Changes in Tryptophan-Kynurenine Metabolism in Patients with Depression Undergoing ECT—A Systematic Review

Abstract

The kynurenine pathway of tryptophan (Trp) metabolism generates multiple biologically active metabolites (kynurenines) that have been implicated in neuropsychiatric disorders. It has been suggested that modulation of kynurenine metabolism could be involved in the therapeutic effect of electroconvulsive therapy (ECT). We performed a systematic review with aims of summarizing changes in Trp and/or kynurenines after ECT and assessing methodological issues. The inclusion criterium was measures of Trp and/or kynurenines before and after ECT. Animal studies and studies using Trp administration or Trp depletion were excluded. Embase, MEDLINE, PsycInfo and PubMed were searched, most recently in July 2022. Outcomes were levels of Trp, kynurenines and ratios before and after ECT. Data on factors affecting Trp metabolism and ECT were collected for interpretation and discussion of the reported changes. We included 17 studies with repeated measures for a total of 386 patients and 27 controls. Synthesis using vote counting based on the direction of effect found no evidence of effect of ECT on any outcome variable. There were considerable variations in design, patient characteristics and reported items. We suggest that future studies should include larger samples, assess important covariates and determine between- and within-subject variability. PROSPERO (CRD42020187003).

Crosstalk between Exercise-Derived Endocannabinoidome and Kynurenines: Potential Target Therapies for Obesity and Depression Symptoms

“…This participation has been recently supported by therapeutic interventions focused on inflammation, NMDA antagonists (ketamine), and probiotics; in addition to their positive adjuvant effects on depressive symptoms, these positive effects are related to changes in serum KYN [56][57][58]. However, it is also prudent to point out that some established therapeutic measures for the management of depression or refractory depression, such as electroconvulsive therapy or repetitive transcranial magnetic stimulation, have not been shown to significantly affect serum KYN levels; more studies are needed in this regard [59,60]. Furthermore, there is evidence that supports the role of KYN in bipolar disorder, where changes in serum KYN patterns have been documented in relation to the stage of the disease (depression vs. mania) [61], as well as in depression associated with other medical conditions such as post-stroke depression or depression in type 2 diabetes [62,63].…”

The gut microbiota in development and treatment of depression

“…Disturbances in kynurenine metabolism are reflected in a wide range of somatic and psychiatric diseases. 22 In addition, the vagus nerve plays a crucial role in maintaining the continuity of proper MGBA communication. Microorganisms regulate the activation of the vagus nerve, and then the signal is transmitted to the CNS, enabling healthy mental functioning.…”