A Longitudinal Study of Severe and Enduring Eating Disorders
- Conditions
- Eating DisordersAnorexia NervosaBulimia NervosaBinge Eating DisorderOther Specified Feeding or Eating Disorder
- Registration Number
- NCT06752304
- Lead Sponsor
- Uppsala University Hospital
- Brief Summary
The goal of this observational longitudinal study is to investigate characteristics and factors associated with the development of Severe and Enduring Eating Disorders (SEED). In this project, the researchers will follow two prospective cohorts of patients with eating disorders (ED), one adolescent (ages 14-17) and one adult (ages 18+), in terms of change in and impact of clinical, psychological, and biological risk factors.
Data will be collected at baseline, after treatment, two years after baseline, and thereafter five, 10 and 20 years after baseline. Participants will be asked to undergo a physical examination, leave blood samples, be interviewed, and fill in questionnaires. If the participants are minors, their care takers will also fill in the questionnaires.
The study aims to explore how clinical, psychological, and biological risk factors-including comorbidity, personality characteristics, difficulties with emotion regulation (ER), cognitive inflexibility, loneliness, severe ED symptoms, and inflammatory activation-contribute to a chronic course of the disorder.
- Detailed Description
BACKGROUND, AIMS AND HYPOTHESES
Eating disorders (EDs) are psychiatric conditions characterized by a loss of control over food intake. The prevalence of anorexia nervosa (AN) is estimated at approximately 1-2%, while bulimia nervosa (BN) affects 2-3% of the population. EDs significantly impair functioning, have serious health consequences, and are associated with high mortality rates. Around 20% of patients with AN and 10% of those with BN develop a long-lasting illness, often referred to as Severe and Enduring Eating Disorders (SEED). While there is no scientific consensus on the definition of SEED, it is frequently defined as a duration of illness lasting seven years or more. Research suggests that factors maintaining EDs may differ from those that trigger them.
The underlying causes of EDs remain largely unknown, though their origins are considered multifactorial. Psychiatric comorbidities are highly prevalent in EDs, significantly influencing their course and outcomes. Personality disorders (PDs) are associated with poorer treatment outcomes for EDs, but longitudinal studies examining the trajectory of PDs in EDs are limited, and findings are inconsistent.
Dysfunctional emotion regulation (ER) has been identified as a transdiagnostic psychological risk factor for many psychiatric disorders, including EDs. ER difficulties can manifest as undercontrol, characterized by personality traits such as impulsivity and insufficient self-control, or overcontrol, characterized by emotional inhibition and excessive self-control och cognitive inflexibility. Some models propose that undercontrol is central to BN, while overcontrol are core features of AN. However, the course and stability of ER in EDs remain poorly understood due to a lack of longitudinal studies.
Another understudied factor in EDs is loneliness, encompassing perceived social isolation and a lack of connectedness. Loneliness has been linked to ER strategies, such as excessive self-control and emotional avoidance, which in youth can contribute to social isolation, reduced life satisfaction, and a higher risk of enduring mental health problems. The role of loneliness in SEED, however, is not well understood.
Further, research on EDs has proposed that biological factors, including dysregulation of the immune system, plays a role in the development and maintenance of the EDs. Studies indicate a pro-inflammatory state in AN, though it remains unclear whether this is a state or trait marker. The role of inflammation in BN is even less understood, and studies present mixed findings. Some evidence suggests an increased risk of BN in individuals with autoimmune or inflammatory diseases, highlighting the need for further investigation into inflammatory markers over the course of the illness.
In summary, clinical factors such as psychiatric comorbidity and personality disorders; psychological factors including personality characteristics, dysfunctional emotion regulation, overcontrol/undercontrol, cognitive inflexibility, loneliness, and severe eating disorder (ED) symptoms; and biological factors such as immune system dysregulation may all play a role in the development, maintenance, and relapse of EDs. However, research in this field is scarce.
This projects aims is to increase our knowledge about risk factors for a severe course in EDs. Our overarching research question is: What are the key clinical, psychological, and biological risk factors of a severe and enduring course of an eating disorder?
It is hypothesized that a chronic course of ED is related to severe ED symptoms, personality traits related to maladaptive over- and undercontrol, difficulties with emotion regulation (ER), and increased systemic inflammation.
