The kynurenine pathway in major depressive disorder, bipolar disorder, and schizophrenia: a systematic review and meta-analysis of cerebrospinal fluid studies.
Level 3 - non-randomized controlled study
Systematic review and meta-analysis of observational case-control studies
PubMed 37127280 · doi:10.47626/1516-4446-2022-2973
What was done
A systematic review and meta-analysis was conducted according to PRISMA guidelines searching PubMed and Scopus through April 2022. The authors included case-control studies comparing cerebrospinal fluid (CSF) concentrations of kynurenine pathway metabolites—tryptophan (TRP), kynurenine (KYN), kynurenic acid (KA), quinolinic acid (QA), and 3-hydroxykynurenine (3-HK)—between healthy controls and individuals diagnosed with schizophrenia (SZ), bipolar disorder (BD), or major depressive disorder (MDD). Standardized mean differences (SMD) were calculated using random-effects models.
What was found
Twenty-three articles were included (SZ k = 8, BD k = 8, MDD k = 11). In schizophrenia, CSF KA levels were significantly elevated compared to controls (SMD = 2.64, 95% CI 1.16 to 4.13, p = 0.0005, I2 = 96%, k = 6, n = 384), whereas TRP (k = 5) and KYN (k = 4) showed no significant differences. In bipolar disorder, TRP levels did not differ significantly from controls (k = 7). In major depressive disorder, no metabolite reached statistically significant differences overall; KA and QA showed elevated trends but only had two studies each (k = 2), limiting statistical evaluation.
Why it matters
This review synthesizes direct central nervous system evidence for kynurenine pathway dysregulation across major psychiatric illnesses, confirming elevated kynurenic acid in schizophrenia while finding insufficient evidence for stable alterations in major depression and bipolar disorder.
Limits
The positive finding for kynurenic acid in schizophrenia exhibited severe heterogeneity (I2 = 96%). Most metabolite comparisons in depression and bipolar disorder were constrained by very few published studies (often k = 2 to 7), preventing firm conclusions. Total sample sizes and patient clinical characteristics (such as medication status and disease stage) were not reported for most analyses in the abstract.
Cited by
- partial Kynurenic acid and quinolinic acid are neurotoxic serotonin/tryptophan pathway metabolites associated with brain inflammation.