A Metabolomics Study of Serum in Hospitalized Patients With Chronic Schizophrenia
Purpose: Metabolomics has attracted attention as a new method for understanding the molecular mechanisms of psychiatric disorders. Current metabolomics technology allows us to measure over hundreds of metabolites at a time and is a useful indicator of the consequences of complex and continuous chang...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-12-01
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| Series: | Frontiers in Psychiatry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fpsyt.2021.763547/full |
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| author | Naomichi Okamoto Naomichi Okamoto Atsuko Ikenouchi Atsuko Ikenouchi Keita Watanabe Ryohei Igata Rintaro Fujii Reiji Yoshimura |
| author_facet | Naomichi Okamoto Naomichi Okamoto Atsuko Ikenouchi Atsuko Ikenouchi Keita Watanabe Ryohei Igata Rintaro Fujii Reiji Yoshimura |
| author_sort | Naomichi Okamoto |
| collection | DOAJ |
| description | Purpose: Metabolomics has attracted attention as a new method for understanding the molecular mechanisms of psychiatric disorders. Current metabolomics technology allows us to measure over hundreds of metabolites at a time and is a useful indicator of the consequences of complex and continuous changes in metabolic profiles due to the execution of genomic information and external factors of biological activity. Therefore, metabolomics is imperative to the discovery of biomarkers and mechanisms associated with pathophysiological processes. In this study, we investigated metabolites changes in hospitalized patients with chronic schizophrenia compared to that in healthy controls, and examined the correlations between the metabolites and psychiatric symptoms.Patients and Methods: Thirty patients with schizophrenia and ten healthy controls participated in this study between September 2019 and June 2020. The mean duration of disease in patients with schizophrenia was 26 years. Clinical and neuropsychiatric symptoms of patients with schizophrenia were assessed using the Positive and Negative Syndrome Scale (PANSS). Metabolomics was conducted using Capillary Electrophoresis Fourier Transform Mass Spectrometry (CE-FTMS), using serum samples from patients with schizophrenia and healthy controls. Metabolomics assigned a candidate compound to the 446 (cation 279, anion 167) peaks. Hierarchical cluster analysis (HCA), principal component analysis (PCA), logistic regression analysis, receiver operating characteristic (ROC) analysis, and linear regression analysis were used to analyze the metabolites changes, identifying the disease and the relationship between metabolites and psychiatric symptoms.Results: HCA showed that approximately 60% of metabolites had lower peak values in patients with schizophrenia than in healthy controls. Glutamate metabolism and the urea cycle had the highest proportions in the metabolic pathway, which decreased in patients with schizophrenia. PCA showed a clear separation between patients with schizophrenia and healthy controls in the first principal component (the contribution ratio of the first principal component was 15.9%). Logistic regression analysis suggested that the first principal component was a predictor of disease (odds = 1.36, 95%CI = 1.11–1.67, p = 0.0032). ROC analysis showed a sensitivity of 93% and a specificity of 100% for the diagnosis of schizophrenia with a cut-off value of the first principal component; −3.33 (AUC = 0.95). We extracted the high factor loading for the first principal component. Gamma-glutamyl-valine (γ-Glu-Val) was significantly negatively correlated with PANSS total scores (r = −0.45, p = 0.012) and PANSS general scores (r = −0.49, p = 0.0055). Gamma-glutamyl-phenylalanine (γ-Glu-Phe) was significantly negatively correlated with PANSS total score (r = −0.40, p = 0.031) and PANSS general score (r = −0.41, p = 0.025). Tetrahydrouridine was significantly positively correlated with PANSS negative scores (r = 0.53, p = 0.0061).Conclusion: Metabolites changes in hospitalized patients with chronic schizophrenia showed extensive and generalized declines. Glutamate metabolism and the urea cycle had the highest proportions in the metabolic pathway, which decreased in the schizophrenia group. Metabolomic analysis was useful to identify chronic schizophrenia. Some glutamate compound metabolites had a relationship with psychiatric symptoms. |
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| id | doaj.art-aec902dcd6cb4738a33954cff80a20d2 |
| institution | Directory Open Access Journal |
| issn | 1664-0640 |
| language | English |
| last_indexed | 2024-12-24T11:02:54Z |
| publishDate | 2021-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Psychiatry |
