M2. Kynurenic Acid in Schizophrenia: A Systematic Review and Meta-analysis
Bibliographic record
Abstract
Background: Kynurenic acid (KYNA) is an endogenous antagonist of N-methyl-D-aspartate and α7 nicotinic acetylcholine receptors that is derived from astrocytes as part of the kynurenine pathway of tryptophan degradation. Mounting evidence suggests that abnormal KYNA levels are involved in the pathophysiology of schizophrenia (SCZ). Although individual studies have shown deviations in KYNA levels in patients with SCZ, their findings have not been assessed through a meta-analysis. The primary purpose of this systematic review and meta-analysis was to evaluate the difference in KYNA levels between patients with SCZ and healthy controls (HCs). Methods: A literature search was conducted through Ovid using Embase, Medline, and PsycINFO databases (last search: January 2016) with the search terms: (kynuren* or KYNA) and (schizophreni* or psychosis). English language studies investigating KYNA levels in patients with SCZ and in HCs were identified. The difference in KYNA levels between patients with SCZ and HCs was determined by calculating standardized mean differences. Subgroup analyses were separately performed for KYNA measurement technique and KYNA sample source. Results: The search yielded 295 publications and 11 studies were included in the meta-analysis. In the main analysis, KYNA levels were elevated in patients with SCZ compared to HCs. Subgroup analyses demonstrated that KYNA levels were increased in the patient group within cerebrospinal fluid and brain tissue samples, and centrally but not peripherally. Conclusion: Taken together, KYNA levels are increased in patients with SCZ, although elevations appear to be localized to the central nervous system. To better wholly assess findings from heterogeneous study designs, future investigations should focus on elucidating the relationships among KYNA levels within cerebrospinal fluid, brain tissue, plasma, and saliva in patients with SCZ. Overall, an improved understanding of KYNA in patients with SCZ may contribute to the development of novel diagnostic approaches and therapeutic strategies.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.010 | 0.022 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.015 | 0.037 |
| Bibliometrics | 0.008 | 0.009 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.008 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".