- Title
- Tyrosine as an adjunct treatment in anorexia nervosa: a noradrenergic repletion hypothesis
- Creator
- Hart, Melissa
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2014
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- Background: Anorexia nervosa (AN) is a severe and complex illness with high mortality, lack of clear aetiology or efficacious treatments and very few published clinical trials to guide effective treatment. There is a pressing need for the development of interventions that could potentially modify causal factors in AN. One line of research proposes that noradrenergic dysregulation may be a major factor in the causation of AN. This doctoral thesis extends the noradrenergic dysregulation hypothesis by proposing a substrate-repletion intervention hypothesis. Methods: Several studies were conducted as part of this thesis. First, the extent of AN in (the State of) New South Wales (NSW (Australia), where the studies in this thesis were conducted, is relatively unknown. A secondary analysis of existing NSW Ministry of Health hospital inpatient data was conducted to explore admissions for children and adolescents with an eating disorder over a ten year period (Statewide Data Analysis). Secondly, as the literature on tyrosine administration in people with AN or healthy peers is sparse, pharmacokinetic studies were conducted on two adolescents with AN and two healthy peers (Solubility and Metabolism Studies). Finally, in order to test the hypothesis that adolescents with AN require a constant supply of tyrosine, a randomised controlled trial (RCT) was planned (Tyrosine Study). The original aim of the RCT was to assess the effectiveness and acceptability of tyrosine supplementation, however, due to recruitment difficulties this was conducted as a feasibility study. The trial involved ongoing administration of tyrosine over a 12 week period (in addition to treatment as usual) to explore the effects of tyrosine administration on eating disorder and more general psychopathology in adolescents with AN. Factors influencing study feasibility, including RCT participation (recruitment and retention) and supplement compliance were investigated (Acceptability Study). Results: Analysis of inpatient data indicated that moderate-to-severe eating disorders in NSW are a significant public health problem (annual hospital admission rate of 82 per 100,000 for 5-18 year olds) and the frequency of admissions did not decline over time (2000-2010). The pharmacokinetic studies showed that the encapsulated tyrosine produced a notable increase in plasma/blood tyrosine, suggesting sufficient solubility and absorption. Results of the RCT feasibility study suggest greater improvements in Weight and Shape Concern (RCI= -2.29 to -2.93), the eating disorders Global Score (RCI= -2.89) and executive and frontal functioning in the tyrosine group. Recruitment for the RCT proved problematic (n=7). Several factors influencing recruitment were identified. Conclusion: This thesis offers a unique and in-depth exploration of a substrate-repletion intervention in AN. Although firm conclusions could not be drawn, preliminary results are consistent with the proposed hypothesis and importantly highlight a range of key factors that require consideration for further research. These include developing a comprehensive recruitment and retention plan, concentrating recruitment efforts in large, established specialist programs, broadening study inclusion criteria, refining the written and verbal presentation to participants, and conducting dosage, safety, compliance and acceptability studies.
- Subject
- anorexia nervosa; tyrosine; noradrenaline
- Identifier
- http://hdl.handle.net/1959.13/1055866
- Identifier
- uon:15950
- Rights
- Copyright 2014 Melissa Hart
- Language
- eng
- Full Text
- Hits: 783
- Visitors: 1094
- Downloads: 331
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT01 | Abstract | 133 KB | Adobe Acrobat PDF | View Details Download | ||
| View Details Download | ATTACHMENT02 | Thesis | 2 MB | Adobe Acrobat PDF | View Details Download |