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Metabolic Profiling of CSF: Evidence That Early Intervention May Impact on Disease Progression and Outcome in Schizophrenia

BACKGROUND: The identification of schizophrenia biomarkers is a crucial step towards improving current diagnosis, developing new presymptomatic treatments, identifying high-risk individuals and disease subgroups, and assessing the efficacy of preventative interventions at a rate that is not currentl...

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Autores principales: Holmes, Elaine, Tsang, Tsz M, Huang, Jeffrey T.-J, Leweke, F. Markus, Koethe, Dagmar, Gerth, Christoph W, Nolden, Brit M, Gross, Sonja, Schreiber, Daniela, Nicholson, Jeremy K, Bahn, Sabine
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1551919/
https://www.ncbi.nlm.nih.gov/pubmed/16933966
http://dx.doi.org/10.1371/journal.pmed.0030327
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author Holmes, Elaine
Tsang, Tsz M
Huang, Jeffrey T.-J
Leweke, F. Markus
Koethe, Dagmar
Gerth, Christoph W
Nolden, Brit M
Gross, Sonja
Schreiber, Daniela
Nicholson, Jeremy K
Bahn, Sabine
author_facet Holmes, Elaine
Tsang, Tsz M
Huang, Jeffrey T.-J
Leweke, F. Markus
Koethe, Dagmar
Gerth, Christoph W
Nolden, Brit M
Gross, Sonja
Schreiber, Daniela
Nicholson, Jeremy K
Bahn, Sabine
author_sort Holmes, Elaine
collection PubMed
description BACKGROUND: The identification of schizophrenia biomarkers is a crucial step towards improving current diagnosis, developing new presymptomatic treatments, identifying high-risk individuals and disease subgroups, and assessing the efficacy of preventative interventions at a rate that is not currently possible. METHODS AND FINDINGS: (1)H nuclear magnetic resonance spectroscopy in conjunction with computerized pattern recognition analysis were employed to investigate metabolic profiles of a total of 152 cerebrospinal fluid (CSF) samples from drug-naïve or minimally treated patients with first-onset paranoid schizophrenia (referred to as “schizophrenia” in the following text) and healthy controls. Partial least square discriminant analysis showed a highly significant separation of patients with first-onset schizophrenia away from healthy controls. Short-term treatment with antipsychotic medication resulted in a normalization of the disease signature in over half the patients, well before overt clinical improvement. No normalization was observed in patients in which treatment had not been initiated at first presentation, providing the first molecular evidence for the importance of early intervention for psychotic disorders. Furthermore, the alterations identified in drug-naïve patients could be validated in a test sample set achieving a sensitivity and specificity of 82% and 85%, respectively. CONCLUSIONS: Our findings suggest brain-specific alterations in glucoregulatory processes in the CSF of drug-naïve patients with first-onset schizophrenia, implying that these abnormalities are intrinsic to the disease, rather than a side effect of antipsychotic medication. Short-term treatment with atypical antipsychotic medication resulted in a normalization of the CSF disease signature in half the patients well before a clinical improvement would be expected. Furthermore, our results suggest that the initiation of antipsychotic treatment during a first psychotic episode may influence treatment response and/or outcome.
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spelling pubmed-15519192006-09-18 Metabolic Profiling of CSF: Evidence That Early Intervention May Impact on Disease Progression and Outcome in Schizophrenia Holmes, Elaine Tsang, Tsz M Huang, Jeffrey T.-J Leweke, F. Markus Koethe, Dagmar Gerth, Christoph W Nolden, Brit M Gross, Sonja Schreiber, Daniela Nicholson, Jeremy K Bahn, Sabine PLoS Med Research Article BACKGROUND: The identification of schizophrenia biomarkers is a crucial step towards improving current diagnosis, developing new presymptomatic treatments, identifying high-risk individuals and disease subgroups, and assessing the efficacy of preventative interventions at a rate that is not currently possible. METHODS AND FINDINGS: (1)H nuclear magnetic resonance spectroscopy in conjunction with computerized pattern recognition analysis were employed to investigate metabolic profiles of a total of 152 cerebrospinal fluid (CSF) samples from drug-naïve or minimally treated patients with first-onset paranoid schizophrenia (referred to as “schizophrenia” in the following text) and healthy controls. Partial least square discriminant analysis showed a highly significant separation of patients with first-onset schizophrenia away from healthy controls. Short-term treatment with antipsychotic medication resulted in a normalization of the disease signature in over half the patients, well before overt clinical improvement. No normalization was observed in patients in which treatment had not been initiated at first presentation, providing the first molecular evidence for the importance of early intervention for psychotic disorders. Furthermore, the alterations identified in drug-naïve patients could be validated in a test sample set achieving a sensitivity and specificity of 82% and 85%, respectively. CONCLUSIONS: Our findings suggest brain-specific alterations in glucoregulatory processes in the CSF of drug-naïve patients with first-onset schizophrenia, implying that these abnormalities are intrinsic to the disease, rather than a side effect of antipsychotic medication. Short-term treatment with atypical antipsychotic medication resulted in a normalization of the CSF disease signature in half the patients well before a clinical improvement would be expected. Furthermore, our results suggest that the initiation of antipsychotic treatment during a first psychotic episode may influence treatment response and/or outcome. Public Library of Science 2006-08 2006-08-22 /pmc/articles/PMC1551919/ /pubmed/16933966 http://dx.doi.org/10.1371/journal.pmed.0030327 Text en © 2006 Holmes et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Holmes, Elaine
Tsang, Tsz M
Huang, Jeffrey T.-J
Leweke, F. Markus
Koethe, Dagmar
Gerth, Christoph W
Nolden, Brit M
Gross, Sonja
Schreiber, Daniela
Nicholson, Jeremy K
Bahn, Sabine
Metabolic Profiling of CSF: Evidence That Early Intervention May Impact on Disease Progression and Outcome in Schizophrenia
title Metabolic Profiling of CSF: Evidence That Early Intervention May Impact on Disease Progression and Outcome in Schizophrenia
title_full Metabolic Profiling of CSF: Evidence That Early Intervention May Impact on Disease Progression and Outcome in Schizophrenia
title_fullStr Metabolic Profiling of CSF: Evidence That Early Intervention May Impact on Disease Progression and Outcome in Schizophrenia
title_full_unstemmed Metabolic Profiling of CSF: Evidence That Early Intervention May Impact on Disease Progression and Outcome in Schizophrenia
title_short Metabolic Profiling of CSF: Evidence That Early Intervention May Impact on Disease Progression and Outcome in Schizophrenia
title_sort metabolic profiling of csf: evidence that early intervention may impact on disease progression and outcome in schizophrenia
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1551919/
https://www.ncbi.nlm.nih.gov/pubmed/16933966
http://dx.doi.org/10.1371/journal.pmed.0030327
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