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

Background: Indoleamine 2,3-dioxygenase (IDO) activity is induced by cellular immune activation and therefore associated with 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 in the findings of studies investigating KYN/TRP in severe mental disorders. Although there are hints that inflammation associated with TRP catabolism towards the KYN pathway via elevated IDO activity seems likely, no conclusive statements can be drawn. Presumably, the consideration of influencing factors such as inflammatory processes, metabolic activities and psychological/neuropsychiatric symptoms are pivotal for a deeper understanding of the underlying mechanisms.