The Triple A study (Adolescents with Anorexia and Autism): A search for biomarkers

Lead Research Organisation: King's College London
Department Name: Psychological Medicine

Abstract

Anorexia Nervosa (AN) is a complex eating disorder, associated with a high physical and psychological risks, it has the highest death rate amongst psychiatric disorders. Treatment resistance is a huge challenge for clinicians and researchers, as approximately 50% of individuals diagnosed with AN do not respond to treatment and go on to develop a more severe and chronic form of the disorder. Research exploring thinking styles and the emotional profile of individuals with AN have demonstrated differences in thinking processes between those with AN and those who have never had an eating disorder. These include tendencies towards an inflexible thinking style, becoming stuck in details and difficulty with social functions such as recognising and expressing emotions and interacting with others. Brain imaging studies have also highlighted different patterns of brain function during these processes in individuals with AN. These difficulties are suggested to be a major contributing factor to the development and maintenance of the disorder.
These characteristics are also defining symptoms of Autism Spectrum Disorder (ASD), which has led to research focussing on the overlap between AN and ASD. Although ASD and AN are associated with opposite gender ratios (ASD being more common in males, AN more common in females), recent findings demonstrate that a proportion of adult females with severe and chronic AN have elevated levels of autistic symptoms. Such elevated ASD traits are also associated with poorer treatment outcomes.
There is little work focussing on this illness profile at the early stages of the disorder, and research is urgently need to examine both the cognitive and neurobiological profile of young people with AN when they first present with the disorder, also considering the potential role of ASD symptoms in their recovery.
Research examining brain activity during thinking and emotional processing has largely been conducted within an adult AN population, and further research is required to explore if there are similar abnormalities and differences in the brain activation of young people with AN, and how this may change as the illness progresses or when weight is restored. Exploring the impact on the brain at first presentation, during the illness and after recovery in young people will help define risk and maintaining factors and help predict treatment outcome. Overall, this work is likely to help develop treatment targeted at early illness stages, disrupt illness progression and reduce the percentage of individual going on to develop a more severe and enduring form of the disorder.
This study is the first of its kind to integrate innovative neuroimaging methods, neuro-cognitive measures and to develop profiles of the brain of adolescent AN patients with combined ASD symptoms when they are first presenting for treatment. This will allow for the study of the interaction between clinical features, thinking and social functioning styles. At baseline assessment adolescent patients with AN, those that have recovered from the disorder and age-matched healthy individuals will be asked to complete clinical and neuropsychological assessments, an MRI scan and questionnaires. Participants with current AN and recovered AN will then be asked to repeat these measures six months later (following treatment) to identify any differences in that may help predict treatment response or relapse.
We will use this data to build a database of critical factors influencing AN, including cognitive, emotional, brain imaging markers. This research and future larger scale investigations based on this study will help identify the most vulnerable patients at an earlier stage and those individuals unlikely to respond to current interventions. These findings may then be applied to create a more individualised support and treatment strategies.

Technical Summary

Current research suggests that cognitive and emotion processing difficulties along with autistic symptoms contribute to the maintenance and development of anorexia nervosa (AN). However, these findings are based on work conducted largely in adults with AN and despite the fact that the illness typically develops during adolescence and that illness duration is likely to moderate treatment resistance in AN due to the presence of neuroprogressive changes. Thus, further work is needed to document the neurocognitive profile of AN during the early stage of their illness.
The proposed study aims to investigate neurobiological factors that may contribute to the development and maintenance of AN in children and adolescents first presenting for treatment using behavioural assessments and functional magnetic resonance imaging (fMRI). To achieve this aim we will investigate differences in the neural correlates of cognitive and emotional processing between three groups of young people aged 12-18 years, namely 40 patients with AN, 20 young people who have recovered from AN (recAN), and 40 age matched healthy controls (HC). Specifically, we will investigate differences in BOLD signal change during central coherence and emotional processing tasks using a 3T fMRI scanner. We will also explore correlates between resting state BOLD signal and performance on cognitive tasks assessing central coherence and cognitive flexibility conducted outside of the scanner. We will then examine how these differences in BOLD signal change correlate with presence of ASD symptoms as measured during a diagnostic interview in the AN and recAN groups. Finally, we will use supervised machine learning techniques to investigate BOLD signal patterns that predict the state of psychopathology as measured with a battery of self-report questionnaires and interviews at 6-month follow-up in the AN and recAN groups.

Planned Impact

Anorexia nervosa (AN) has devastating consequences including not only on the individual due to lasting effects of starvation on the brain leading to treatment resistance, and ultimately death, but also on families' and carers' wellbeing. AN also has substantial financial impact on societal level costing UK economy approximately £1.25 billion per annum. Current research suggests that treatments should target the cognitive and emotion processing difficulties along with autistic symptoms that contribute to the maintenance and development of AN. However, because these findings are based on work conducted largely in adults with AN, there is pressing need for better understanding of the aetiology of AN during the early stages of illness to improve treatment outcome and reduce the devastating impact of the illness. We propose that improved understanding of the impact of autistic symptoms and the neural mechanisms that underlie difficulties in cognitive and emotional processes during early stages of illness has many practical implications.
Better understanding of the underlying neural mechanisms of AN during the early stages of illness, would allow for the development of new neurobiological models of AN that shifts focus from solely external influences, such as social and family, to include internal influences that integrate genetic and neurobiological contributions, across the age span. These findings and models would highlight the neurobiological bases of the illness, which can help lift some of the shame and stigma associated with the diagnosis. Stigma and shame have negative impact on agency in help-seeking, which further contribute to long duration of illness and treatment resistance due to denial.
Identification of neural inefficiencies present in young people with AN, allows for better understanding of the illness-related underlying mechanisms that contribute to the development of AN as well as the neuroprogressive changes that occur as a consequence of the illnes. These findings could improve understanding of what mechanisms behavioural or non-invasive neurobiological treatments (e.g. TMS) should be targeting during the early stages of illness. The tasks used also easily lend themselves to a test battery that could be used to examine the effectiveness of new or currently available treatments. The findings can also shed light on the mechanisms through which the treatments work to allow further understanding of their effectiveness and their further improvement.
Finally, the findings from the study will also shed light on early diagnostic and neurobiological markers present at admission that predict good or poor response to currently available eating disorder treatments. These findings allow identification of predictors of potential chronicity early on and identify differences between treatment responders and non-responders. Treatments could then be developed to specifically target the non-responders who do not benefit from currently available treatments.
Therefore, the findings from the proposed study have substantial practical clinical implications and will help further understanding of the aetiology of AN as well as make contributions to evidence based medicine to target chronicity and treatment resistance.

