The kynurenine pathway in major depressive disorder, bipolar disorder, and schizophrenia: a meta-analysis of 101 studies

被引：208

作者：

Marx, Wolfgang ^{[1
]}

McGuinness, Amelia J. ^{[1
]}

Rocks, Tetyana ^{[1
]}

Ruusunen, Anu ^{[1
,2
,3
]}

Cleminson, Jasmine ^{[1
]}

Walker, Adam J. ^{[1
]}

Gomes-da-Costa, Susana ^{[4
]}

Lane, Melissa ^{[1
]}

Sanches, Marsal ^{[5
,6
]}

Diaz, Alexandre P. ^{[5
,6
]}

Tseng, Ping-Tao ^{[7
,8
]}

Lin, Pao-Yen ^{[9
,10
,11
]}

Berk, Michael ^{[1
]}

Clarke, Gerard ^{[12
,13
]}

O'Neil, Adrienne ^{[1
]}

Jacka, Felice ^{[1
]}

Stubbs, Brendon ^{[14
,15
]}

Carvalho, Andre F. ^{[16
,17
]}

Quevedo, Joao ^{[5
]}

Soares, Jair C. ^{[5
]}

Fernandes, Brisa S. ^{[5
,6
]}

机构：

[1] Deakin Univ, IMPACT Inst Mental & Phys Hlth & Clin Translat, Sch Med, Barwon Hlth, Geelong, Vic, Australia

[2] Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland

[3] Kuopio Univ Hosp, Dept Psychiat, Kuopio, Finland

[4] Univ Barcelona, Bipolar & Depress Disorders Unit, Inst Neurosci, Hosp Clin,IDIBAPS,CIBERSAM, Barcelona, Catalonia, Spain

[5] Univ Texas Hlth Sci Ctr Houston UTHlth, McGovern Med Sch, Faillace Dept Psychiat & Behav Sci, Ctr Excellence Mood Disorders, Houston, TX 77030 USA

[6] Univ Texas Hlth Sci Ctr Houston UTHlth, McGovern Med Sch, Faillace Dept Psychiat & Behav Sci, Translat Psychiat Program, Houston, TX 77030 USA

[7] Natl Sun Yat Sen Univ, Inst Biomed Sci, Kaohsiung, Taiwan

[8] Natl Sun Yat Sen Univ, Prospect Clin Otorhinolaryngol & Neurol, Kaohsiung, Taiwan

[9] Kaohsiung Chang Gung Mem Hosp, Dept Psychiat, Kaohsiung, Taiwan

[10] Chang Gung Univ, Coll Med, Kaohsiung, Taiwan

[11] Kaohsiung Chang Gung Mem Hosp, Inst Translat Res Biomed Sci, Kaohsiung, Taiwan

[12] Univ Coll Cork, Dept Psychiat & Neurobehav Sci, Cork, Ireland

[13] Univ Coll Cork, APC Microbiome Ireland, Cork, Ireland

[14] Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Psychol Med, London, England

[15] South London & Maudsley NHS Fdn Trust, London, England

[16] Univ Toronto, Dept Psychiat, Toronto, ON, Canada

[17] Ctr Addict & Mental Hlth, Toronto, ON, Canada

来源：

MOLECULAR PSYCHIATRY | 2021年 / 26卷 / 08期

基金：

英国医学研究理事会; 澳大利亚研究理事会; 澳大利亚国家健康与医学研究理事会; 爱尔兰科学基金会;

关键词：

DECREASED PLASMA TRYPTOPHAN; NEUTRAL AMINO-ACIDS; PLATELET SEROTONIN; DRUG-FREE; CEREBROSPINAL-FLUID; NEUROTROPHIC FACTOR; MEDICATION-NAIVE; SERUM TRYPTOPHAN; DOUBLE-BLIND; METABOLITES;

D O I：

10.1038/s41380-020-00951-9

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：4158 / 4178

页数：21

共 138 条

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