinical and therapy-related factors, using ordinal logistic regression models (n = 2890). RESULTS: Four factors were associated with therapy outcomes (adjusted odds ratios, OR). One sociodemographic factor, having university-level education, was associated with favourable outcomes (OR = 1.37, 95%CI: 1.18, 1.59). Two clinical factors, greater number of reported episodes of illness (OR = 0.95, 95%CI: 0.92, 0.97) and higher levels of personality disorder symptoms (OR = 0.89, 95%CI: 0.87, 0.91), were associated with less favourable outcomes. Finally, reported regular use of additional therapeutic activities was associated with favourable outcomes (OR = 1.39, 95%CI: 1.19, 1.63). There were no statistically significant differences between fully adjusted multivariable and unadjusted univariable odds ratios. CONCLUSION: Therapy outcome data can be collected quickly and inexpensively using retrospectively self-reported measures in large observational cohorts. Retrospectively self-reported therapy outcomes were associated with four factors previously reported in the literature. Similar data collected in larger observational cohorts may enable detection of novel associations with therapy outcomes, to generate new hypotheses, which can be followed up in prospective studies.

Comparison of symptom-based versus self-reported diagnostic measures of anxiety and depression disorders in the GLAD and COPING cohorts.

BACKGROUND: Understanding and improving outcomes for people with anxiety or depression often requires large sample sizes. To increase participation and reduce costs, such research is typically unable to utilise "gold-standard" methods to ascertain diagnoses, instead relying on remote, self-report measures. AIMS: Assess the comparability of remote diagnostic methods for anxiety and depression disorders commonly used in research. METHOD: Participants from the UK-based GLAD and COPING NBR cohorts (N = 58,400) completed an online questionnaire between 2018 and 2020. Responses to detailed symptom reports were compared to DSM-5 criteria to generate symptom-based diagnoses of major depressive disorder (MDD), generalised anxiety disorder (GAD), specific phobia, social anxiety disorder, panic disorder, and agoraphobia. Participants also self-reported any prior diagnoses from health professionals, termed self-reported diagnoses. "Any anxiety" included participants with at least one anxiety disorder. Agreement was assessed by calculating accuracy, Cohen's kappa, McNemar's chi-squared, sensitivity, and specificity. RESULTS: Agreement between diagnoses was moderate for MDD, any anxiety, and GAD, but varied by cohort. Agreement was slight to fair for the phobic disorders. Many participants with self-reported GAD did not receive a symptom-based diagnosis. In contrast, symptom-based diagnoses of the phobic disorders were more common than self-reported diagnoses. CONCLUSIONS: Agreement for MDD, any anxiety, and GAD was higher for cases in the case-enriched GLAD cohort and for controls in the general population COPING NBR cohort. For anxiety disorders, self-reported diagnoses classified most participants as having GAD, whereas symptom-based diagnoses distributed participants more evenly across the anxiety disorders. Further validation against gold standard measures is required.

Age and sex-related variability in the presentation of generalized anxiety and depression symptoms.

BACKGROUND: Generalized anxiety and depression are extremely prevalent and debilitating. There is evidence for age and sex variability in symptoms of depression, but despite comorbidity it is unclear whether this extends to anxiety symptomatology. Studies using questionnaire sum scores typically fail to address this phenotypic complexity. METHOD: We conducted exploratory and confirmatory factor analyses on Generalized Anxiety Disorder (GAD-7) and Patient Health Questionnaire (PHQ-9) items to identify latent factors of anxiety and depression in participants from the Genetic Links to Anxiety and Depression Study (N = 35,637; 16-93 years). We assessed age- and sex-related variability in latent factors and individual symptoms using multiple logistic regression. RESULTS: Four factors of mood, worry, motor, and somatic symptoms were identified (comparative fit index [CFI] = 0.99, Tucker-Lewis Index [TLI] = 0.99, root mean square error of approximation [RMSEA] = 0.07, standardized root mean square residuals [SRMR] = 0.04). Symptoms of irritability (odds ratio [OR] = 0.81) were most strongly associated with younger age, and sleep change (OR = 1.14) with older age. Males were more likely to report mood and motor symptoms (p < .001) and females to report somatic symptoms (p < .001). CONCLUSION: Significant age and sex variability suggest that classic diagnostic criteria reflect the presentation most commonly seen in younger males. This study provides avenues for diagnostic adaptation and factor-specific interventions.

Comparison of depression and anxiety symptom networks in reporters and non-reporters of lifetime trauma in two samples of differing severity.

BACKGROUND: Reported trauma is associated with differences in the course and outcomes of depression and anxiety. However, no research has explored the association between reported trauma and patterns of clinically relevant symptoms of both depression and anxiety. METHODS: We used network analysis to investigate associations between reported trauma and depression and anxiety symptom interactions in affected individuals from the Genetic Links to Anxiety and Depression (GLAD) Study (n = 17720), and population volunteers from the UK Biobank (n = 11120). Participants with current moderate symptoms of depression or anxiety were grouped into reporters and non-reporters of lifetime trauma. Networks of 16 depression and anxiety symptoms in the two groups were compared using the network comparison test. RESULTS: In the GLAD Study, networks of reporters and non-reporters of lifetime trauma did not differ on any metric. In the UK Biobank, the symptom network of reporters had significantly greater density (7.80) than the network of non-reporters (7.05). LIMITATIONS: The data collected in the GLAD Study and the UK Biobank are self-reported with validated or semi-validated questionnaires. CONCLUSIONS: Reported lifetime trauma was associated with stronger interactions between symptoms of depression and anxiety in population volunteers. Differences between reporters and non-reporters may not be observed in individuals with severe depression and/or anxiety due to limited variance in the presentation of disorder.

The Genetic Links to Anxiety and Depression (GLAD) Study: Online recruitment into the largest recontactable study of depression and anxiety.

BACKGROUND: Anxiety and depression are common, debilitating and costly. These disorders are influenced by multiple risk factors, from genes to psychological vulnerabilities and environmental stressors, but research is hampered by a lack of sufficiently large comprehensive studies. We are recruiting 40,000 individuals with lifetime depression or anxiety and broad assessment of risks to facilitate future research. METHODS: The Genetic Links to Anxiety and Depression (GLAD) Study (www.gladstudy.org.uk) recruits individuals with depression or anxiety into the NIHR Mental Health BioResource. Participants invited to join the study (via media campaigns) provide demographic, environmental and genetic data, and consent for medical record linkage and recontact. RESULTS: Online recruitment was effective; 42,531 participants consented and 27,776 completed the questionnaire by end of July 2019. Participants' questionnaire data identified very high rates of recurrent depression, severe anxiety, and comorbidity. Participants reported high rates of treatment receipt. The age profile of the sample is biased toward young adults, with higher recruitment of females and the more educated, especially at younger ages. DISCUSSION: This paper describes the study methodology and descriptive data for GLAD, which represents a large, recontactable resource that will enable future research into risks, outcomes, and treatment for anxiety and depression.