ArticleJournal of psychiatry & neuroscience : JPN2016
Reduced kynurenine pathway metabolism and cytokine expression in the prefrontal cortex of depressed individuals.
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Article in Journal of psychiatry & neuroscience : JPN, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 5 of them syntheses that pooled it.
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61citing papers in PubMed, 5 pooled it
2.8field-weighted citation impact, top 10% of its field
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Who cites it
61 citing papers in PubMed, 5 syntheses or guidelines pooled it, 94 citations in OpenAlex.
- Multimodal microglial and kynurenine pathway alterations across the affective-psychosis spectrum: a systematic review of patterns, heterogeneity, and dimensional implications.Molecular psychiatry · 2026Pooled it
- Brain Inflammatory Marker Abnormalities in Major Psychiatric Diseases: a Systematic Review of Postmortem Brain Studies.Molecular neurobiology · 2023Pooled it
- Pooled it
- Glial Cell Abnormalities in Major Psychiatric Diseases: A Systematic Review of Postmortem Brain Studies.Molecular neurobiology · 2022Pooled it
- BrainFrontiers in immunology · 2021Pooled it
- Synchronous spectrofluorimetric determination of tryptophan and kynurenine in human plasma using hydroxypropyl-β-cyclodextrin complexation for investigating their role in major depressive disorder.Scientific reports · 2026Article
- Pursuing the elusive biosignature for suicide: a decennial update.Molecular psychiatry · 2026Review
- Kynurenine pathway metabolites are increased in inflammatory depression and decrease with omega-3 treatment.Brain, behavior, & immunity - health · 2026Article
- Kynurenine pathway dysregulation in major depressive disorder: the convergence of excitotoxicity, neuroinflammation, and oxidative stress.Journal of neuroinflammation · 2026Review
- Re-Examination of Inflammation in Major Depressive Disorder: Bridging Systemic and Neuroinflammatory Insights.Biomolecules · 2025Review
- Epigenetics and immunology: Under-recognized aspects of suicidality.World journal of psychiatry · 2025Review
- Dysregulation of lipid metabolism, energy production, and oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome, Gulf War Syndrome and fibromyalgia.Frontiers in neuroscience · 2025Review
- Correlation linking illness perception, negative emotions, and the post-operative recovery effect in patients with perianal disease.World journal of psychiatry · 2024Article
- Gene expression of kynurenine pathway enzymes in depression and following electroconvulsive therapy.Acta neuropsychiatrica · 2024Article
- Neuroactive Kynurenines as Pharmacological Targets: New Experimental Tools and Exciting Therapeutic Opportunities.Pharmacological reviews · 2024Review
- Molecular profiling of the hippocampus of children with autism spectrum disorder.Molecular psychiatry · 2024Article
- Targeting Large-Conductance Calcium-Activated Potassium Channels to Ameliorate Lipopolysaccharide-Induced Depressive-Like Behavior in Mice.Neurochemical research · 2024Article
- Sex- and suicide-specific alterations in the kynurenine pathway in the anterior cingulate cortex in major depression.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Psychiatric Comorbidities of Inflammatory Bowel Disease: It Is a Matter of Microglia's Gut Feeling.Cells · 2024Review
- The major biogenic amine metabolites in mood disorders.Frontiers in psychiatry · 2024Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 1 country.
Sarah M ClarkFrom the Laboratory of Behavioral Neuroimmunology, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD (Clark, Nicholson, Tonelli); the Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD (Pocivavsek, Notarangelo, McMahon, Schwarcz); the Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD (Langenberg); the Section on Neuropathology, Clinical Brain Disorders Branch, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (Kleinman, Hyde); the Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD (Kleinman, Hyde); and the Mood and Anxiety Program, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD (Stiller, Postolache).
Ana PocivavsekFrom the Laboratory of Behavioral Neuroimmunology, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD (Clark, Nicholson, Tonelli); the Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD (Pocivavsek, Notarangelo, McMahon, Schwarcz); the Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD (Langenberg); the Section on Neuropathology, Clinical Brain Disorders Branch, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (Kleinman, Hyde); the Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD (Kleinman, Hyde); and the Mood and Anxiety Program, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD (Stiller, Postolache).
James D NicholsonFrom the Laboratory of Behavioral Neuroimmunology, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD (Clark, Nicholson, Tonelli); the Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD (Pocivavsek, Notarangelo, McMahon, Schwarcz); the Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD (Langenberg); the Section on Neuropathology, Clinical Brain Disorders Branch, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (Kleinman, Hyde); the Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD (Kleinman, Hyde); and the Mood and Anxiety Program, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD (Stiller, Postolache).
Francesca M NotarangeloFrom the Laboratory of Behavioral Neuroimmunology, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD (Clark, Nicholson, Tonelli); the Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD (Pocivavsek, Notarangelo, McMahon, Schwarcz); the Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD (Langenberg); the Section on Neuropathology, Clinical Brain Disorders Branch, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (Kleinman, Hyde); the Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD (Kleinman, Hyde); and the Mood and Anxiety Program, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD (Stiller, Postolache).
Patricia LangenbergFrom the Laboratory of Behavioral Neuroimmunology, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD (Clark, Nicholson, Tonelli); the Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD (Pocivavsek, Notarangelo, McMahon, Schwarcz); the Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD (Langenberg); the Section on Neuropathology, Clinical Brain Disorders Branch, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (Kleinman, Hyde); the Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD (Kleinman, Hyde); and the Mood and Anxiety Program, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD (Stiller, Postolache).
Robert P McMahonFrom the Laboratory of Behavioral Neuroimmunology, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD (Clark, Nicholson, Tonelli); the Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD (Pocivavsek, Notarangelo, McMahon, Schwarcz); the Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD (Langenberg); the Section on Neuropathology, Clinical Brain Disorders Branch, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (Kleinman, Hyde); the Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD (Kleinman, Hyde); and the Mood and Anxiety Program, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD (Stiller, Postolache).
