Psychological and biological mechanisms of cytokine induced depression

Depression is frequently seen in patients with medical illnesses yet the link between medical illnesses and depression remains unclear. There is increasing data to suggest that the array of depressive symptoms experienced by the medically-ill may involve inflammation. The activation of the immune system and the subsequent release of innate immune products such as cytokines can have important effects on behaviour. The treatment of choice for chronic viral hepatitis C, interferon-alpha IFN-alpha, acutely induces the production and release of other innate immune cytokines, and has been indicated to cause clinically significant depression in 30% of patients receiving treatment. This in turn can impair quality of life and affect treatment compliance. We and others use IFN-alpha induced depression as a model to identify alterations in psychological and biological pathways that predispose to depression in the medically-ill, and thus provide an explanatory link between inflammation and the subsequent behavioural changes. In this editorial, we aim to describe the main biological pathways involved in IFN-induced depression and to discuss psychological, clinical and biological factors that have been found to predict those who will develop more severe psychiatric symptoms during treatment with IFN-alpha. Among these, particular attention would be given to psychological traits, genetic polymorphisms regulating inflammation and serotonergic function, and changes in plasma levels of pro-inflammatory cytokines.