Title: Depression in paediatric chronic fatigue syndrome (CFS/ME)
Funder: Department of Health and Social Care

Abstract: Background: Chronic fatigue syndrome (CFS), or myalgic encephalomyelitis (ME) is characterised by persistent, disabling fatigue in the absence of an underlying cause. It is relatively common (1 - 2.4%) and disabling. Approximately 30% of adolescents with CFS/ME probably have depression. Those with probable co-morbid depression are more disabled, have worse fatigue and more pain than those without depression. Despite this, we know remarkably little about co-morbid depression in paediatric CFS/ME. We do not know whether depression in paediatric CFS/ME changes treatment outcome as it may do in adult CFS/ME. Epidemiological studies, clinical services and treatment trials in CFS/ME have only used questionnaires (for example, the Hospital Anxiety and Depression Scale, HADS) and not the gold standard structured diagnostic interview to identify those with depression. We are therefore not certain what the prevalence of DSM-IV defined co-morbid clinical depression is in paediatric CFS/ME, whether particular groups of adolescents are at higher risk of developing depression and how depression affects prognosis. Aim: To improve the recognition and treatment of adolescents with CFS/ME and co-morbid depression. Question to be addressed: What is the best way to identify and treat paediatric CFS/ME and co-morbid depression? Plan of Investigation: Study 1. I will establish the prevalence of co-morbid depression in a clinical cohort (N=323, age 11-18 with diagnosis of CFS/ME) using a structured diagnostic interview (Kiddie Schedule for Affective Disorders and Schizophrenia, KSADS). I will use Receiver Operating Characteristic (ROC) curves to quantify diagnostic accuracy and investigate the sensitivity and specificity and determine the optimum threshold for both the HADS and the Revised Child Anxiety and Depression Scale (RCADS). Study 2. I will perform the following secondary data analysis from 6 month follow-up data from study 1, the RECOVERY study (a prospective cohort study, N=214) and the MAGENTA trial (a RCT comparing behavioural treatments for CFS/ME, N = 28 as of January, 2016, anticipated 220 by February, 2018). 1. Identify the characteristics associated with co-morbid depression at baseline using logistic regression. 2. Investigate whether depression affects prognosis by comparing physical function (SF-36 physical function subscale) at 6 months between those who are and are not depressed using multivariable linear regression adjusting for baseline SF36-PFS, and variables shown to be associated with depression. Additional analyses will adjust for allocated treatment in the trial. Sensitivity analyses will exclude adolescents who received CBT in the prospective cohorts. Study 3: I will add two further questionnaires (Children's Negative Cognitive Errors Questionnaire Revised; Cognitive and Behavioural Responses to Symptoms Questionnaire) to the FITNET-NHS trial comparing internet delivered therapies for CFS/ME (CBT versus activity management, N = 734) to investigate whether there is a difference in negative cognitive errors and cognitive and behavioural responses to CFS/ME in adolescents with and without co-morbid depression. Study 4 I will run two expert groups (15-20 multidisciplinary clinicians) and two patient advisory groups to support the development of a theoretical model of factors contributing to depression in adolescents with CFS/ME using the findings of studies 2 and 3. This will inform the development of a new treatment approach for paediatric CFS/ME with co-morbid depression. Benefits to patients and the NHS: NHS commissioners and service providers will benefit from knowing the actual prevalence of co-morbid depression in paediatric CFS/ME. Clinicians and those conducting treatment trials will benefit from knowing how best to screen for depression, and what thresholds to use on the screening tools. Clinicians will improve the targeting of treatment as they will know the characteristics of adolescents at risk of depression. Developing improved treatment will benefit patients, their families and NHS providers.

Lay abstract: Chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME) affects approximately 1 - 2 teenagers in every 100. It interferes significantly with their day-to-day lives. For example, on average, children and young people with CFS/ME miss one year of school. We think that about 1 in 3 children and young people with CFS/ME also have depression. Those with depression seem to be more disabled, experience more pain, and don't seem to recover as well from CFS/ME. Aim My research aims to improve the recognition and treatment of teenagers who have both CFS/ME and depression. It will result in us knowing how to identify depression, who is most at risk of getting depression, and a new treatment approach specifically tailored to help this group of patients to recover.Plan This research will: 1)Find out how many teenagers with CFS/ME actually have depression and how best to identify them. I will recruit teenagers with CFS/ME after their first appointment with the specialist paediatric CFS/ME service in Bath. Teenagers with CFS/ME will be interviewed to assess depression, and asked them to fill in two short questionnaires about symptoms of depression. They can choose to be interviewed by Skype or face-to-face, at home or at the hospital. I will analyse how good the questionnaires are at picking up depression in these patients so that we know which questionnaire is best to use. 2)Existing data will be analysed for patterns to see whether particular groups of teenagers with CFS/ME (e.g. boys or girls, older or younger teens) are more likely to have depression than others and to see what impact having depression has on recovery with different treatments (after 6 months). 3)Explore whether there are differences in how teenagers with CFS/ME with depression think, compared to those without depression. Teenagers in the FITNET-NHS trial, which is testing internet-delivered treatments for CFS/ME, will be asked to fill in two short questionnaires online before they start treatment. One questionnaire looks at the way people think in response to common situations, and the other looks at how they think about their CFS/ME symptoms. This research will help us to discover: how much of a problem depression is, how to spot depression who is most at risk of depression more about how depression affects recovery from CFS/ME, the particular thinking patterns we should help these teenagers with. The information gained from this research will be used to develop a treatment approach specifically for teenagers with CFS/ME and depression. The treatment approach will be developed by a group of people with relevant experience and will include a group of between 6 and 12 patients (teenagers with CFS/ME) and parents of teenagers with CFS/ME who I will meet with twice. Sharing this information Throughout this project, I will work closely with the Association of Young People with ME (AYME) to share the findings with children, young people and families affected by CFS/ME by various means; e.g. social media, AYME website. The research findings will be written up in an accessible format and shared widely with professionals and patients as the project progresses. In addition, articles will be published in journals that are read by other people working with children and young people who have CFS/ME and findings will also be shared at conferences. At the end of the project, I will travel across England to visit all the specialist teams who work with children and young people with CFS/ME to train their psychologists in using the new treatment approach that has been developed for teenagers with CFS/ME and depression.

Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL;4.4 POPULATION SCREENING
Health categories: MENTAL HEALTH;DISPUTED AETIOLOGY AND OTHER