The kynurenine pathway in major depressive disorder, bipolar disorder, and schizophrenia: a systematic review and meta-analysis of cerebrospinal fluid studies
Objectives: The kynurenine (KYN) pathway has been attracting attention as a relevant pathway in schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). We conducted a systematic review and meta-analysis of studies examining KYN pathway metabolites from cerebrospinal fluid (C...
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| Format: | Article |
| Language: | English |
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Associação Brasileira de Psiquiatria (ABP)
2023-08-01
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| Series: | Brazilian Journal of Psychiatry |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-44462023005006201&lng=en&tlng=en |
| _version_ | 1797733719576936448 |
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| author | Mehmet Enes Inam Brisa S. Fernandes Estela Salagre Iria Grande Eduard Vieta João Quevedo Zhongming Zhao |
| author_facet | Mehmet Enes Inam Brisa S. Fernandes Estela Salagre Iria Grande Eduard Vieta João Quevedo Zhongming Zhao |
| author_sort | Mehmet Enes Inam |
| collection | DOAJ |
| description | Objectives: The kynurenine (KYN) pathway has been attracting attention as a relevant pathway in schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). We conducted a systematic review and meta-analysis of studies examining KYN pathway metabolites from cerebrospinal fluid (CSF) samples in SZ, BD, and MDD. Methods: The PubMed and Scopus databases were systematically searched to identify peer-reviewed case-control studies published until April 2022 that assessed KYN metabolites, namely, tryptophan (TRP), KYN, kynurenic acid (KA), quinolinic acid (QA), and 3-hydroxykynurenine (3-HK), in subjects with SZ, BD, or MDD compared with healthy controls (HC). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. The random effects model method was selected for comparison of standardized mean differences (SMD) between two groups. Results: Twenty-three articles met the inclusion criteria (k = 8, k = 8, k = 11, for SZ, BD, and MDD, respectively). In SZ, KA levels were increased (SMD = 2.64, confidence interval [CI] = 1.16 to 4.13, p = 0.0005, I2 = 96%, k = 6, n=384). TRP (k = 5) and KYN (k = 4) did not differ significantly. In BD, TRP levels (k = 7) did not differ significantly. The level of KA was increased in MDD (k = 2), but the small number of studies precluded evaluation of statistical significance. Finally, in MDD, although some studies tended to show an increased level of KYN in those with remission vs. decreased levels in those with current depression, no significant difference was found in any KYN metabolite levels. Similarly, an increased level of QA was found, but the number of studies (k = 2) was small. Conclusion: KA, which has possibly neuroprotective effects, is increased in SZ. QA, which has neurotoxic effects, may be increased in MDD. There were no alterations in BD. Alterations in the KYN pathway may occur based on population characteristics and mood states. Future studies should explore the utility of these metabolites as biomarkers. |
| first_indexed | 2024-03-12T12:32:14Z |
| format | Article |
| id | doaj.art-d2406fc9d1b84dd2a01faa2e1d94423e |
| institution | Directory Open Access Journal |
| issn | 1809-452X |
| language | English |
| last_indexed | 2024-03-12T12:32:14Z |
| publishDate | 2023-08-01 |
| publisher | Associação Brasileira de Psiquiatria (ABP) |
| record_format | Article |
| series | Brazilian Journal of Psychiatry |
| spelling | doaj.art-d2406fc9d1b84dd2a01faa2e1d94423e2023-08-29T07:48:00ZengAssociação Brasileira de Psiquiatria (ABP)Brazilian Journal of Psychiatry1809-452X2023-08-0110.47626/1516-4446-2022-2973The kynurenine pathway in major depressive disorder, bipolar disorder, and schizophrenia: a systematic review and meta-analysis of cerebrospinal fluid studiesMehmet Enes Inamhttps://orcid.org/0000-0002-6779-9377Brisa S. Fernandeshttps://orcid.org/0000-0002-3797-7582Estela SalagreIria Grandehttps://orcid.org/0000-0002-0137-0666Eduard Vietahttps://orcid.org/0000-0002-0548-0053João Quevedohttps://orcid.org/0000-0003-3114-6611Zhongming Zhaohttps://orcid.org/0000-0002-3477-0914 Objectives: The kynurenine (KYN) pathway has been attracting attention as a relevant pathway in schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). We conducted a systematic review and meta-analysis of studies examining KYN pathway metabolites from cerebrospinal fluid (CSF) samples in SZ, BD, and MDD. Methods: The PubMed and Scopus databases were systematically searched to identify peer-reviewed case-control studies published until April 2022 that assessed KYN metabolites, namely, tryptophan (TRP), KYN, kynurenic acid (KA), quinolinic acid (QA), and 3-hydroxykynurenine (3-HK), in subjects with SZ, BD, or MDD compared with healthy controls (HC). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. The random effects model method was selected for comparison of standardized mean differences (SMD) between two groups. Results: Twenty-three articles met the inclusion criteria (k = 8, k = 8, k = 11, for SZ, BD, and MDD, respectively). In SZ, KA levels were increased (SMD = 2.64, confidence interval [CI] = 1.16 to 4.13, p = 0.0005, I2 = 96%, k = 6, n=384). TRP (k = 5) and KYN (k = 4) did not differ significantly. In BD, TRP levels (k = 7) did not differ significantly. The level of KA was increased in MDD (k = 2), but the small number of studies precluded evaluation of statistical significance. Finally, in MDD, although some studies tended to show an increased level of KYN in those with remission vs. decreased levels in those with current depression, no significant difference was found in any KYN metabolite levels. Similarly, an increased level of QA was found, but the number of studies (k = 2) was small. Conclusion: KA, which has possibly neuroprotective effects, is increased in SZ. QA, which has neurotoxic effects, may be increased in MDD. There were no alterations in BD. Alterations in the KYN pathway may occur based on population characteristics and mood states. Future studies should explore the utility of these metabolites as biomarkers.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-44462023005006201&lng=en&tlng=enBiomarkerkynurenic acidquinolinic acidtryptophanmental disorders |
| spellingShingle | Mehmet Enes Inam Brisa S. Fernandes Estela Salagre Iria Grande Eduard Vieta João Quevedo Zhongming Zhao The kynurenine pathway in major depressive disorder, bipolar disorder, and schizophrenia: a systematic review and meta-analysis of cerebrospinal fluid studies Brazilian Journal of Psychiatry Biomarker kynurenic acid quinolinic acid tryptophan mental disorders |
| title | The kynurenine pathway in major depressive disorder, bipolar disorder, and schizophrenia: a systematic review and meta-analysis of cerebrospinal fluid studies |
| title_full | The kynurenine pathway in major depressive disorder, bipolar disorder, and schizophrenia: a systematic review and meta-analysis of cerebrospinal fluid studies |
| title_fullStr | The kynurenine pathway in major depressive disorder, bipolar disorder, and schizophrenia: a systematic review and meta-analysis of cerebrospinal fluid studies |
| title_full_unstemmed | The kynurenine pathway in major depressive disorder, bipolar disorder, and schizophrenia: a systematic review and meta-analysis of cerebrospinal fluid studies |
| title_short | The kynurenine pathway in major depressive disorder, bipolar disorder, and schizophrenia: a systematic review and meta-analysis of cerebrospinal fluid studies |
| title_sort | kynurenine pathway in major depressive disorder bipolar disorder and schizophrenia a systematic review and meta analysis of cerebrospinal fluid studies |
| topic | Biomarker kynurenic acid quinolinic acid tryptophan mental disorders |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-44462023005006201&lng=en&tlng=en |
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