Chronic stress, neuroinflammation, and depression: an overview of pathophysiological mechanisms and emerging anti-inflammatories

In a subset of patients, chronic exposure to stress is an etiological risk factor for neuroinflammation and depression. Neuroinflammation affects up to 27% of patients with MDD and is associated with a more severe, chronic, and treatment-resistant trajectory. Inflammation is not unique to depression and has transdiagnostic effects suggesting a shared etiological risk factor underlying psychopathologies and metabolic disorders. Research supports an association but not necessarily a causation with depression. Putative mechanisms link chronic stress to dysregulation of the HPA axis and immune cell glucocorticoid resistance resulting in hyperactivation of the peripheral immune system. The chronic extracellular…