Cited by 96Tryptophan and brain disordersSchizophrenia research and treatmentAmino Acid Enzymes and Metabolism

Kynurenine pathway in psychosis: evidence of increased tryptophan degradation

Barry, S, Clarke, G, Scully, P, Dinan, TG·2009·Journal of Psychopharmacology

Abstract

The kynurenine pathway of tryptophan degradation may serve to integrate disparate abnormalities heretofore identified in research aiming to elucidate the complex aetiopathogenesis of psychotic disorders. Post-mortem brain tissue studies have reported elevated kynurenine and kynurenic acid in the frontal cortex and upregulation of the first step of the pathway in the anterior cingulate cortex of individuals with schizophrenia. In this study, we examined kynurenine pathway activity by measuring tryptophan breakdown, a number of pathway metabolites and interferon gamma (IFN-gamma), which is the preferential activator of the first-step enzyme, indoleamine dioxygenase (IDO), in the plasma of patients with major psychotic disorder. Plasma tryptophan, kynurenine pathway metabolites were measured using high-performance liquid chromatography (HPLC) in 34 patients with a diagnosis on the psychotic spectrum (schizophrenia or schizoaffective disorder) and in 36 healthy control subjects. IFN-gamma was measured using enzyme-linked immunosorbent assay (ELISA). The mean tryptophan breakdown index (kynurenine/tryptophan) was significantly higher in the patient group compared with controls (P < 0.05). IFN-gamma measures did not differ between groups (P = 0.23). No relationship was found between measures of psychopathology, symptom severity and activity in the first step in the pathway. A modest correlation was established between the tryptophan breakdown index and illness duration. These results provide evidence for kynurenine pathway upregulation, specifically involving the first enzymatic step, in patients with major psychotic disorder. Increased tryptophan degradation in psychoses may have potential consequences for the treatment of these disorders by informing the development of novel therapeutic compounds.

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Crossref · 10.1177/0269881108089583

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  • Dysregulation of the kynurenine pathway has been linked to several brain disorders, including depression, schizophrenia, and autism spectrum disorder.

    “Dysregulation of the kynurenine pathway has been linked to several brain disorders, including depression (395), schizophrenia (396, 397), and ASD (398).”

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Authors
Barry, S., Clarke, G., Scully, P., & Dinan, T.
Affiliations
  • University College Cork (IE)
  • Department of Psychiatry, The Alimentary Pharmabiotic Center, University College Cork, Cork, Ireland
Corresponding author
Barry, S
Venue
Journal of Psychopharmacology
Published
2008-06-18
Volume
23
Issue
3
Pages
287-294
ISSN
  • 0269-8811 (ISSN-L)
  • 1461-7285
OpenAlex
W2010473895
Cited by
96
References
53
Citations by year
2026: 1 · 2025: 2 · 2024: 4 · 2023: 5 · 2022: 6 · 2021: 10 · 2020: 9 · 2019: 5 · 2018: 8 · 2017: 10 · 2016: 4 · 2014: 2 · 2013: 5 · 2012: 3
FWCI
2.45
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Psychopharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • Lenus, The Irish Health Repository (Dr Steevens Hospital Library) (submittedVersion)
Funders
  • Eli Lilly and Company
  • Wellcome Trust
  • Science Foundation Ireland
Topics
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Keywords
kynurenine pathway, tryptophan degradation, psychosis, schizophrenia, schizoaffective disorder, indoleamine 2,3-dioxygenase, interferon-gamma, kynurenine, kynurenic acid, plasma tryptophan, disease duration, aetiology of psychosis
MeSH terms
Adult, Chromatography, High Pressure Liquid, Enzyme-Linked Immunosorbent Assay, Female, Humans, Interferon-gamma, Kynurenine, Male, Middle Aged, Psychotic Disorders, Schizophrenia, Severity of Illness Index, Tryptophan, Up-Regulation, Indoleamine-Pyrrole 2,3,-Dioxygenase

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