Brain inflammation hypothesis in depression and its potential as a therapeutic target

Abstract

 Most of the current depression drugs have been developed based on the monoamine hypothesis. However, about 30% of patients indicate resistance to medication, and patients with relatively mild depression get only a small benefit from antidepressants. In addition, although an increase in monoamine concentration in synaptic gaps by monoamine transporter inhibition occurs within a relatively short time, it takes about six weeks to show an antidepressant effect in actual clinical settings. There are cases in which an antidepressant effect is observed for drugs that do not regulate the amount of monoamine. These facts suggest the presence of a variety of pathophysiologies in depression and depressive symptoms. Recently, a relationship between the onset of depression and the expression levels of immune-related molecules such as cytokines in the blood and the brain derived from patients with depression has been pointed out. Although there is so far no medication targeting neuroinflammation, many recent studies have shown that inflammation is not negligible and a significant factor in the pathogenesis of depression. Therefore, it is meaningful to focus on inflammation for elucidating the pathogenesis and developing medications. In this paper, we describe the pathogenesis pathways known to be involved in the inflammation, the serotonin hypothesis, hypothalamic-pituitary-adrenal axis hypothesis, and neurodegeneration/neurogenesis hypothesis and describe the applications to therapy and preventions based on them.