Metabolic profiling of CSF: Evidence that early intervention may impact on disease progression and outcome in schizophrenia

Elaine Holmes, Tsz M. Tsang, Jeffrey T.J. Huang, F. Markus Leweke, Dagmar Koethe, Christoph W. Gerth, Brit M. Nolden, Sonja Gross, Daniela Schreiber, Jeremy K. Nicholson, Sabine Bahn

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    Abstract

    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: 1H 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. Copyright:

    Original languageEnglish
    Pages (from-to)1420-1428
    Number of pages9
    JournalPLoS Medicine
    Volume3
    Issue number8
    DOIs
    Publication statusPublished - 22 Aug 2006

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