Primary outcomes are
* eating disorder diagnosis at follow-up
* severity of eating disorder symptoms
Secondary outcomes are
* psychosocial impairment
* quality of life
* loneliness at follow-up
* comorbidity at follow-up
* systemic inflammatory activity at follow-up
* Physical status at follow-up
Predictors, moderators and mediators
* emotion regulation
* personality
* cognitive flexibility
* loneliness at baseline
* comorbidity at baseline
* systemic inflammatory activity at baseline
* duration of illness
* time in treatment
* motivation for change
* treatment completion/treatment dropout
* Physical status at baseline
PROCEDURE
Two prospective cohorts of patients with eating disorders (EDs)-one adolescent and one adult-will be followed longitudinally to examine changes in and the impact of clinical factors, personality traits, emotion regulation (ER) difficulties, loneliness, and biomarkers. Data will be collected at baseline, post-treatment, two years post-baseline, and at five, 10, and 20 years. Participants will be recruited consecutively from autumn 2024 onwards from the Eating Disorder Unit at the Uppsala Department of Child and Adolescent Psychiatry (ED-CAP) and the eating disorder unit for adults (ED-P).
Child and adolescent psychiatry (ED-CAP)
The eating disorder unit at the Department of Child and Adolescent Psychiatry at Uppsala University Hospital (CAP) treats patients with AN, BN, Other Specified Feeding or Eating Disorder (OSFED), and Avoidant Restrictive Food Intake Disorder (ARFID) up to 18 years. Patients are referred to the unit either by other healthcare professionals or by themselves and/or their parents.
All patients are systematically assessed using a structure implemented by Swedish ED clinics that provides valid data to the national quality register. The structure consists of an assessment of clinical history, diagnostic evaluation with the child and adolescent version of the MINI International Neuropsychiatric Interview for Children and Adolescents (MINI-KID) or Electronic Psychiatric Screening Interview for children (EPSI-C), the Eating Disorder Examination interview (EDE-I), and clinician rating of symptoms and functioning (C-GAS) and the Clinical Global Impressions scale (CGI). In addition, weight and height are measured, and self-ratings with the Eating Disorder Examination Questionnaire (EDE-Q), Clinical Impairment Assessment Questionnaire (CIA), and Montgomery-Åsberg Depression Rating Scale Self-Assessment (MADRS-S) are collected.
After this initial assessment, all patients will be invited to participate in research. A research nurse will invite all patients and perform the initial somatic examination as well as sampling of blood. The patients who accept participation will sign informed consent to be included in the study. Since the youths are at least 14 years old, their parents/caregivers will also be required to accept participation and sign informed consent. Participants will receive questionnaires sent to them digitally.
The eating disorder clinic for adults (ED-P)
The eating disorder clinic for adults at the Department of Psychiatry at Uppsala University Hospital (ED-P) treats adults (≥ 18 years) with EDs. The clinic receives referrals from healthcare professionals (mainly physicians or psychologists) from other parts of the regional healthcare system. Patients can also refer themselves.
All patients undergo a systematic evaluation upon arrival at the eating disorder clinic. This consists of a clinical history and a structured diagnostic interview; either the MINI for DSM-5 or the Structured Clinical Interview for DSM-5 Axis I Disorders - Clinical Version (SCID-I CV). Patients also undergo the Eating Disorder Examination interview (EDE-I) and complete the self-report instruments Eating Disorder Examination Questionnaire (EDE-Q), Clinical Impairment Assessment Questionnaire (CIA), and Montgomery-Åsberg Depression Rating Scale Self-assessment (MADRS-S). Weight and height are measured.
All diagnostic assessments at the Department of Psychiatry are conducted by psychologists or physicians who have received training in the procedure. Patients who, during the assessment, are diagnosed with AN, BN, BED, ARFID, or OSFED of moderate to severe intensity, or OSFED with psychiatric comorbidity, and who accept treatment are accepted for treatment at P-ED. Patients who are diagnosed with mild OSFED or moderate OSFED without psychiatric comorbidity are referred to primary care for monitoring or treatment.
