Neuroinflammatory theory of depression

Abstract

Major depressive disorder is becoming one of the most prevalent neuropsychiatric disorders. Although the etiology or neurobiological bases are unknown, several theories have been proposed such as the monoaminergic or neurotrophic theories. Preclinical and clinical studies showing interaction between inflammation and neural function in depression are becoming increasingly important, supporting the neuro-inflammatory theory. In this regard, depressive disorders have been shown to be related to hypothalamic-hypophysial-adrenal (HPA) hyperactivity (resulting in an elevated glucocorticoid levels) and also a hyperactive immune response. Elevated concentrations of inflammatory markers, such as pro-inflammatory cytokines, have been reported in the central and peripheral nervous systems of depressive patients. Additionally, peripheral cytokines are able to reach the brain and affect most pathophysiological pathways related to depression. These include neurotransmitter metabolism, neuroendocrine function, and neural plasticity or adaptation. Furthermore, brain inflammation is able to induce pathophysiological adaptations similar to those which occur during depression, including reduction of neurotrophic factors, steroidal toxicity and the resulting oxidative stress. Chronic damage caused by cytokines leads to long-term changes in brain anatomy and functioning, consequently affecting mood, cognition and/or behavior. In fact, results obtained in patients with inflammatory diseases suggest that reduced levels of proinflammatory cytokines could help to improve depressive symptoms and may even enhance the response to conventional antidepressant treatments. Therefore, the development of treatments targeting brain inflammation and immune response may be an pportunity to improve the symptomatology of depressed patients.