Depression, the Metabolic Syndrome and Neurodegeneration

Abstract

The review summarises the evidence that chronic low grade inflammation triggers a number of metabolic changes that are ultimately responsible for the physical ill-health (such as type 2 diabetes, heart disease and cancer) which frequently characterise major depression. The possible mechanisms involve a dysfunction of glucose metabolism due to an insensitivity of insulin receptor signalling which results from the action of superoxide radicals produced by intermediates of the tryptophan–kynurenine pathway. Additional metabolic changes occur as a result of a decrease in mitochondrial activity. Increasing epidemiological and clinical evidence suggests that chronic depression is often a prelude to dementia in later life. Possible metabolic mechanisms whereby this occurs involve the neurodegenerative effects of pro-inflammatory cytokines, the consequences of oxidative stress and the action of the neurotoxins formed by the tryptophan–kynurenine pathway. The review concludes with a summary of some of the nutritional factors that may have a neuroprotective action, largely due to their anti-inflammatory effects.