After this initial assessment, all patients will be invited to participate in research. An appointed person will invite all patients. If the patient accepts participation, they will sign an informed consent form. Participants will receive questionnaires sent to them digitally.
All Ages: Both ED-CAP and ED-P Participants will be asked about the collection of biomarkers through Uppsala Psychiatric Patient samples (UPP) (ethics approval Dnr 2012/081), which is an infrastructure for the collection of biological materials at the Department of Psychiatry at Uppsala University Hospital. All patients will be invited to participate in UPP, and inflammatory markers will be analyzed in accordance with the informed consent for UPP. Inflammatory markers will be analyzed from venous blood samples drawn from participants before treatment, immediately after treatment or dropout, and at the two-year follow-up.
At baseline, the following data will be collected: Diagnoses, physical examination (BMI, pulse, blood pressure), demographic characteristics, clinical characteristics, personality traits, psychological risk factors (e.g., ER difficulties, including loneliness), and biomarkers (including markers of inflammation). The same procedure will be repeated again after two years. A few questionnaires will be distributed at treatment termination or dropout.
After five, 10, and 20 years, patients will be followed up through National Helath registers and with questionnaires. Weighing will be performed weekly during treatment and at the follow-up two years later. At all time points, questionnaires will be distributed digitally. Process measures, such as the type of received treatment, number of treatment sessions, whether the patient dropped out or completed treatment, will be monitored. At follow-up, participants will be asked to answer a set of questions regarding, for example, living conditions, in addition to the questionnaires assessed at baseline.
QUALITY ASSURANCE PLAN
Interviewers will be trained and quality assured by calculating inter-rater agreement. For self-assessment, well established psychometrically evaluated instruments have been chosen. Special consideration has been given to selecting instruments suitable for both adolescents and adults.
SAMPLE SIZE ASSESSMENT
Sample size calculations were performed to ensure adequate power for the proposed analyses. With a Cohens effect size of d = 0.2, 199 participants will be required in each group, given an alpha of 0.05 and a power of 0.8. Dropout over time is expected, which increases as more time passes, estimating a 50% dropout by the final physical follow-up. Therefore, just under 400 participants need to be included in each group in order to have sufficient data for the last follow-up.
DATA ANALYSES
A range of statistical techniques will be employed to address the hypotheses and research aims, considering the longitudinal design, comparisons between the adolescent and adult cohorts, and diversity of outcome variables:
Descriptive analyses - Descriptive statistics (means, standard deviations, proportions) will summarize demographic, clinical, psychological, and biological variables at baseline and follow-up. Correlation analyses will explore relationships between predictors and primary and secondary outcomes.
Comparisons between subgroups
* Cluster analyses will be performed to identify subgroups of participants with different profiles of personality traits. These cluster will be compared regarding predictors, mediators/moderators, secondary outcomes, and primary outcomes.
* Between-group comparisons will also be conducted using t-tests, ANOVA or nonparametric alternatives (e.g., Mann-Whitney U tests) with regard to predictors and outcomes.
Longitudinal Regression Analyses
* Linear Mixed-Effects Models (LMM): These will evaluate changes in continuous outcomes over time.
* Generalized Estimating Equations (GEE): These models will analyze categorical outcomes, accounting for repeated measures and within-subject correlations.
* Logistic Regression: Logistic models will predict binary outcomes at follow-up.
Mediation and Moderation Analyses
* Mediation Analysis: mediation models will assess how variables mediate the relationship between predictors and primary and secondary outcomes.
* Moderation Analysis: Moderation models will explore how variables influence the relationship between predictors and primary and secondary outcomes.
Survival Analysis
- Cox proportional hazards models will be used to analyze time-to-event data, such as time to dropout and relapse.
Inflammatory Biomarker Analyses
- Levels of inflammatory markers in the ED samples will be compared to samples from individuals with other psychiatric disorders, as well as with healthy controls. Since blood samples will be taken upon repeated times during the study period, comparison of levels of inflammatory markers during disease course will be possible.
Missing data will be addressed as instructed for each instrument, ur by using multiple imputation or mixed-model approaches.
Subgroup Analyses
- Separate analyses will be conducted for adolescent and adult cohorts to examine potential differences in predictors and outcomes.
