Kynurenines: from the perspective of major psychiatric disorders

• Published in: The FEBS journal 2012-04, Vol.279 (8), p.1375-1385
• Main Author: Myint, Aye M.
• Format: Article
• Language: English
• Subjects: Amino acids; Animals; Biomarkers; bipolar; Bipolar Disorder - drug therapy; Bipolar Disorder - metabolism; Bipolar Disorder - pathology; Brain; depression; Depressive Disorder, Major - drug therapy; Depressive Disorder, Major - metabolism; Depressive Disorder, Major - pathology; Humans; inflammation; kynurenic acid; kynurenine; Kynurenine - metabolism; Mental disorders; Neurochemistry; NMDA; Plasma; psychiatry; quinolinic acid; schizophrenia; Schizophrenia - drug therapy; Schizophrenia - metabolism; Schizophrenia - pathology; tryptophan
• ISSN: 1742-464X; 1742-4658
• DOI: 10.1111/j.1742-4658.2012.08551.x

Psychiatric disorders are documented to be associated with a mild pro‐inflammatory state. Pro‐inflammatory mediators could activate the tryptophan breakdown and kynurenine pathway with a shift toward the neurotoxic arm where excitotoxic N‐methyl‐d‐aspartate receptor agonist quinolinic acid is formed. An unbalanced metabolism in terms of neuroprotective and neurotoxic effects, such as reduced kynurenic acid to kynurenine ratio, has been demonstrated in the major psychiatric disorders such as unipolar depression, bipolar manic‐depressive disorder and schizophrenia, and in drug‐induced neuropsychiatric side effects such as interferon‐α treated patients. The changes in serum or plasma are shown to be associated with central changes such as in the cerebrospinal fluid and certain brain areas. While currently available antidepressants and mood stabilizers could not efficiently improve these neurochemical changes within the same period that could induce clinical improvement, some antipsychotic treatments could reverse certain metabolic imbalances. Some of these changes were tested also in animal models. In this review the role of this unbalanced kynurenine metabolism through interactions with other neurochemicals is discussed as a major contributing pathophysiological mechanism in psychiatric disorders. Moreover, the biomarker role of kynurenine metabolites and future therapeutic opportunities are also discussed. This minireview discussed the role of kynurenine pathway metabolites in major psychiatric disorders such as major depression, bipolar disorders and schizophrenia, from the aspects of interaction of kynurenines with other neurochemicals in the brain, interaction of kynurenines in the body and brain through immune activation, clinical implication of kynurenines in these disorders and future perspectives regarding therapeutics and diagnostics