Targeted and Non-Targeted Metabolomic Evaluation of Cerebrospinal Fluid in Early Phase Schizophrenia: A Pilot Study from the Hopkins First Episode Psychosis Project
(1) Background: The lack of reliable biomarkers remains a significant barrier to improving outcomes for patients with schizophrenia. While metabolomic analyses of blood, urine, and feces have been explored, results have been inconsistent. Compared to peripheral compartments, cerebrospinal fluid (CSF...
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| author | George E. Jaskiw Mark E. Obrenovich Curtis J. Donskey Farren B. S. Briggs Sun Sunnie Chung Anastasiya I. Kalinina Austin Bolomey Lindsay N. Hayes Kun Yang Robert H. Yolken Akira Sawa |
| author_facet | George E. Jaskiw Mark E. Obrenovich Curtis J. Donskey Farren B. S. Briggs Sun Sunnie Chung Anastasiya I. Kalinina Austin Bolomey Lindsay N. Hayes Kun Yang Robert H. Yolken Akira Sawa |
| author_sort | George E. Jaskiw |
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| description | (1) Background: The lack of reliable biomarkers remains a significant barrier to improving outcomes for patients with schizophrenia. While metabolomic analyses of blood, urine, and feces have been explored, results have been inconsistent. Compared to peripheral compartments, cerebrospinal fluid (CSF) more closely reflects the chemical composition of brain extracellular fluid. Given that brain dysregulation may be more pronounced during the first episode of psychosis (FEP), we hypothesized that metabolomic analysis of CSF from FEP patients could reveal disease-associated biomarkers. (2) Methods: We recruited 15 patients within 24 months of psychosis onset (DSM-4 criteria) and 14 control participants through the Johns Hopkins Schizophrenia Center. CSF samples were analyzed using both non-targeted and targeted liquid chromatography–mass spectrometry. (3) Results: The non-targeted analysis identified lower levels of N-acetylneuraminic acid and N-acetyl-L-aspartic acid in the FEP group, while levels of uric acid were elevated. The targeted analysis focused on indolic and phenolic molecules previously linked to neuropsychiatric disorders. Notably, L-phenylalanine and 4-hydroxycinnamic acid levels were lower in the FEP group, and this difference remained significant after adjusting for age and sex. However, none of the significant differences in analyte levels between the groups survived an adjustment for multiple comparisons. (4) Conclusions: Our intriguing but preliminary associations align with results from other investigational approaches and highlight potential CSF analytes that warrant further study in larger samples. |
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| issn | 2218-1989 |
| language | English |
| publishDate | 2025-04-01 |
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| series | Metabolites |
| spelling | doaj-art-3477bc2feb2b4da3bf8ea3ca443ad2d92025-08-20T02:28:24ZengMDPI AGMetabolites2218-19892025-04-0115427510.3390/metabo15040275Targeted and Non-Targeted Metabolomic Evaluation of Cerebrospinal Fluid in Early Phase Schizophrenia: A Pilot Study from the Hopkins First Episode Psychosis ProjectGeorge E. Jaskiw0Mark E. Obrenovich1Curtis J. Donskey2Farren B. S. Briggs3Sun Sunnie Chung4Anastasiya I. Kalinina5Austin Bolomey6Lindsay N. Hayes7Kun Yang8Robert H. Yolken9Akira Sawa10Veterans Affairs Northeast Ohio Healthcare System, Cleveland, OH 44106, USAVeterans Affairs Northeast Ohio Healthcare System, Cleveland, OH 44106, USAVeterans Affairs Northeast Ohio Healthcare System, Cleveland, OH 44106, USADepartment Public Health Sciences, Miller School of Medicine, University of Miami, Miami, FL 33136, USADepartment of Computer Science, Cleveland State University, Cleveland, OH 44115, USADepartment of Computer Science, Cleveland State University, Cleveland, OH 44115, USAVeterans Affairs Northeast Ohio Healthcare System, Cleveland, OH 