Previously, scientists and doctors believed that neurotransmitters – monoamines, in particular serotonin, dopamine, norepinephrine – play a role in the genesis of depression . This hypothesis arose under the influence of the results of research on antidepressants, but today two more mediators deserve attention – glutamate , which regulates excitation processes, and gamma- aminobutyric acid (GABA), the main mediator of inhibition.
This is supported by evaluations of the effects of ketamine, amantadine , lamotrigine, and anticonvulsants on the severity of depression. These drugs act on the NMDA (N – methyl – D – aspartate ) glutamate receptors.
The factors that provoke stress play an important role in the development of depression, especially the stress factor is important in the first episode of depression. A person’s predisposition to the effects of stress factors depends on disorders in the regulation of the hypothalamic-pituitary-adrenal system.
Some researchers have found elevated levels of the adrenal hormone cortisol in a large number of depressed patients who have not yet received drug therapy. Moreover, the level of cortisol did not decrease after the administration of dexamethasone. This effect formed the basis for the creation of the dexamethasone test, which was introduced into clinical practice. It detects endogenous depression.
Disturbances in the regulation of the hypothalamic-pituitary-adrenal system occur primarily at the level of secretion of corticotropin- releasing hormone (CRH), which promotes the secretion of adrenocorticotropic hormone (ACTH). A decrease in the level of CRH secretion in patients with high CRH values reduces the production of ACTH by the pituitary gland and subsequently cortisol. A decrease in CRH secretion occurs in response to the introduction of synthetic CRH.
The remissions that occur after episodes of depression can be traced by the dexamethasone test.
Adults who have suffered severe psychological trauma in childhood are vulnerable to stress, which means to the development of depression, since they have impaired regulation of the hypothalamic-pituitary-adrenal system. Such patients have a tendency to be hyperactive, especially during critical periods of brain development, and a predisposition to depression throughout life, especially in the presence of stress. Numerous changes in the hypothalamic-pituitary-adrenal system, leads to an increase in the secretion of glucorticoids , which leads to structural and functional changes in the limbic system in patients with depression. Antidepressant therapy leads to a decrease in the proliferation of cells in the limbic system of the brain. The modern approach to the genesis of depression does not exclude the role of neuroplasticity in the development of depression. The role of hereditary factors in the development of depression was also noted.