| spelling | doaj.art-aec902dcd6cb4738a33954cff80a20d22022-12-21T16:58:40ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402021-12-011210.3389/fpsyt.2021.763547763547A Metabolomics Study of Serum in Hospitalized Patients With Chronic SchizophreniaNaomichi Okamoto0Naomichi Okamoto1Atsuko Ikenouchi2Atsuko Ikenouchi3Keita Watanabe4Ryohei Igata5Rintaro Fujii6Reiji Yoshimura7Medical Center for Dementia, University Hospital, University of Occupational and Environmental Health, Kitakyushu, JapanDepartment of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, JapanMedical Center for Dementia, University Hospital, University of Occupational and Environmental Health, Kitakyushu, JapanDepartment of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, JapanOpen Innovation Laboratory, Kyoto University, Kyoto, JapanDepartment of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, JapanDepartment of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, JapanDepartment of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, JapanPurpose: Metabolomics has attracted attention as a new method for understanding the molecular mechanisms of psychiatric disorders. Current metabolomics technology allows us to measure over hundreds of metabolites at a time and is a useful indicator of the consequences of complex and continuous changes in metabolic profiles due to the execution of genomic information and external factors of biological activity. Therefore, metabolomics is imperative to the discovery of biomarkers and mechanisms associated with pathophysiological processes. In this study, we investigated metabolites changes in hospitalized patients with chronic schizophrenia compared to that in healthy controls, and examined the correlations between the metabolites and psychiatric symptoms.Patients and Methods: Thirty patients with schizophrenia and ten healthy controls participated in this study between September 2019 and June 2020. The mean duration of disease in patients with schizophrenia was 26 years. Clinical and neuropsychiatric symptoms of patients with schizophrenia were assessed using the Positive and Negative Syndrome Scale (PANSS). Metabolomics was conducted using Capillary Electrophoresis Fourier Transform Mass Spectrometry (CE-FTMS), using serum samples from patients with schizophrenia and healthy controls. Metabolomics assigned a candidate compound to the 446 (cation 279, anion 167) peaks. Hierarchical cluster analysis (HCA), principal component analysis (PCA), logistic regression analysis, receiver operating characteristic (ROC) analysis, and linear regression analysis were used to analyze the metabolites changes, identifying the disease and the relationship between metabolites and psychiatric symptoms.Results: HCA showed that approximately 60% of metabolites had lower peak values in patients with schizophrenia than in healthy controls. Glutamate metabolism and the urea cycle had the highest proportions in the metabolic pathway, which decreased in patients with schizophrenia. PCA showed a clear separation between patients with schizophrenia and healthy controls in the first principal component (the contribution ratio of the first principal component was 15.9%). Logistic regression analysis suggested that the first principal component was a predictor of disease (odds = 1.36, 95%CI = 1.11–1.67, p = 0.0032). ROC analysis showed a sensitivity of 93% and a specificity of 100% for the diagnosis of schizophrenia with a cut-off value of the first principal component; −3.33 (AUC = 0.95). We extracted the high factor loading for the first principal component. Gamma-glutamyl-valine (γ-Glu-Val) was significantly negatively correlated with PANSS total scores (r = −0.45, p = 0.012) and PANSS general scores (r = −0.49, p = 0.0055). Gamma-glutamyl-phenylalanine (γ-Glu-Phe) was significantly negatively correlated with PANSS total score (r = −0.40, p = 0.031) and PANSS general score (r = −0.41, p = 0.025). Tetrahydrouridine was significantly positively correlated with PANSS negative scores (r = 0.53, p = 0.0061).Conclusion: Metabolites changes in hospitalized patients with chronic schizophrenia showed extensive and generalized declines. Glutamate metabolism and the urea cycle had the highest proportions in the metabolic pathway, which decreased in the schizophrenia group. Metabolomic analysis was useful to identify chronic schizophrenia. Some glutamate compound metabolites had a relationship with psychiatric symptoms.https://www.frontiersin.org/articles/10.3389/fpsyt.2021.763547/fullschizophreniametabolomicsmetabolomeglutamatetetrahydrouridine |
| spellingShingle | Naomichi Okamoto Naomichi Okamoto Atsuko Ikenouchi Atsuko Ikenouchi Keita Watanabe Ryohei Igata Rintaro Fujii Reiji Yoshimura A Metabolomics Study of Serum in Hospitalized Patients With Chronic Schizophrenia Frontiers in Psychiatry schizophrenia metabolomics metabolome glutamate tetrahydrouridine |
| title | A Metabolomics Study of Serum in Hospitalized Patients With Chronic Schizophrenia |
| title_full | A Metabolomics Study of Serum in Hospitalized Patients With Chronic Schizophrenia |
| title_fullStr | A Metabolomics Study of Serum in Hospitalized Patients With Chronic Schizophrenia |
| title_full_unstemmed | A Metabolomics Study of Serum in Hospitalized Patients With Chronic Schizophrenia |
| title_short | A Metabolomics Study of Serum in Hospitalized Patients With Chronic Schizophrenia |
| title_sort | metabolomics study of serum in hospitalized patients with chronic schizophrenia |
| topic | schizophrenia metabolomics metabolome glutamate tetrahydrouridine |
| url | https://www.frontiersin.org/articles/10.3389/fpsyt.2021.763547/full |
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