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Review
. 2024 Jan 19;13(2):583.
doi: 10.3390/jcm13020583.

The Kynurenine Pathway in Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analysis of Blood Concentrations of Tryptophan and Its Catabolites

Daniele Cavaleri  1 , Cristina Crocamo  1 , Pietro Morello  1 , Francesco Bartoli  1 , Giuseppe Carrà  1   2
Affiliations
Review

The Kynurenine Pathway in Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analysis of Blood Concentrations of Tryptophan and Its Catabolites

Daniele Cavaleri et al. J Clin Med. .

Abstract

Preliminary evidence shows that the kynurenine pathway (KP) may be altered in attention-deficit/hyperactivity disorder (ADHD). We thus conducted a systematic review and meta-analysis exploring the peripheral blood concentrations of tryptophan catabolites (TRYCATs) in people with ADHD. We searched the main electronic databases up to 7th December 2023. Standardised mean differences (SMDs) with 95% confidence intervals (95%CIs) were used to compare TRYCAT concentrations between participants with ADHD and healthy controls (HCs). We included eight studies. Random-effects meta-analyses found higher kynurenine (SMD = 0.56; 95%CI: 0.04 to 1.08; p = 0.033; I2 = 90.3%) and lower kynurenic acid (SMD = -0.33; 95%CI: -0.49 to -0.17; p < 0.001; I2 = 0%) concentrations in people with ADHD compared to HCs. Additional analyses on drug-free children with ADHD showed higher tryptophan (SMD = 0.31; 95%CI: 0.11 to 0.50; p = 0.002; I2 = 0%) and kynurenine (SMD = 0.74; 95%CI: 0.30 to 1.17; p < 0.001; I2 = 76.5%), as well as lower kynurenic acid (SMD = -0.37; 95%CI: -0.59 to -0.15; p < 0.001; I2 = 0%) blood levels, as compared to HCs. Despite some limitations, our work provides preliminary evidence on KP alterations in ADHD that may suggest decreased neuroprotection. Further research is needed to clarify the role of the KP in ADHD.

Keywords: attention-deficit/hyperactivity disorder; kynurenic acid; kynurenine pathway; meta-analysis; peripheral blood; systematic review; tryptophan catabolism.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
PRISMA flow chart of the inclusion process.
Figure 2
Figure 2
Effect sizes of the differences in peripheral blood concentrations of tryptophan and its catabolites between individuals with attention-deficit/hyperactivity disorder and healthy controls. Darker bars represent effect sizes of overall meta-analyses. Lighter bars represent effect sizes of meta-analyses in drug-free children. Error bars represent 95% confidence interval. * p < 0.05; ** p < 0.01; *** p < 0.001. 3HAA = 3-hydroxyanthranilic acid; 3HK = 3-hydroxykynurenine; AA = anthranilic acid; ADHD = attention-deficit/hyperactivity disorder; KYN = kynurenine; KYNA = kynurenic acid; TRP = tryptophan.
See this image and copyright information in PMC

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