Psychosocial stress and systemic disease can both affect the onset of depression. For example, the comorbidity of depression in patients with diabetes, cancer, or cardiac disease is 17%–29%, much higher than that of the general population (10.3%) (% comorbidity of depression with specific systemic illnesses is shown in Table 1) (Evans et al., 2005). Moreover, chronic inflammation is implicated in the pathology of these diseases, and the possible mechanisms by which the NLRP3 inflammasome may serve as a key mediator is being elucidated (Table 1). There is also evidence from clinical procedures that inflammation can cause depression. For example, interferon (IFN) a cytokine that strongly activates the immune system (e.g., natural killer cells and macrophages), is used as a treatment for certain types of cancer and viral infections and causes a high prevalence of dose-dependent depressive symptoms (~50%) (Raison et al., 2006). Immune reactivity and inflammation has thus been implicated as a common factor underlying depressive effects of IFN.