Publications

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Adamson J (2018) Effectiveness of emotional skills training for patients with anorexia nervosa with autistic symptoms in group and individual format. in European eating disorders review : the journal of the Eating Disorders Association

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Dandil Y (2020) Individual cognitive remediation therapy benefits for patients with anorexia nervosa and high autistic features. in European eating disorders review : the journal of the Eating Disorders Association

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Emma Kinnaird (2019) Same behaviours, different reasons in International Review of Psychiatry

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Kerr-Gaffney J (2018) Eye-tracking research in eating disorders: A systematic review. in The International journal of eating disorders

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Kinnaird E (2019) Investigating alexithymia in autism: A systematic review and meta-analysis. in European psychiatry : the journal of the Association of European Psychiatrists

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Kinnaird E (2018) Taste sensitivity in anorexia nervosa: A systematic review. in The International journal of eating disorders

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Kinnaird E (2019) Same behaviours, different reasons: what do patients with co-occurring anorexia and autism want from treatment? in International review of psychiatry (Abingdon, England)

 
Description Advising the Department of Health and NHS England with short briefings to provide a snapshot of the current evidence of ASD and AN link
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
Description Comorbidity Anorexia Nervosa and Autism Spectrum disorders in women
Geographic Reach National 
Policy Influence Type Influenced training of practitioners or researchers
 
Description The Health Foundation innovation award
Amount £75,000 (GBP)
Funding ID 1115447 
Organisation The Health Foundation 
Sector Charity/Non Profit
Country Denmark
Start 03/2019 
End 04/2020
 
Title New analytical algorithm for MRI data 
Description We are in the process of developing a new non-linear method to model the brain responses to a ventrilated stimuli in MRI - a flexible model using the inverse logit function to allow for fluctuations in both onset and duration of signal. 
Type Of Material Computer model/algorithm 
Year Produced 2018 
Provided To Others? No  
Impact It will be of interest to the broader neuroimaging community once finalised and tested - it will help to reduce bias, mis-modelling, and power loss. 
 
Description Online study expanding upon themes of the MRC Award 
Organisation Swiss Anorexia Nervosa Foundation
Country Global 
Sector Charity/Non Profit 
PI Contribution Problematic Eating on the Autism Spectrum - an online study with ~1000 participants examining eating disorders and disordered eating among autistic and neurotypical individuals, beyond the scope of Anorexia Nervosa. Post-doc developed, designed, and ran study, and is currently conducting analyses and write up of publications.
Collaborator Contribution Some sponsorship of the study.
Impact We anticipate 7 peer-reviewed publications from the study. Two talks have been given at academic conferences based upon the data, and more are anticipated.
Start Year 2017
 
Description Adelaide University of South Australia Department of Psychology 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I received Norman Munn Distinguished Visiting Scholar Award to spend 6 weeks sabbatical in Adelaide University of South Australia, Department of Psychology.
I have presented lecture on my research portfolio and ne day workshop. Attendees in both of this events were professionals working in experimental and clinical psychology.
several new collaborations will start as a result of this visit.
Year(s) Of Engagement Activity 2018
 
Description Clinician CPD Session 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Post-doc from project delivered CPD to a group of approx 15 clinicians, training them in autism and mental health overlap in females. This resulted in disucssions of potential treatment adaptations within the service.
Year(s) Of Engagement Activity 2018
 
Description Denmark Summer School in mental health 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Summer schools in Denmark have one or two international speakers to share best practice experience.
Workshop was delivered about our clinical work with challenging patients who have comorbid conditions.
Year(s) Of Engagement Activity 2018
 
Description Lecture to Masters Students 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact Post-doc gave a lecture on autism and mental health in females to a Masters course, with dicussions of implications for both theory and practice in mental health services and scholarship, including expanding student knowledge about autism in females.
Year(s) Of Engagement Activity 2018
 
Description Talk to clinicians 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Post-doc gave talk to clinical services team about neuroimaging, it's use and uses, and applicability to their practice.
Year(s) Of Engagement Activity 2017
 
Description https://www.bbc.co.uk/programmes/p07234cj 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact It is bbc 2 Victoria Derbyshire's programme.
I gave interview and spoke about eating disorder and autism spectrum comorbidity.
Year(s) Of Engagement Activity 2019
URL https://www.bbc.co.uk/programmes/p07234cj
 
Description https://www.medicalresearchfoundation.org.uk/news/q-a-exploring-the-interplay-between-anorexia-and-autism 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Q and A with Senior Communications Manager Medical Research Foundation about the project.
Year(s) Of Engagement Activity 2019
URL https://twitter.com/MedResFdn/status/1100002004942970882