This chapter explores the evidence supporting inflammation-associated depression. Data to date suggest a bidirectional relationship between inflammation and depression wherein one process can drive the other. A wealth of animal and clinical studies have demonstrated an association between concentrations of pro-inflammatory cytokines - specifically interleukin (IL)-1β, IL-6, and tumor necrosis factor-α - and depressive symptoms. There is also evidence that this pro-inflammatory state is accompanied by aberrant inflammation-related processes including platelet activation factor hyperactivity, oxidative and nitrosative stress, and damage to mitochondria. These complex and interrelated mechanisms can collectively contribute to negative neurobiological outcomes that may, in part, underlie the etiopathology of depression. Mounting evidence has shown a concomitant reduction in both depressive symptoms and pro-inflammatory cytokine concentrations following treatment with pharmacological anti-inflammatory interventions. Taken together, the reviewed preclinical and clinical findings may suggest the existence of a distinct inflammatory subtype of depression in which these patients exhibit unique biochemical and clinical features and may potentially experience improved clinical outcomes with inflammation-targeted pharmacotherapy.
Keywords: Cell-mediated immune activation; Cytokines; Inflammation; Major depressive disorder; Mitochondrial dysfunction; Oxidative and nitrosative stress; Platelet activating factors.