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The kynurenine pathway in schizophrenia, bipolar disorder, and major depressive disorder: a systematic review and meta-analysis of cerebrospinal fluid studies
- E. Salagre, B. S. Fernandes, M. E. Inam, I. Grande, E. Vieta, J. Quevedo, Z. Zhao
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S620
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Introduction
The kynurenine pathway has been suggested to be involved in the pathophysiology of psychiatric disorders, including schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD).
ObjectivesTo conduct a systematic review and meta-analysis of the kynurenine pathway metabolites from cerebrospinal fluid samples in SZ, BD, and MDD.
MethodsPubMed and Scopus databases were searched from inception to April 2022 to identify case-control studies assessing kynurenine metabolites [tryptophan (TRP), kynurenine (KYN), kynurenic acid (KA), quinolinic acid (QA), and 3-hydroxykynurenine (3-HK)] in SZ, BD, and MDD vs. healthy controls (HC). PRISMA guidelines were followed in the literature review. The random effects model parameter was selected when comparing the standardized mean differences (SMD) between groups.
ResultsA total of 23 articles met inclusion criteria (number of articles k=8, 8, 11 for SZ, BD, and MDD, respectively). For SZ, KA levels were increased in SZ compared to HC (SMD=2.64, CI=1.16-4.13, p=0.0005, I2=96%, k=6, n=384). KYN levels were not significantly different between SZ and HC (SMD=4.19, CI=-0.70 to 9.09, p=0.0933, I2=99%, k=4, n=188). For BD, TRP levels (k=7) did not differ significantly between BD and HC. There was a limited number of studies to conclude increased levels of KA in BD (k=2). For MDD, although some studies tended toward increased levels of KYN in those with remission vs. decreased levels in those with current depression, there were no significant differences in any of the kynurenine metabolite levels. There was a limited number of studies to conclude increased levels of QA in MDD (k=2).
ConclusionsKA, which has possibly neuroprotective effects, is increased in SZ. QA, which has neurotoxic effects, may be increased in MDD. There may be alterations in this pathway based on population characteristics and mood states.
Disclosure of InterestE. Salagre: None Declared, B. Fernandes: None Declared, M. Inam: None Declared, I. Grande Grant / Research support from: Spanish Ministry of Science and Innovation (MCIN) (PI19/00954) integrated into the Plan Nacional de I+D+I and cofinanced by the ISCIII-Subdireccion General de Evaluacion y el Fondos Europeos de la Unión Europea (FEDER, FSE, Next Generation EU/Plan de Recuperación Transformación y Resiliencia_PRTR); the Instituto de Salud Carlos III; the CIBER of Mental Health (CIBERSAM); and the Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement (2017 SGR 1365), CERCA Programme / Generalitat de Catalunya as well as the Fundació Clínic per la Recerca Biomèdica (Pons Bartran 2022-FRCB_PB1_2022), Paid Instructor of: ADAMED, Angelini, Casen Recordati, Ferrer, Janssen Cilag, and Lundbeck, Lundbeck-Otsuka, Luye, SEI Healthcare , E. Vieta Grant / Research support from: Spanish Ministry of Science and Innovation (PI15/00283, PI18/00805) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER); the Instituto de Salud Carlos III; the CIBER of Mental Health (CIBERSAM); the Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement (2017 SGR 1365), the CERCA Programme, and the Departament de Salut de la Generalitat de Catalunya for the PERIS grant SLT006/17/00357, Paid Instructor of: AB-Biotics, AbbVie, Angelini, Biogen, Boehringer-Ingelheim, Celon Pharma, Dainippon Sumitomo Pharma, Ferrer, Gedeon Richter, GH Research, Glaxo-Smith Kline, Janssen, Lundbeck, Novartis, Orion Corporation, Organon, Otsuka, Sage, Sanofi-Aventis, Sunovion, and Takeda, J. Quevedo: None Declared, Z. Zhao: None Declared
The effectiveness of involuntary electroconvulsive therapy (ECT): A population-based study
- E. Salagre, C. Rohde, K. Ishtiak-Ahmed, C. Gasse, S. Østergaard
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- Journal:
- European Psychiatry / Volume 64 / Issue S1 / April 2021
- Published online by Cambridge University Press:
- 13 August 2021, pp. S151-S152
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Introduction
Involuntary electroconvulsive therapy (ECT) can be a life-saving intervention for patients suffering from potentially lethal conditions who are unable to give informed consent. However, its use is not widespread, probably partly due to the scarce data on hard outcomes following involuntary ECT. In Denmark, involuntary ECT is only used when patients are at imminent/potential risk of dying if not receiving ECT.
