A review of the psychoneuroimmunologic concepts on the etiology of depressive disorders.

The brain is no longer considered an immunoprivileged organ which is completely separated from the circulating immune cells by the blood-brain barrier and which shows a lowered or changed immunoreactivity. It has become clear that there are numerous interactions between the neurological, immune and neuroendocrinologic systems. The psychiatric disorder which is supposed to be connected to changes in the functioning of the immune system is depression. One of the hypotheses suggesting the pathophysiology of depression is the cytokine hypothesis of depression. According to it, the behavior changes in depressed patients are a consequence of changes in cytokines. Physiological and psychological effects of the immune activation during an infection, primarily mediated by central activity of peripherally excreted proinflammatory cytokines, are called "sickness behavior". Depression is connected with the activation of the inflammatory response system. When it comes to the immune characteristics of depressive disorders, it should be stressed that depression is a heterogeneous disorder, so different types of depression can differ not only psychopathologically but also at the immune level. Depression is characterized by disorders in noradrenergic and serotonergic neurotransmission. Proinflammatory cytokines are included in the noradrenergic and serotonergic neurotransmission in the brain areas that are thought to be involved in the pathogenesis of depression. According to this model, depression can be considered a psychoneuroimmune disease in which the peripheral immune activation is responsible (by excreting the inflammatory mediator) for various behavioral, neuroendocrinologic and neurochemical changes connected to the psychiatric condition.