Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

The Tryptophan Catabolite or Kynurenine Pathway’s Role in Major Depression

Version 1 : Received: 2 January 2022 / Approved: 11 January 2022 / Online: 11 January 2022 (10:39:25 CET)

How to cite: Almulla, A.F.; Maes, M. The Tryptophan Catabolite or Kynurenine Pathway’s Role in Major Depression. Preprints 2022, 2022010134 (doi: 10.20944/preprints202201.0134.v1). Almulla, A.F.; Maes, M. The Tryptophan Catabolite or Kynurenine Pathway’s Role in Major Depression. Preprints 2022, 2022010134 (doi: 10.20944/preprints202201.0134.v1).

Abstract

Kynurenine or tryptophan catabolite (TRYCAT) pathway contributes to the pathophysiology of major depression disorder (MDD) and major depressive episodes (MDE) in bipolar disorder and suicidal behaviors. The consequences of the overactivation of this pathway large reduced tryptophan (TRP) levels in peripheral blood and the CNS and increased levels of neurotoxic TRYCATs including kynurenine (KYN), 3-hydroxy kynurenine (3HK), quinolinic acid (QA), xanthurenic acid (XA), and picolinic acid (PA). However, other TRYCATs are protective, such as kynurenic acid (KA) and anthranilic acid (AA). Inflammation and cell-mediated immune activation along with oxidative and nitrosative stress (O&NS) may stimulate the first and rate-limiting enzyme of this pathway, namely indoleamine-2,3-dioxygenase (IDO). Therefore, during depression, balancing neuroprotective versus neurotoxic TRYCATs and balancing activation of the immune response system (IRS) versus the compensatory immune response system is crucial for achieving better treatment outcomes. Furthermore, targeting the causes of TRYCAT pathway activation (immune activation and O&NS) is probably the most effective strategy to treat depression. In the present review, we aim to provide a comprehensive explanation of the impact of TRYCATs in terms of pathophysiology and treatment of MDD and MDE.

Keywords

TRYCATs; MDD; MDE; Suicidal behavior; Kynurenine pathway

Subject

MEDICINE & PHARMACOLOGY, Psychiatry & Mental Health studies

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our diversity statement.

Leave a public comment
Send a private comment to the author(s)
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.