Kynurenine pathway in psychosis: evidence of increased tryptophan degradation.

Hdl Handle:
http://hdl.handle.net/10147/302735
Title:
Kynurenine pathway in psychosis: evidence of increased tryptophan degradation.
Authors:
Barry, Sandra; Clarke, G; Scully, P; Dinan, T G
Affiliation:
Department of Psychiatry, The Alimentary Pharmabiotic Center, University College Cork, Cork, Ireland. sandra.barry@mailp.hse.ie
Citation:
Kynurenine pathway in psychosis: evidence of increased tryptophan degradation. 2009, 23 (3):287-94 J. Psychopharmacol. (Oxford)
Publisher:
Journal of psychopharmacology (Oxford, England)
Journal:
Journal of psychopharmacology (Oxford, England)
Issue Date:
May-2009
URI:
http://hdl.handle.net/10147/302735
DOI:
10.1177/0269881108089583
PubMed ID:
18562404
Additional Links:
http://www.ncbi.nlm.nih.gov/pubmed/18562404
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.
Item Type:
Article
Language:
en
Description:
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.
Keywords:
MENTAL AND BEHAVIOURAL DISORDER; CHEMICAL
Local subject classification:
NEUROPSYCHIATRY
MeSH:
Adult; Chromatography, High Pressure Liquid; Enzyme-Linked Immunosorbent Assay; Female; Humans; Indoleamine-Pyrrole 2,3,-Dioxygenase; Interferon-gamma; Kynurenine; Male; Middle Aged; Psychotic Disorders; Schizophrenia; Severity of Illness Index; Tryptophan; Up-Regulation
ISSN:
0269-8811

Full metadata record

DC FieldValue Language
dc.contributor.authorBarry, Sandraen_GB
dc.contributor.authorClarke, Gen_GB
dc.contributor.authorScully, Pen_GB
dc.contributor.authorDinan, T Gen_GB
dc.date.accessioned2013-10-04T15:43:17Z-
dc.date.available2013-10-04T15:43:17Z-
dc.date.issued2009-05-
dc.identifier.citationKynurenine pathway in psychosis: evidence of increased tryptophan degradation. 2009, 23 (3):287-94 J. Psychopharmacol. (Oxford)en_GB
dc.identifier.issn0269-8811-
dc.identifier.pmid18562404-
dc.identifier.doi10.1177/0269881108089583-
dc.identifier.urihttp://hdl.handle.net/10147/302735-
dc.descriptionThe 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.en_GB
dc.description.abstractThe 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.-
dc.language.isoenen
dc.publisherJournal of psychopharmacology (Oxford, England)en_GB
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed/18562404en_GB
dc.rightsArchived with thanks to Journal of psychopharmacology (Oxford, England)en_GB
dc.subjectMENTAL AND BEHAVIOURAL DISORDERen_GB
dc.subjectCHEMICALen_GB
dc.subject.meshAdult-
dc.subject.meshChromatography, High Pressure Liquid-
dc.subject.meshEnzyme-Linked Immunosorbent Assay-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshIndoleamine-Pyrrole 2,3,-Dioxygenase-
dc.subject.meshInterferon-gamma-
dc.subject.meshKynurenine-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshPsychotic Disorders-
dc.subject.meshSchizophrenia-
dc.subject.meshSeverity of Illness Index-
dc.subject.meshTryptophan-
dc.subject.meshUp-Regulation-
dc.subject.otherNEUROPSYCHIATRYen_GB
dc.titleKynurenine pathway in psychosis: evidence of increased tryptophan degradation.en_GB
dc.typeArticleen
dc.contributor.departmentDepartment of Psychiatry, The Alimentary Pharmabiotic Center, University College Cork, Cork, Ireland. sandra.barry@mailp.hse.ieen_GB
dc.identifier.journalJournal of psychopharmacology (Oxford, England)en_GB

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