Joel E KleinmanFrom the Laboratory of Behavioral Neuroimmunology, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD (Clark, Nicholson, Tonelli); the Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD (Pocivavsek, Notarangelo, McMahon, Schwarcz); the Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD (Langenberg); the Section on Neuropathology, Clinical Brain Disorders Branch, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (Kleinman, Hyde); the Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD (Kleinman, Hyde); and the Mood and Anxiety Program, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD (Stiller, Postolache).
Thomas M HydeFrom the Laboratory of Behavioral Neuroimmunology, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD (Clark, Nicholson, Tonelli); the Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD (Pocivavsek, Notarangelo, McMahon, Schwarcz); the Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD (Langenberg); the Section on Neuropathology, Clinical Brain Disorders Branch, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (Kleinman, Hyde); the Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD (Kleinman, Hyde); and the Mood and Anxiety Program, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD (Stiller, Postolache).
John StillerFrom the Laboratory of Behavioral Neuroimmunology, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD (Clark, Nicholson, Tonelli); the Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD (Pocivavsek, Notarangelo, McMahon, Schwarcz); the Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD (Langenberg); the Section on Neuropathology, Clinical Brain Disorders Branch, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (Kleinman, Hyde); the Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD (Kleinman, Hyde); and the Mood and Anxiety Program, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD (Stiller, Postolache).
Teodor T PostolacheFrom the Laboratory of Behavioral Neuroimmunology, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD (Clark, Nicholson, Tonelli); the Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD (Pocivavsek, Notarangelo, McMahon, Schwarcz); the Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD (Langenberg); the Section on Neuropathology, Clinical Brain Disorders Branch, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (Kleinman, Hyde); the Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD (Kleinman, Hyde); and the Mood and Anxiety Program, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD (Stiller, Postolache).
Robert SchwarczFrom the Laboratory of Behavioral Neuroimmunology, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD (Clark, Nicholson, Tonelli); the Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD (Pocivavsek, Notarangelo, McMahon, Schwarcz); the Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD (Langenberg); the Section on Neuropathology, Clinical Brain Disorders Branch, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (Kleinman, Hyde); the Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD (Kleinman, Hyde); and the Mood and Anxiety Program, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD (Stiller, Postolache).
Leonardo H TonelliFrom the Laboratory of Behavioral Neuroimmunology, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD (Clark, Nicholson, Tonelli); the Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD (Pocivavsek, Notarangelo, McMahon, Schwarcz); the Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD (Langenberg); the Section on Neuropathology, Clinical Brain Disorders Branch, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (Kleinman, Hyde); the Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD (Kleinman, Hyde); and the Mood and Anxiety Program, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD (Stiller, Postolache).
Lieber Institute for Brain Development · USNational Institutes of Health · USUniversity of Maryland, Baltimore · USNational Institute of Mental Health · US
Funding
The Effects of Kynurenine Aminotransferase Inhibition in People with SchizophreniaP50MH103222 · NIMH · UNIVERSITY OF MARYLAND BALTIMORE · PI SCHWARCZ, ROBERT · 2014 to 2023
$25.2MEndogenous Kynurenic Acid Modulates Prefrontal ACh Levels and Cognitive BehaviorR01MH083729 · NIMH · OHIO STATE UNIVERSITY · PI BRUNO, JOHN P, SCHWARCZ, ROBERT · 2010 to 2014
$1.8MNeuroimmune Mechanisms of Risk and Resilience to Maladaptive Responses to StressR01MH097676 · NIMH · UNIVERSITY OF MARYLAND BALTIMORE · PI TONELLI, LEONARDO H · 2011 to 2014
$1.5MNIMH NIH HHS P50 MH103222NIMH NIH HHS R01 MH083729NIMH NIH HHS R01 MH097676
Abstract
backgroundNeuroinflammatory processes are increasingly believed to participate in the pathophysiology of a number of major psychiatric diseases, including depression. Immune activation stimulates the conversion of the amino acid tryptophan to kynurenine, leading to the formation of neuroactive metabolites, such as quinolinic acid and kynurenic acid. These compounds affect glutamatergic neurotransmission, which plays a prominent role in depressive pathology. Increased tryptophan degradation along the kynurenine pathway (KP) has been proposed to contribute to disease etiology.
methodsWe used postmortem brain tissue from the ventrolateral prefrontal cortex (VLPFC) to assess tissue levels of tryptophan and KP metabolites, the expression of several KP enzymes and a series of cytokines as well as tissue pathology, including microglial activation. Tissue samples came from nonpsychiatric controls (
resultsWe found a reduction in the enzymatic conversion of tryptophan to kynurenine, determined using the kynurenine:tryptophan ratio, and reduced messenger RNA expression of the enzymes indoleamine-2,3-dioxygenase 1 and 2 and tryptophan-2,3-dioxygenase in depressed individuals irrespective of the cause of death. These findings correlated with reductions in the expression of several cytokines, including interferon-γ and tumour necrosis factor-α. Notably, quinolinic acid levels were also lower in depressed individuals than controls. LIMITATIONS: Information on the use of antidepressants and other psychotropic medications was insufficient for statistical comparisons.
conclusionContrary to expectations, the present results indicate that depression, in the absence of medical illness or an overt inflammatory process, is associated with compromised, rather than increased, KP metabolism in the VLPFC.
Indexed as
AdultCytokinesDepressive DisorderFemaleHumansImmunohistochemistryKynurenineMalePolymerase Chain ReactionPrefrontal CortexRNA, MessengerCytokinesKynurenineRNA, Messenger
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