Authors: F Van den Eynde, S Helder, J Day, L Sternheim, H Davies, K Tchanturia, I Campbell, J Treasure, D Collier, U Schmidt
Centre: Section of Eating Disorders, Institute of Psychiatry, King's College London, De Crespigny Park, London, SE5 8AF, United Kingdom

Background

Anorexia Nervosa (AN) is a life-threatening illness that runs a chronic, relapsing course and is associated with high mortality rates (Berkman et al 2007). There is evidence that the course of the illness has become more severe over the last decades. The response to treatment remains poor with only about 30% of AN patients in remission after one year of specialist treatment. Importantly, little is known about the actual symptom progression over time and associated clinical and physiological changes that occur during treatment. Longitudinal research is essential to establish and explain the psychopathological and pathophysiological ‘events' that occur in the course of the illness. However, data are very scarce. In a pilot study (duration 2 weeks) using an ecologic momentary assessment strategy, food restriction behaviour, stressful events and mood lability were found to be intercorrelated (Engels et al 2005). An influential methodological approach is the moderator - mediator concept (Kraemer et al 2001). In essence, a moderator suggests on whom or under what conditions a treatment produces its effect, whereas a mediator suggests how and why (Baron and Kenny 1986, Kraemer et al 2001). Moderators or risk factors in AN have been extensively investigated. In contrast, mediator research in eating disorders is in its infancy. Key components in the clinical presentation of AN are anxiety-related processes, stress responsiveness and physical hyperactivity. Anxiety is arguably the most common comorbid psychopathology: it often predates the onset of the illness (Raney et al 2008) and negatively influences outcome (e.g. Herpertz-Dahlmann et al1996). Intolerance of uncertainty and worry are important process components in anxiety disorders and therefore may be important in AN (Simmons et al. 2008). There is evidence that stress responsiveness is increased in AN and an aberrant HPA axis response to chronic stress has been proposed to be a maintaining factor (Connan et al 2007). Finally, elevated physical activity (hyperactivity) is a worrisome symptom that leads to accelerated weight loss and also often leads to treatment discontinuation (Casper 1998). Data on the relationship between activity levels and outcome in AN are scarce. In a longitudinal study, Van Elburg et al (2007) were unable to show a strong relationship between physical activity levels and the course of recovery although other groups have reported that weight restoration is associated with a decrease in hyperactivity (Holtkamp et al 2006, Hebebrand et al 2003). In summary, it is unclear whether these clinically highly relevant factors are mediators of the treatment process in AN.

Aims

The aim of this research is to investigate whether the intermediate factors anxiety-related processes, stress responsiveness and levels of physical activity are mediators of treatment response in AN.The objective is to conduct a longitudinal naturalistic study to demonstrate correlations between changes in these intermediate factors and changes in eating disorder related outcome measures.We hypothesise that changes in a) the level of intolerance of uncertainty and level of worry, b) stress-responsiveness and c) physical activity, will correlate with changes in eating disorder related outcome variables.

Methods and Materials

Forty female in-patients (aged between 16 and 65 years) with a DSM-IV diagnosis of AN (Restricting and Binge-Purging subtypes) will be recruited from the South London and Maudsley (SLAM) NHS Foundation Trust's services (London, UK) for this exploratory naturalistic study.Subjects will be assessed 4-weekly (week 4, 8 and 12) over a period of 3 months and a follow-up assessment will be completed at 24 weeks. The in-patient treatment at the Bethlem Royal Hospital (SLAM) comprises a variety of psychological interventions including cognitive behavioural therapy, motivational enhancement therapy and family work and is delivered by members of the multi-disciplinary team.Baseline assessments will include demographics and the Structured Clinical Interview for DSM (SCID-I) screening. Eating disorder related outcome measures, the Eating Disorder Examination-Questionnaire (EDE-Q) and WHO-QOL-BREF, will be completed at enrolment and at 12 and 24 weeks. BMI and the Short Evaluation of Eating Disorders (SEED) will be completed at enrolment and at weeks 4, 8, 12 and 24.Anxiety-related pathology will be assessed at enrolment and at weeks 4, 8, 12 and 24 with the Depression Anxiety Stress Scale, the Penn State Worry Questionnaire and the Intolerance Uncertainty Scale. At the same assessment points, stress-responsiveness will be assessed by measuring morning salivary cortisol levels, physical activity will be measured using wrist actigraphy. The latter device will be used on three consecutive days at each assessment point..

Statistical Analysis of the Data

For the mediation analyses, a three-step process as described by Baron & Kenny (1986) will be used. All analyses will be performed with linear or logistic regression. This will be performed in collaboration with the Statistics and Computing Department at the Institute of Psychiatry. 

Main Limitations and Potential Consequences

The study design does not allow to us determine causality. However, the results are expected to provide more insight in the processes that occur when people with AN are in treatment and how and why treatment is effective. In its turn, this might provide new treatment targets or alternatives for evaluating treatment progress.  

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