Metabolic profiling of CSF: evidence that early intervention may impact on disease progression and outcome in schizophrenia.
Metabolic profiling of CSF: evidence that early intervention may impact on disease progression and outcome in schizophrenia.
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DOI：
10.1371/journal.pmed.0030327
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发表时间：
2006-08
期刊：
影响因子：
15.8
通讯作者：
Bahn, Sabine
中科院分区：
文献类型：
--
作者：
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
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. 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. 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. Metabolic profiling of the cerebrospinal fluid shows differences between healthy controls and patients with first-onset schizophrenia. Early treatment appears to rapidly normalize the profiles in some of the patients. Biological markers, or “biomarkers,” are combinations of molecules that are present in certain diseases. Scientists are interested in discovering new biomarkers because they could be useful for diagnosis of those diseases. The presence of such biomarkers might in some cases even precede the development of disease symptoms, which could help in early diagnosis, treatment, and maybe even prevention. Schizophrenia is a disease for which no “objective” biological test exists, and scientists are trying to find biomarkers that would help with diagnosis. The current diagnosis of schizophrenia is based on the symptoms experienced and reported by the patient, in combination with signs observed by a psychiatrist, clinical psychologist, or other clinician. This study was done to search for biomarkers for schizophrenia. The researchers studied the metabolic state of patients and healthy volunteers (controls). In other words, they focused on the small molecules present in cells, tissues, or body fluids. The metabolic state reflects what has been encoded by a person's genes and modified by environmental factors. Focusing on the metabolic state makes sense for a disease like schizophrenia, since many different genetic and environmental factors are thought to be responsible for causing it. The researchers studied the metabolic state of 82 patients with schizophrenia and 70 healthy controls by studying the levels of different molecules present in their cerebrospinal fluid (the clear body fluid that surrounds the brain and the spinal cord). Of the patients, 54 had just been diagnosed with schizophrenia (or a similar illness called brief psychotic disorder) and had not yet taken any medications to treat schizophrenia (so-called antipsychotic medication). The remaining patients were undergoing treatment with a range of antipsychotic drugs. The researchers found different levels of certain molecules in the spinal fluid of newly diagnosed patients who had never taken schizophrenia drugs compared with healthy individuals of the same ages. These molecules might therefore turn out to be useful biomarkers for schizophrenia. The differences between patients and controls suggested that the metabolism of several substances—including glucose and acetate—might be altered in the brains of patients with schizophrenia or brief psychotic disorder. The researchers also found that the levels of these molecules in some of the patients with newly diagnosed schizophrenia who were given medication became similar to the levels in the control individuals. These results are encouraging because they suggest that studying “metabolic profiles” might lead to finding a set of biomarkers that could reliably help in early diagnosis of schizophrenia. Such biomarkers might possibly also help in monitoring patients' responses to drug treatment. However, as acknowledged by the study's authors and emphasized by Rima Kaddhurah Daouk in an accompanying Perspective, these early results need to be tested in larger studies and confirmed before their clinical relevance will be known. It will be important for such follow-up studies to involve patients with other psychiatric diseases (not just schizophrenia), to see whether the biomarkers are specific to schizophrenia or whether they indicate a broader range of psychiatric diseases. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030327. National Institutes of Mental Health pages on schizophrenia The National Alliance for Research on Schizophrenia and Depression The National Alliance for the Mentally Ill The Schizophrenia Society of Canada Wikipedia page on schizophrenia (note: Wikipedia is an online encyclopedia that anyone can edit)
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影响因子：
--
作者：
HAWKINS, RA;MANS, AM;DAVIS, DW
通讯作者：
DAVIS, DW
影响因子：
10.6
作者：
Karry, R;Klein, E;Ben Shachar, D
通讯作者：
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DOI：
10.1016/s1385-299x(98)00033-6
发表时间：
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期刊：
BRAIN RESEARCH PROTOCOLS
影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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San, L