Violation of the concentration of norepinephrine, dopamine, serotonin underlies depression. This conclusion was made as a result of experiments on the action of antidepressants. But two more mediators: gamma- aminobutyric acid and glutamate are involved in the mechanism of the development of depression. Lamotrigine , ketamine, amantadine and anticonvulsants affect the severity of depression by affecting the glutamate receptors .
Stress also plays an important role in the development of depression, especially the first episode. The reason for this is the dysregulation of the hypothalamic-pituitary-adrenal axis. With depression, the level of the adrenal hormone cortisol is increased, which did not decrease with the introduction of dexamethasone. This fact formed the basis for the creation of the dexamethasone test, which is used to identify “endogenous depression”. Dysfunction of the hypothalamic-pituitary-adrenal axis is associated with an imbalance of the corticotropin- resisting factor. Patients who have elevated levels of corticotropin- releasing factor have decreased pituitary response to release ACTH. A decrease in the secretion of the corticotropin- releasing factor c reduces the severity of the pituitary response in terms of the secretion of ACTH, then cortisol, with the infusion of a synthetic corticotropin- releasing factor. Dexamethasone stress is an indicator of remission .
Childhood trauma contributes to the susceptibility to stress, the development of depression, since the regulation of the hypothalamic-pituitary-adrenal axis is disturbed. Moreover, children are prone to hyperactivity during critical periods of brain development, which is reflected in a predisposition to depression throughout life. Disturbances in the hypothalamic-pituitary axis lead to an increase in the release of glucocorticoids. As a consequence , structural and functional changes occur in the limbic system in depressed patients. Antidepressant treatment reduces cell proliferation in this region of the brain. Impaired neurotransmitter function and changes in the hypothalamic-pituitary axis also lead to changes in neuroplasticity . There is also a family (hereditary) predisposition to depression.