The tryptophan catabolite or kynurenine pathway in autism spectrum disorder; a systematic review and meta-analysis

Abstract

Background: Autism spectrum disorder (ASD) is a neurodevelopment disorder characterized by impaired social communication and interaction, as well as rigid and unchanging interests and behaviors. In ASD, studies show activated immune-inflammatory and nitro-oxidative pathways which are accompanied by depletion of plasma tryptophan (TRP), increased competing amino acids (CAAs) and activation of the TRP catabolite (TRYCAT) pathway. Objectives: This study aims to systematically review and meta-analyze data on peripheral TRP, CAAs, TRYCAT pathway activity, and individual TRYCATs, including kynurenine (KYN) and kynurenic acid (KA) levels, in blood and urine of ASD patients. Methods: After searching PubMed, Google Scholar, and SciFinder extensively, a total of 25 full-text papers were included in the analysis, with a total of 6653 participants (3,557 people with ASD and 30,96 healthy controls). Results: Blood TRP and the TRP/CAAs ratio were not significantly different between ASD patients and controls (standardized mean difference, SMD= -0.227, 95% confidence interval, CI: -0.540; 0.085 and SMD= 0.158, 95%CI: -0.042; 0.359) respectively. The KYN/TRP ratio showed no significant difference between ASD and controls (SMD= 0.001, 95%CI: -0.169; 0.171). Blood KYN and KA levels were not significantly changed in ASD. Moreover, there were no significant differences in urine TRP, KYN and KA levels between ASD and controls. We could not establish increases in neurotoxic TRYCATs in ASD. Conclusions: Our study demonstrates that there are no abnormalities in peripheral blood TRP metabolism, IDO activity, and TRYCAT production in ASD. Reduced TRP availability and elevated neurotoxic TRYCAT levels are not substantial contributors to ASD's pathophysiology.