期刊
MOLECULAR PSYCHIATRY
卷 26, 期 8, 页码 4158-4178出版社
SPRINGERNATURE
DOI: 10.1038/s41380-020-00951-9
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资金
- Alfred Deakin Postdoctoral Research Fellowship
- Multiple Sclerosis Research Australia
- Cancer Council Queensland
- La Trobe University
- Deakin University
- University of Queensland
- Bond University
- Cobram Estate Pty. Ltd.
- Nutrition Society of Australia
- Nutrition Research Australia
- Health Education England (HEE) [ICA-CL-2017-03-001]
- National Institute for Health Research (NIHR) [ICA-CL-2017-03-001]
- NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust
- Medical Research Council
- Guys and St Thomas Charity (GSTT)
- NHMRC [1059660, 1156072]
- Heart Foundation Australia [101160]
- Wilson Foundation
- National Health & Medical Research Council
- Australian Research Council
- University of Melbourne
- Sanofi
- Meat and Livestock Australia
- Woolworths Limited
- BeFit Foods
- Fundacion de Psiquiatria y Salud Mental
- Science Foundation Ireland (SFI), through the Irish Government's National Development Plan [SFI/12/RC/2273P2]
- Health Research Board (HRB) [ILP-POR-2017-013]
- Australian Rotary Health/Ten Island Tassie Tag Along Tour Funding Partner PhD Scholarship
- University of the Sunshine Coast
- Australian Postgraduate Awards
- Fernwood Foundation
- Be Fit Food
- Oxford University Press
- University of Sydney
- University of Southern Queensland
- Dietitians Association of Australia
- Royal Australian and New Zealand College of Psychiatrists
- Academy of Nutrition and Dietetics
- Black Dog Institute
- Australian Rotary Health
- Australian Disease Management Association
- Department of Health and Human Services
- Primary Health Networks
- Barwon Health
- West Gippsland Healthcare Group
- Central West Gippsland Primary Care Partnership
- Parkdale College
- Positive Schools
- City of Greater Geelong
- Global Age
- Health Research Board (HRB) [ILP-POR-2017-013] Funding Source: Health Research Board (HRB)
The study conducted a meta-analysis and found that tryptophan and kynurenine concentrations are reduced in patients with MDD, BD, and SZ, while kynurenic acid and the kynurenic acid to quinolinic acid ratio are decreased in mood disorders (i.e., MDD and BD).
The importance of tryptophan as a precursor for neuroactive compounds has long been acknowledged. The metabolism of tryptophan along the kynurenine pathway and its involvement in mental disorders is an emerging area in psychiatry. We performed a meta-analysis to examine the differences in kynurenine metabolites in major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ). Electronic databases were searched for studies that assessed metabolites involved in the kynurenine pathway (tryptophan, kynurenine, kynurenic acid, quinolinic acid, 3-hydroxykynurenine, and their associate ratios) in people with MDD, SZ, or BD, compared to controls. We computed the difference in metabolite concentrations between people with MDD, BD, or SZ, and controls, presented as Hedges' g with 95% confidence intervals. A total of 101 studies with 10,912 participants were included. Tryptophan and kynurenine are decreased across MDD, BD, and SZ; kynurenic acid and the kynurenic acid to quinolinic acid ratio are decreased in mood disorders (i.e., MDD and BD), whereas kynurenic acid is not altered in SZ; kynurenic acid to 3-hydroxykynurenine ratio is decreased in MDD but not SZ. Kynurenic acid to kynurenine ratio is decreased in MDD and SZ, and the kynurenine to tryptophan ratio is increased in MDD and SZ. Our results suggest that there is a shift in the tryptophan metabolism from serotonin to the kynurenine pathway, across these psychiatric disorders. In addition, a differential pattern exists between mood disorders and SZ, with a preferential metabolism of kynurenine to the potentially neurotoxic quinolinic acid instead of the neuroprotective kynurenic acid in mood disorders but not in SZ.
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