All statistical analyses will be performed using appropriate software (R, SPSS), and sensitivity analyses will be conducted to assess the robustness of findings.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 800
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Eating disorder examination interview (EDE-I) At baseline and at two-year follow up EDE-I is a semi-structured interview for assessing symptoms of and diagnosing eating disorders, including providing information for grading severity according to e.g., the DSM 5. The EDE-I assesses a variety of eating disorder behaviors, weight control behaviors, and behavioral and cognitive features of eating disorder psychopathology.
Eating disorder Examination Questionnaire (EDE-Q) At baseline, follow-up after treatment, and at 2, 5, 10, and 20 years follow-up. EDE-Q is a 28-item self-report questionnaire, designed to assess the range, frequency and severity of behaviors associated with an eating disorder. It is categorized into four sub-scales: Restraint, Eating Concern, Shape Concern and Weight Concern, and an overall global score. The score is obtained by calculating the mean for the total score and the subscales respectively (min = 0, max =6), higher scores indicate more severe eating disorder symptoms.
Eating Disorder-15 (ED-15) and for parents/caregivers (ED-15-P) ED-15 at baseline, follow-up after treatment, and at 2, 5, 10, and 20 years follow-up (youth cohort only). ED-15-P At baseline, follow-up after treatment, and at 2 years follow-up. ED-15 assesses eating disorder attitudes and behaviors on a 15-item Likert scale, which includes 10 attitudinal items (scored from 0-6) and 5 items for frequency grading. ED-15-P include the same items but is answered by the youths caregiver instead. The ED-15 includes two attitudinal subscales: Weight \& shape concerns and Eating concerns. The Overall attitudinal score is the mean of the scores on all ten items. Higher scores indicate more severe eating disorder symptoms.
Clinical Global Impression-Severity (CGI-S) At baseline and at 2 year follow-up (youth cohort only). Global clinical rating of symptom severity on an 8-grade Likert scale (scored between 0-7). The CGI offers a clinician-determined summary that incorporates all available information, including the patient's history, psychosocial context, symptoms, behavior, and the impact of these symptoms on their functional ability. A higher score indicates a more severe psychopathology.
Eating disorder diagnosis during follow-up in registers Registry data is retrieved at follow-up 5, 10 and 20 years Eating disorder diagnosis (AN, BN, BED, EDNOS, OSFED, UFED), collected from the National registries held by the National Board of Health and Welfare.
- Secondary Outcome Measures
Name Time Method Clinical Impairment Assessment questionnaire (CIA) At baseline, follow-up after treatment, and at 2, 5, 10, and 20 years follow-up. The CIA is a 16-item self-report measure of the severity of psychosocial impairment due to eating disorder features, Each item is rated on a four-point Likert scale ranging from 'Not at all' to 'A lot'. The minimun score is zero and the maximum score is 48, with higher scores indicating a more severe impairment.
WHO Disability Assessment Schedule (WHODAS 2.0) At baseline, follow-up after treatment, and at 2, 5, 10, and 20 years follow-up (adult cohort only). WHODAS 2.0 measure individual dysfunction in six domains of daily activities (cognition, mobility, self-care, relationships with people, life activities, and participation). It is measured on a five-point Likert scale ranging from no difficulty, to extreme difficulty. The score is calculated by dividing the total score with the number of items, resulting in a minimum score of zero and maximum score of 4. Higher scores indicate higher disability.
Uppsala scale of Functional Impairment in Daily life (UFID and UFID-P for parents) UFID: At baseline, follow-up after treatment, and at 2, 5, 10, and 20 years follow-up (youth cohort only). UFID-P: At baseline, follow-up after treatment, and at 2 year follow-up. The UFID is a Five-item, five-point Likert scale that measures functional impairment in daily life on a score between 1-5. UFID-P includes the same items but is answered by the caregiver instead. Higher scores indicate more functional impairment.
Children's Global Assessment Scale (CGAS) At baseline and at 2 year follow-up (youth cohort only). CGAS is a rating of general functioning for children and young people aged 4-16 years old. The clinician assesses a range of aspects of psychological and social functioning and gives the child or young person a single score between 1 and 100, based on their lowest level of functioning.
