Evidence map›Paper›PMID 34266671›Full record

ReviewBiological psychiatry2022

The Kynurenine Pathway in Traumatic Brain Injury: Implications for Psychiatric Outcomes.

Timothy B Meier, Jonathan Savitz

Registry-linked trialOpen access · greenAbstract readReview
In one paragraph

Review in Biological psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06821087 (Evaluating the Neuromodulatory Effect of Ketamine in Long COVID), which is not on this map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
3.3field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT06821087 phase2completednot on this mapstarted 2025, after this paper: background citation

Evaluating the Neuromodulatory Effect of Ketamine in Long COVID: A Pilot Study Targeting Fatigue and Neurocognitive Symptoms

TypeinterventionalSponsorUniversity of Texas at AustinRan2025 to 2026Enrolled20ConditionsLong COVIDArmsKetamine only
3 · Its place in the literature

Who cites it

45 citing papers in PubMed, 68 citations in OpenAlex.

  1. Article
  2. Toll like receptor 4 (TLR4) in neuroinflammation: From acute hemorrhagic stroke to chronic neurodegeneration.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 2 institutions in 1 country.

Timothy B MeierDepartment of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin; Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee, Wisconsin; Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin. Electronic address: tmeier@mcw.edu.
Jonathan SavitzLaureate Institute for Brain Research, Tulsa, Oklahoma; Oxley College of Health Sciences, The University of Tulsa, Tulsa, Oklahoma.
Laureate Institute for Brain Research · USMedical College of Wisconsin · US

Funding

The role of neuroactive kynurenine metabolites in the chronic sequelae of concussion and contact sport exposureR01NS102225 · NINDS · MEDICAL COLLEGE OF WISCONSIN · PI MEIER, TIMOTHY B. · 2018 to 2022
$1.8M
Acute modulation of neural circuitry regulating immune function in depressionR21MH113871 · NIMH · LAUREATE INSTITUTE FOR BRAIN RESEARCH · PI SAVITZ, JONATHAN · 2018 to 2019
$477k
NIMH NIH HHS R21 MH113871NINDS NIH HHS R01 NS102225
6 · The paper itself

Abstract

Traumatic brain injury (TBI) is an established risk factor for the development of psychiatric disorders, especially depression and anxiety. However, the mechanistic pathways underlying this risk remain unclear, limiting treatment options and hindering the identification of clinically useful biomarkers. One salient pathophysiological process implicated in both primary psychiatric disorders and TBI is inflammation. An important consequence of inflammation is the increased breakdown of tryptophan to kynurenine and, subsequently, the metabolism of kynurenine into several neuroactive metabolites, including the neurotoxic NMDA receptor agonist quinolinic acid and the neuroprotective NMDA receptor antagonist kynurenic acid. Here, we review studies of the kynurenine pathway (KP) in TBI and examine their potential clinical implications. The weight of the literature suggests that there is increased production of neurotoxic kynurenines such as quinolinic acid in TBI of all severities and that elevated quinolinic acid concentrations in both the cerebrospinal fluid and blood are a negative prognostic indicator, being associated with death, magnetic resonance imaging abnormalities, increased depressive and anxiety symptoms, and prolonged recovery. We hypothesize that an imbalance in KP metabolism is also one molecular pathway through which the TBI-induced neurometabolic cascade may predispose to the development of psychiatric sequelae. If this model is correct, KP metabolites could serve to predict who is likely to develop psychiatric illness while drugs that target the KP could help to prevent or treat depression and anxiety arising in the context of TBI.

Indexed as

Brain Injuries, TraumaticKynurenineHumansInflammationQuinolinic AcidReceptors, N-Methyl-D-AspartateKynurenineQuinolinic AcidReceptors, N-Methyl-D-AspartateConcussionDepressionInflammationKynureninePsychiatricTBI

Identifiers

PMID34266671
PMCPMC8630076
OpenAlexW3168252635

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.