Inflammatory Process and Immune System in Major Depressive Disorder

Abstract

Major depressive disorder (MDD) is one of the most common psychiatric illnesses in the general population. In mental disorders, the activation of inflammatory pathways in the brain is a major producer of excitotoxicity and an inducer of oxidative stress. The occurrence of these 2 events is partly responsible for the neuronal damage inherent in patients with mental disorders. In the case of MDD, the release of hormone and increase in pro-inflammatory cytokines in plasma and indicators of oxidative stress have been identified as consequences of this event. The most important affectations in patients with MDD are changes in their cognitive and executive functions due to brain inflammation. Hence, these biomarkers can serve as diagnostic and severity classification tools and treatment. In this work, we described the communication pathway between the immune and neuroendocrine systems in MDD and suggested possible therapeutic options for the disease.

Keywords: Depressive disorder; immune response; inflammatory process; monoamines; oxidative stress; review.

Figure 1.

Stimulation/inhibition mechanisms of hypothalamic-pituitary-adrenal gland (HPA) axis by cortisol. Naturally, there is an inhibitory mechanism carried out by cortisol receptors in the hypothalamus. Nevertheless, in patients with major depressive disorder, this mechanism is inhibited, thus, favoring a hypercortisolemia state.

Figure 2.

Kynurenine pathway. The induction of indolamine 2,3-dioxygenase enzyme through proinflammatory cytokines to catalyze the insertion of 2 oxygen atoms in the pyrrole ring of various indolamines, which include tryptophan, 5-hydroxytriptophan, and serotonin among others. The degradation of serotonin by indolamine 2,3-deoxygenase, called kynurenine derivation, produces formyl-5-hydroxykynurenamine detected in brain of patients with major depressive disorder.

Figure 3.

Simplified scheme of the induction of indolamine 2,3-dioxygenase enzyme and the use of tryptophan towards the synthesis of kynurenine with consequent excitotoxicity.