An investigation of factors affecting eating psychopathology and behaviour

Abstract

Background: Eating-related psychopathology may include restrained, disinhibited, or emotional eating as well as weight, shape, and eating concerns. There are many risk factors associated with disordered eating and eating disorders including environmental, genetic, metabolic, psychological and pharmacological factors. Understanding the influence of these factors on disordered eating behaviours of individuals with mental health disorders and the changes in eating behaviour under pharmacological treatment may provide insights into the underpinning mechanisms. This understanding might lead to novel ideas for treatment targets. Objectives: The aim of this thesis is to explore the genetic, biological and pharmacological factors associated with eating-related psychopathology and their potential therapeutic implications using various methodological approaches: 1. A systematic review and meta-analysis examining the effect of second-generation antipsychotics (SGAs) on eating-related psychopathology and behaviour. 2. A study using a twin-based model fitting and co-twin control design to investigate the relationship between depression and eating-related psychopathology. 3. A cross-sectional study of the biological markers leptin, insulin-like growth factor-1 (IGF- 1), insulin and insulin receptor substrate (IRS-1) and their association with demographic and clinical features of anorexia nervosa (AN). 4. A narrative review on the pharmacological treatment of eating disorders Results: In study 1, we found that hunger was increased in participants treated with SGAs with increased cravings for fat and carbohydrates and a small increase in dietary disinhibition and restrained eating. In study 2, we found that the variabilities in uncontrolled eating, emotional eating and cognitive restraints were moderately explained by genetic and non-shared environmental factors. This data also revealed higher covariation in monozygotic compared to dizygotic twins in uncontrolled eating, emotional eating and cognitive restraint. A moderate relationship was observed between lifetime depression and uncontrolled eating, emotional eating and cognitive restraint. After removing antidepressant users, the relationship between eating and depression was attenuated. In study 3, there were significant differences in leptin between those with acute AN (large effect) and recovered AN (recAN) (small effect) with healthy controls (HCs), and lower serum IGF-1 in people with acute AN compared to HCs (moderate effect). Leptin levels correlated with eating-related psychopathology (mainly eating concerns) in the AN and recAN groups combined. IGF-1 levels correlated with a history of depression diagnosis in the acute and recovered phases of AN. In study 4, a literature review revealed a potential benefit of the SGA olanzapine for people with AN in terms of weight gain and the effectiveness of the antidepressant fluoxetine in bulimia nervosa (BN). Discussion: Weight change and metabolic disturbances during treatment with SGAs might be a consequence of increased appetite, craving for sweet and fatty foods and disinhibited eating. Our twin study suggests a hereditary component to eating behaviours. The association between depression diagnosis and uncontrolled eating, emotional eating and cognitive restraint could be partly explained by antidepressant use, genetic and environmental vulnerabilities. In the cross-sectional study, leptin and IGF-1 were lower in individuals with AN compared to HC. Low leptin levels were associated with a low body mass index (BMI) and low levels of body fat. IGF-1 was positively correlated with depression diagnosis, which may indicate its role as a marker for cognition and mood regulation for depressive disorders. Conclusion: Overall, the findings of this thesis indicate that eating-related psychopathology and disordered eating behaviours may be a result of genetic and non-shared environmental factors such as treatment with SGAs. The SGA olanzapine might help with weight gain in people with AN. The new findings of this PhD thesis are the meta-analytic evidence for changes in appetite and eating behaviour during SGA treatment; the interaction of depression and the use of antidepressants on uncontrolled eating, emotional eating and cognitive restraint; and the high serum IGF-1 in AN with comorbid depression.