44106, USADepartment of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USAStanley Division of Developmental Neurovirology, Johns Hopkins School of Medicine, The Johns Hopkins Hospital, Baltimore, MD 21287, USADepartments of Psychiatry, Neuroscience, Biomedical Engineering, Pharmacology, Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA(1) Background: The lack of reliable biomarkers remains a significant barrier to improving outcomes for patients with schizophrenia. While metabolomic analyses of blood, urine, and feces have been explored, results have been inconsistent. Compared to peripheral compartments, cerebrospinal fluid (CSF) more closely reflects the chemical composition of brain extracellular fluid. Given that brain dysregulation may be more pronounced during the first episode of psychosis (FEP), we hypothesized that metabolomic analysis of CSF from FEP patients could reveal disease-associated biomarkers. (2) Methods: We recruited 15 patients within 24 months of psychosis onset (DSM-4 criteria) and 14 control participants through the Johns Hopkins Schizophrenia Center. CSF samples were analyzed using both non-targeted and targeted liquid chromatography–mass spectrometry. (3) Results: The non-targeted analysis identified lower levels of N-acetylneuraminic acid and N-acetyl-L-aspartic acid in the FEP group, while levels of uric acid were elevated. The targeted analysis focused on indolic and phenolic molecules previously linked to neuropsychiatric disorders. Notably, L-phenylalanine and 4-hydroxycinnamic acid levels were lower in the FEP group, and this difference remained significant after adjusting for age and sex. However, none of the significant differences in analyte levels between the groups survived an adjustment for multiple comparisons. (4) Conclusions: Our intriguing but preliminary associations align with results from other investigational approaches and highlight potential CSF analytes that warrant further study in larger samples.https://www.mdpi.com/2218-1989/15/4/275metabolomecerebrospinal fluidfirst-episode psychosisschizophreniabiomarkergut microbiome |
| spellingShingle | George E. Jaskiw Mark E. Obrenovich Curtis J. Donskey Farren B. S. Briggs Sun Sunnie Chung Anastasiya I. Kalinina Austin Bolomey Lindsay N. Hayes Kun Yang Robert H. Yolken Akira Sawa Targeted and Non-Targeted Metabolomic Evaluation of Cerebrospinal Fluid in Early Phase Schizophrenia: A Pilot Study from the Hopkins First Episode Psychosis Project Metabolites metabolome cerebrospinal fluid first-episode psychosis schizophrenia biomarker gut microbiome |
| title | Targeted and Non-Targeted Metabolomic Evaluation of Cerebrospinal Fluid in Early Phase Schizophrenia: A Pilot Study from the Hopkins First Episode Psychosis Project |
| title_full | Targeted and Non-Targeted Metabolomic Evaluation of Cerebrospinal Fluid in Early Phase Schizophrenia: A Pilot Study from the Hopkins First Episode Psychosis Project |
| title_fullStr | Targeted and Non-Targeted Metabolomic Evaluation of Cerebrospinal Fluid in Early Phase Schizophrenia: A Pilot Study from the Hopkins First Episode Psychosis Project |
| title_full_unstemmed | Targeted and Non-Targeted Metabolomic Evaluation of Cerebrospinal Fluid in Early Phase Schizophrenia: A Pilot Study from the Hopkins First Episode Psychosis Project |
| title_short | Targeted and Non-Targeted Metabolomic Evaluation of Cerebrospinal Fluid in Early Phase Schizophrenia: A Pilot Study from the Hopkins First Episode Psychosis Project |
| title_sort | targeted and non targeted metabolomic evaluation of cerebrospinal fluid in early phase schizophrenia a pilot study from the hopkins first episode psychosis project |
| topic | metabolome cerebrospinal fluid first-episode psychosis schizophrenia biomarker gut microbiome |
| url | https://www.mdpi.com/2218-1989/15/4/275 |
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