Indoleamine 2,3-dioxygenase (IDO)-activity in Severe Psychiatric Disorders: A Systemic Review

Abstract

Background: Indoleamine 2,3-dioxygenase (IDO) activity is induced by cellular immune activation and therefore associated to inflammatory diseases, among others psychiatric disorders. This review aims to elucidate IDO activity reflected by kynurenine (KYN) to tryptophan (TRP) ratio in severe mental disorders. Methods: A systematic literature search in MEDLINE and EMBASE was conducted targeting clinical trials in English language measuring KYN/TRP in individuals with a diagnosis of depression, bipolar disorder, or schizophrenia. Results: Five out of 15 studies found higher levels of KYN/TRP in depression compared to a control group while the same amount found no difference. Moreover, three studies showed lower levels. In bipolar disorder, four out of six and in psychotic disorders three out of four trials found higher levels in patients compared to controls. There are only two studies comparing KYN/TRP in major depression and bipolar disorder, showing conflicting results. Eight studies focused on associations between KYN/TRP and clinical parameters, whereas two studies found positive correlations between KYN/TRP and severity of depressive symptoms. In contrast, four studies did not show an association. IDO activity during specific psychiatric treatment was analyzed by eight studies. Conclusion: In summary, this review demonstrates an inconsistency of findings of studies investigating KYN/TRP in severe mental disorders. Although there are hints that inflammation associated TRP catabolism towards the KYN pathway via elevated IDO activity seems likely, no conclusive statements can be drawn. Presumably, the consideration of influencing factors as inflammatory processes, metabolic activities and psychological/neuropsychiatric symptoms are pivotal for a deeper understanding of the underlying mechanisms.

Ferulic Acid: A Review of Pharmacology, Toxicology, and Therapeutic Effects on Pulmonary Diseases

“…The gene expression of indoleamine 2,3-dioxygenase (IDO) is determined by p38 MAPK, and the activity is induced by cellular immune activation associated with inflammatory diseases [68]. LPS induces the expression of IDO, and FA can pass through the blood-brain barrier to reduce IDO by suppressing the phosphorylation of p38 MAPK, which may provide new ideas for the prevention and treatment of diseases [69].…”

The protective role of ginsenoside Rg3 in heart diseases and mental disorders

“…In cardiac disease management, Rg3 chiefly functions by reducing inflammation and curtailing oxidative stress. Anti-inflammatory action is linked to the regulation of TRP/KYN metabolism, enhancing 5-HT and BDNF levels, and thereby alleviating mental disorders ( Kuo et al, 2021 ; Fellendorf et al, 2022 ; Gong et al, 2023 ). MDD is characterized by reduced antioxidant concentrations in plasma ( Bhatt et al, 2020 ).…”

Indoleamine 2,3-Dioxygenase (IDO) Activity: A Perspective Biomarker for Laboratory Determination in Tumor Immunotherapy

“…Recent studies have reported that IDO activity, as reflected by Kyn/Trp ratio, shows significant differences in different types of mental disorders. However, the results of studies on Kyn/Trp calculations for severe mental disorders are inconsistent [82]. Therefore, with the important involvement of IDO in various vital metabolic activities, it is necessary to summarize the currently available methods for the determination of IDO activity, hoping to find a suitable method for the determination of IDO activity to be applied in clinical diagnosis and treatment.…”