Kynurenine pathway: the link between depressive disorders and inflammation

Abstract

Depression is highly prevalent worldwide and the leading cause of disability. It is believed that currently more than 300 million people of all ages suffer from depression. However, the unambiguous cause of the depression remains unknown. It is suggested that the occurrence of this disease is primarily affected by genetic factors, psychological factors and atypical brain structure or function. Recently, an increasingly important role is attributed to the inflammatory response, which is considered to be the main cause of depression. Activation of the kynurenine pathway (KP) is one of the described mechanisms by which inflammation can induce depression. Kynurenine pathway activation is associated with several neuropsychiatric diseases, including major depression disorder (MDD). The imbalance between the neuroprotective and neurotoxic metabolites in the kynurenine pathway and the associated serotonin and melatonin deficiency, may contribute to the manifestation of depressive symptoms. In this review we discuss the role of the major enzymes of the tryptophan KP: tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) and the role of selected kynurenic metabolites in the depressive disorders. Particular attention was also paid to the genetic basis of depressive disorders and to the summary of current knowledge on the effectiveness of treatment and supplementation with tryptophan and 5-hydroxytryptophan in depression.