EQ-Visual Analogue Scale (EQ-VAS) At baseline, follow-up after treatment, and at 2, 5, 10, and 20 years follow-up. The EQ-VAS is a vertical visual analogue scale that takes values between 100 (best imaginable health) and 0 (worst imaginable health), on which patients provide a global assessment of their health.
Social safeness and pleasure scale (SSPS) At baseline, follow-up after treatment, and at 2, 5, 10, and 20 years follow-up. The SSPS is an 11-item self-rating instrument that assesses the extent to which people experience their world as safe, warm, and soothing, and how connected they feel to others. Participants indicate their answers on a five-point Likert scale, ranging from 1 (almost never) to 5 (almost all the time). Scores are added together to produce a total score in the range of 11-55, with higher scores representing higher perceived social safeness and connectedness to others.
SSPS at baseline is a predictor/mediator/moderator, SSPS at follow-up is a secondary outcome.Loneliness scale At baseline, follow-up after treatment, and at 2, 5, 10, and 20 years follow-up. The Loneliness scale is an 11-item self-rating instrument includes a 6-item emotional subscale and a 5-item social subscale. Respondents are presented with a series of statements and asked to indicate the extent to which the statement applies to their situation on a four-point Likert scale. The total score can range between 0-11 with higher scores indicating greater feelings of loneliness.
The Loneliness scale at baseline is a predictor/mediator/moderator, The Loneliness scale at follow-up is a secondary outcome.UCLA Loneliness Scale At baseline, follow-up after treatment, and at 2, 5, 10, and 20 years follow-up. UCLA Loneliness scale is a self-rating scale designed to measure ones subjective feelings of loneliness as well as feelings of social isolation. The scale comprises three questions that measure three dimensions of loneliness: relational connectedness, social connectedness and self-perceived isolation. Participants indicate their answers on a four-point Likert scale, providing a total score between 4-16, with higher scores indicating greater feelings of loneliness.
The UCLA at baseline is a predictor/mediator/moderator, The UCLA at follow-up is a secondary outcome.Montgomery Åsberg Depression Scale Self-assessment (MADRS-S) At baseline, follow-up after treatment, and at 2, 5, 10, and 20 years follow-up. MADRS-S is a 9-item widely used self-rating measure of depressive severity. The intention of the scale is to give an image of the patients current state of mind. The patient grades how he/she felt during the last three days. Items are rated on a seven-point Likert scale, providing a total score between 0-54, with higher scores reflecting greater depression severity.
The MADRS-S at baseline is a predictor/mediator/moderator, The MADRS-S at follow-up is a secondary outcome.Comorbidity At baseline, after treatment, and at 2 year follow-up (from medical journals) and at 10 and 20 years follow-up (from national health registers).. Comorbidity (including e.g., mood disorders, anxiety disorders, substance use disorders, and psychotic disorders) will be assess from medical journals, where diagnoses are based om the semi-structured interviews Electronic Psychiatric Screening Interview for children (EPSI-C), The Mini-International Neuropsychiatric Interview (M.I.N.I) for DSM-5 or the Structured Clinical Interview for DSM-5 Axis I Disorders - Clinical Version (SCID-I CV). Comorbidity will also be assessed from national health registers.
Comorbidity at baseline is a predictor/mediator/moderator, comorbidity at follow-up is a secondary outcome.Descriptive information about psychosocial functioning Registry data is retrieved at follow-up 5, 10 and 20 years Number of children
Physical status - BMI At baseline, weekly during treatment, follow-up after treatment, and at 2 year follow-up. Self-rated att 5, 10, and 20 year follow-up. Weight and height will be combined to report BMI in kg/m\^2, assessed with a valid and reliable device in a standardized procedure.
BMI at baseline is a predictor/mediator/moderator, BMI at follow-up is a secondary outcome.Physical status - pulse At baseline, and at 2 year follow-up. The number of times the heart beats within a certain time period. Pulse at baseline is a predictor/mediator/moderator, Pulse at follow-up is a secondary outcome.
Physical status - blood pressure At baseline, and at 2 year follow-up. Blood pressure at baseline is a predictor/mediator/moderator, blood pressure at follow-up is a secondary outcome.
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Trial Locations
- Locations (1)
Uppsala University Hospital
🇸🇪Uppsala, Sweden