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Inflammation is a well-known risk factor for chronic physical illnesses. Evidence is building that inflammation is also a risk for mental illnesses making inflammation a common, modifiable mechanism which could potentially explain why mental and physical illnesses are highly comorbid.A rapid synthesis on factors associated to inflammation in the depressed chronically ill has been conducted. It led to the production of a theoretical model of the interplay between inflammation, depression, and chronic physical illnessFive categories of factors which mediate the association between chronic physical and mental illnesses have been isolated: 1- social-demographic factors, 2- social-economic background, 3- Adverse health behaviours, 4- psychological stress, 5- genetics. We also considered factors that moderate the association between physical and mental illnesses: psychological therapies and medications. A discussion on the influence of each factor on the interplay between inflammation, depression and chronic illness is then conducted to support advances in clinical and research practice, as well as training and education.

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