ObjectivesWe aimed to assess the effectiveness of involuntary ECT by estimating the 1-year survival following its administration.
MethodsWe conducted a register-based cohort study involving i) all patients receiving involuntary ECT in Denmark between 2008 and 2019, ii) age and sex-matched patients receiving voluntary ECT, and iii) age and sex-matched individuals from the general population. 1-year survival rates were compared via mortality rate ratios.
ResultsWe identified 618 patients receiving involuntary ECT, 547 patients receiving voluntary ECT, and 3,080 population-based controls. The survival rate in the year after involuntary ECT was 90%. For patients receiving involuntary ECT, the 1-year mortality rate ratios were 3.1 (95% confidence interval (CI)= 1.9-5.2) and 5.8 (95%CI = 4.0-8.2) compared to those receiving voluntarily ECT and to the population-based controls, respectively. Risk factors for early death among patients receiving involuntary ECT were male sex, being ≥70 years old and having organic mental disorder as the treatment indication.
ConclusionsTreatment with involuntary ECT is associated with a high survival rate, suggesting that the intervention is effective. However, patients receiving involuntary ECT constitute a high-risk population that should be monitored closely after this treatment.
DisclosureNo significant relationships.
Homocysteine as a peripheral biomarker in bipolar disorder: A meta-analysis
- E. Salagre, A.F. Vizuete, M. Leite, D.J. Brownstein, A. McGuinness, F. Jacka, S. Dodd, B. Stubbs, C.A. Köhler, E. Vieta, A.F. Carvalho, M. Berk, B.S. Fernandes
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- Journal:
- European Psychiatry / Volume 43 / June 2017
- Published online by Cambridge University Press:
- 23 March 2020, pp. 81-91
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Background:
Bipolar disorder (BD) is a psychiatric disorder with an uncertain aetiology. Recently, special attention has been given to homocysteine (Hcy), as it has been suggested that alterations in 1-carbon metabolism might be implicated in diverse psychiatric disorders. However, there is uncertainty regarding possible alterations in peripheral Hcy levels in BD.
Methods:This study comprises a meta-analysis comparing serum and plasma Hcy levels in persons with BD and healthy controls. We conducted a systematic search for all eligible English and non-English peer-reviewed articles.
Results:Nine cross-sectional studies were included in the meta-analyses, providing data on 1547 participants. Random-effects meta-analysis showed that serum and plasma levels of Hcy were increased in subjects with BD in either mania or euthymia when compared to healthy controls, with a large effect size in the mania group (g = 0.98, 95% CI: 0.8–1.17, P < 0.001, n = 495) and a small effect in the euthymia group (g = 0.3, 95% CI: 0.11–0.48, P = 0.002, n = 1052).
Conclusions:Our meta-analysis provides evidence that Hcy levels are elevated in persons with BD during mania and euthymia. Peripheral Hcy could be considered as a potential biomarker in BD, both of trait (since it is increased in euthymia), and also of state (since its increase is more accentuated in mania). Longitudinal studies are needed to clarify the relationship between bipolar disorder and Hcy, as well as the usefulness of peripheral Hcy as both a trait and state biomarker in BD.