Gaining a Holistic Understanding of Eating Disorders: Phenotyping and Genotyping Illness

The Holistic Understanding Study is a longitudinal, multi-site, biopsychosocial phenotyping and genotyping study designed to clarify the multi-level mechanisms underpinning eating disorders (EDs), including Anorexia Nervosa (AN), Bulimia Nervosa (BN), Binge Eating Disorder (BED), Avoidant/Restrictive Food Intake Disorder (ARFID), and Other Specified Feeding or Eating Disorder (OSFED). The rationale is grounded in the limited effectiveness of current evidence-based treatments and high relapse rates, suggesting that existing models insufficiently capture the complexity of EDs. This study seeks to generate a comprehensive and integrated understanding of illness trajectory, driving and maintenance mechanisms, and individual treatment targets by collecting extensive behavioural, cognitive, neurobiological, genomic, and psychosocial data. Participants aged 14 years and older are recruited through national ED networks, clinical services, and digital platforms. Following screening, eligible participants complete a structured assessment protocol across four timepoints: baseline (T1), 12 weeks (T2), 26 weeks (T3), and 52 weeks (T4). There will be 4 assessments conducted on separate days and completed within 7 days: (1) a two-hour online psychometric survey administered via REDCap comprising validated measures of ED symptomatology, identity, quality of life, psychopathology, and interoception, and The Self-Referential Memory Paradigm and the Connectedness: Sense of Commitment Paradigm tasks administered via Qualtrics hosted by The University of Sydney; (2) a 2 hour and 40-minute semi-structured clinical interview via Zoom, including the Eating Disorder Examination (EDE) with EDE ARFID module, Mini International Neuropsychiatric Interview (MINI), and Occupational Performance History Interview; (3) a 1.5-hour online psychometric survey administered via REDCap comprising validated measures of impulsivity, emotion regulation, and social cognition, and a Cognitive Impulsivity Suite administered via an existing platform hosted by Monash University of gamified assessment of three constructs important for understanding different processes underlying cognitive impulsivity including attentional control, information gathering, and monitoring/shifting; and (4) a three-hour in-person assessment involving collection of biological samples (blood, faeces), anthropometric and physiological measurements (weight, height, blood pressure), functional and structural MRI (including a food-choice task). Participants will be asked to wear a smart watch to measure sleep, activity, heart rate, and stress for 26 weeks. A total 420 ‘full participants’ will complete assessments 1-4. This cohort will be selected to ensure a representative range of eating disorder diagnostic categories: Anorexia Nervosa (AN) – 56, Bulimia Nervosa (BN) – 102, Binge Eating Disorder (BED) – 102, Avoidant/Restrictive Food Intake Disorder (ARFID) – 30, Anorexia Nervosa in adults (AN adult) – 30, and Other Specified Feeding or Eating Disorder (OSFED) including Atypical Anorexia Nervosa (Atypical AN) – 100. Participants must be ‘full participants’ of the Holistic Understanding study to be eligible for a companion clinical trial for AN, OSFED Atypical AN, BN or BED. Eligible participants will be offered enrolment in a companion clinical trial. A total 256 ‘partial participants’ will complete assessment 1-3 only. Additional ‘eCohort participants’ beyond the minimum target of 676 will complete an abbreviated form of the study that is available fully online, including assessments 1 and 2 only. A modified assessment protocol will be implemented at T1, T2, T3 and T4 depending on the timepoint and whether the participant is a full, partial or eCohort participant. All assessments are standardised and delivered individually via a hybrid model: online (REDCap), remote (Zoom/telephone), and in-person across three academic and clinical sites in NSW and Victoria. Research staff conducting interviews and sample collection are trained in assessment delivery, risk management, and biosafety procedures. Biological samples are stored and processed at a central laboratory, with blood analysed for hormonal, metabolic and inflammatory markers, and genomic data used for genomic wide association studies (GWAS) and polygenic risk score estimation. MRI data are collected using a 3T Siemens Prisma scanner and include structural, resting-state, and task-based fMRI sequences. Data from this study will inform precision medicine approaches by enabling multivariate modelling (e.g., cluster analysis, network modelling) of latent traits and illness subtypes across ED diagnoses. The study also supports companion clinical trials by providing a detailed characterisation of participants for personalised treatment allocation, and exploration of mechanisms of change. The companion clinical trials (not covered in this registration form) include 1) A Sequential Multiple Assignment Randomised Trial (SMART) of personalised treatment for Bulimia Nervosa and Binge Eating Disorder (protocol number: X24-0273), and 2) For Me Trial: A Pragmatic N-of-1 Multiple Baseline Single-Case Experimental Design (SCED) Study to Evaluate a Personalised Package of Care for Young People with Anorexia Nervosa and their Carers (protocol number: X24-0243).