Network beyond IDO in psychiatric disorders: revisiting neurodegeneration hypothesis

Abstract

The involvement of immune system activation in the pathophysiology of certain psychiatric disorders is well documented. Inflammatory molecules such as pro-inflammatory cytokines could enhance the activity of the indoleamine 2,3-dioxygenase (IDO) enzyme which is the first rate-limiting enzyme of the tryptophan degradation pathway, the kynurenine pathway. The increased tryptophan degradation could induce serotonin depletion and depressive mood. On the other hand, the downstream metabolites from this pathway, such as 3-hydroxykynurenine, quinolinic acid and kynurenic acid, are neuroactive metabolites which can modulate several neurotransmissions, such as glutamatergic, GABAergic, dopaminergic and noradrenergic neurotransmissions, which in turn induce changes in neuronal-glial network and neuropsychiatric consequences. In this issue, we have revised the previous 'neurodegeneration hypothesis,' which explained the involvement of cytokines and IDO pathway interaction in depression, with a further extended view related to the network beyond IDO, the network between immune molecules, tryptophan metabolites and different neurotransmitters, in depression and other major psychiatric disorders such as schizophrenia, bipolar disorder and childhood psychiatric disorders.

Keywords: 3-hydroxy-anthranillic acid oxidase; 3-hydroxy-kynurenine; 3-hydroxyanthranilic acid; 3HK; 5-hydroxy indole; 5-hydroxyindole acetic acid; 5HI; 5HIAA; ACC; ADHD; AFMK; ATP; Ach; BBB; BCG; Bipolar; CSF; DA; Depression; GABA; Glutamate; HAA; HAAO; HO1; HPA; IDO; IFN; IL1; KATs; KMO; KYN; KYNA; Kynurenine; MAO; MR; N-acetyl-N-formyl-5methoykynuramine; N-methyl-D-aspartate; NA; NAD; NMDA; NMDA receptor; NMDA-R; PGE2; PIC; QUIN; SSRI; Schizophrenia; T helper; TDO; TRP; Th; a7-nicotinic acetylcholine receptor; a7nAchR; aMCC; acetylcholine; adenosine triphosphate; anterior cingulate cortex; anterior mid cingulate cortex; attention deficit hyperactive disorder; bacille Calmette-Guérin; blood-brain-barrier; cerebrospinal fluid; dopamine; f5OHKYM; formyl-5-hydroxykynuramine; gamma-aminobutyric acid; hemeoxygenase 1; hypothalamo-pituitary-adrenal; indoleamine 2,3-dioxygenase; interferon; interleukin; kynurenic acid; kynurenine; kynurenine aminotransferases; kynurenine-3-monooxygenase; magnetic resonance; monoamine oxidase; nicotinamide adenine dinucleotide; noradrenaline; picolinic acid; prostaglandin E2; quinolinic acid; selective serotonin reuptake inhibitor; tryptophan; tryptophan 2,3-dioxygenase.