Study protocol of comprehensive risk evaluation for anorexia nervosa in twins (CREAT): a study of discordant monozygotic twins with anorexia nervosa

Maria Seidel,Ricard Nergårdh,Christopher Hübel,Magnus Sjögren,Jamie D Feusner,Lauren Breithaupt,Martin Schaefer,Ilka Boehm,Johan Zvrskovec,Annelie Billger,Katharina Collin Hasselbalch,Stefan Ehrlich,Ata Ghaderi,Virpi Leppä,Bengt T Fundin,Jessica Pege,Afrouz Abbaspour,Elisabeth Welch,Androula Savva,Camilla Wiklund,Emilie Vangsgaard Rosager,Laura M Thornton,Cynthia M Bulik

doi:10.1186/s12888-020-02903-7

Abstract

BackgroundAnorexia nervosa (AN) is a severe disorder, for which genetic evidence suggests psychiatric as well as metabolic origins. AN has high somatic and psychiatric comorbidities, broad impact on quality of life, and elevated mortality. Risk factor studies of AN have focused on differences between acutely ill and recovered individuals. Such comparisons often yield ambiguous conclusions, as alterations could reflect different effects depending on the comparison. Whereas differences found in acutely ill patients could reflect state effects that are due to acute starvation or acute disease-specific factors, they could also reflect underlying traits. Observations in recovered individuals could reflect either an underlying trait or a “scar” due to lasting effects of sustained undernutrition and illness. The co-twin control design (i.e., monozygotic [MZ] twins who are discordant for AN and MZ concordant control twin pairs) affords at least partial disambiguation of these effects.MethodsComprehensive Risk Evaluation for Anorexia nervosa in Twins (CREAT) will be the largest and most comprehensive investigation of twins who are discordant for AN to date. CREAT utilizes a co-twin control design that includes endocrinological, neurocognitive, neuroimaging, genomic, and multi-omic approaches coupled with an experimental component that explores the impact of an overnight fast on most measured parameters.DiscussionThe multimodal longitudinal twin assessment of the CREAT study will help to disambiguate state, trait, and “scar” effects, and thereby enable a deeper understanding of the contribution of genetics, epigenetics, cognitive functions, brain structure and function, metabolism, endocrinology, microbiology, and immunology to the etiology and maintenance of AN.

Highlights

Anorexia nervosa (AN) is a severe disorder, for which genetic evidence suggests psychiatric as well as metabolic origins
Adequate sample sizes are only attainable in locations with extensive twin registries, such as Sweden or Denmark
The study is demanding for participants and we have implemented a number of measures to ensure comfort and to express our deep appreciation of all participants

Summary

Methods

Basic characteristics and diagnosis Participants We are recruiting female MZ twins rigorously discordant for AN and healthy non-dieting age- matched female concordant unaffected MZ twin controls. In addition to the saliva kits for the monozygosity screening, participants are provided with a link to a validated diagnostic online questionnaire, ED100K [113] which captures lifetime DSM-5 eating disorder diagnoses This is a second stage of verifying that affected twins did have AN and that co-twins and control twins are unaffected. While pairwise comparisons seem the right approach if subgroups constitute of equal (high) number of study participants, one has to take into consideration that it might not be possible to clearly separate the group of affected twins into ill and recovered In this case we propose a working model of using recovery status as continuous variable that can be controlled for as covariate in subsequent analyses.

Discussion

Background

Findings