Adrian Lopresti

Major depression is associated with multiple dysregulated biological pathways which are influenced by an array of lifestyle, psychological, environmental and biological factors. Nutraceuticals including curcumin, derived from the Indian spice turmeric, also have the potential to influence these depressogenic pathways. Consequently, the aims of this thesis were to: 1. Review and integrate research on dysregulated biological pathways, namely those associated with neurotransmitter imbalances, immuno-inflammatory processes, hypothalamus-pituitary-adrenal axis dysregulation, oxidative and nitrosative stress, mitochondrial dysfunction and neuroprogression. 2. Review research on the relationship between several lifestyle-based factors and depression, and examine their effects on these depressogenic pathways. More specifically, the influence of diet, exercise, sleep, vitamin D, omega 3 essential fatty acid deficiency, stress and trauma, obesity and smoking were appraised along with their potential to prevent and treat major depression. The influence of psychological and pharmaceutical interventions on these dysregulated biological pathways was also reviewed. 3. Examine the antidepressant effects of curcumin. In animal-based models, curcumin has demonstrated antidepressant effects, although clinical studies are lacking. The efficacy of curcumin in an 8-week, randomised, double-blind, placebo-controlled study was examined in people with a major depressive disorder. Curcumin at a dose of 500 mg, twice daily, was compared with a placebo. The Inventory of Depressive Symptomatology-Self Report (IDS-SR30) and Spielberger State-Trait Anxiety Inventory were used to assess symptomatic change. Curcumin and placebo were equally effective in lowering depressive and anxiety symptomatology from baseline to week, but from weeks 4 to 8 curcumin supplementation was associated with superior antidepressant efficacy. 4. Review the potential role of peripheral biomarkers in major depression and examine biomarker changes following curcumin supplementation. Measurement of peripheral biomarkers has the potential to enhance diagnosis, evaluate treatment progress and facilitate treatment matching. In a randomised, double-blind, placebo controlled study, the influence of curcumin on several urinary, plasma and salivary peripheral biomarkers was examined. The efficacy of biomarkers to predict treatment efficacy from curcumin administration was also examined. Urinary leukotriene B4, thromboxane B2 and substance P were associated with changes following curcumin treatment, while higher baseline concentrations of plasma endothelin-1 and leptin were associated with greater treatment efficacy. Limitations associated with the clinical studies are reviewed and recommendations for future research are provided.