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News Brief—Metabolites in Blood and Urine: Future Laboratory Test for Schizophrenia?

11 November 2011. A laboratory test to diagnose schizophrenia has long been near the top of the clinical wish list, but to date, no widely accepted biomarkers have been identified (see SRF related news story). A report published online October 25 in Molecular Psychiatry pushes a new candidate into the ring: Researchers led by Chunling Wan and Wei Jia of Shanghai Jiao Tong University, China, performed a global metabolic profiling study of biomarkers in schizophrenia and, using a combined serum and urine metabolite panel, was able to distinguish schizophrenia subjects from controls with a high degree of accuracy.

By dividing the subject cohort (comprising 112 schizophrenia subjects and 110 healthy controls) into a training set and a test set, first authors Jinglei Yang and Tianlu Chen identified a panel of serum biomarkers that differed between the two diagnostic groups. Those that made the cut: glycerate, eicosenoic acid, β-hydroxybutyrate, pyruvate, and cysteine. The addition of urine β-hydroxybutyrate increased the accuracy of the panel, and resulted in a correct diagnosis for every subject. Importantly, approximately 60 percent of the schizophrenia subjects were first-episode patients who had never received antipsychotics, and the remainder had been off medication for at least four weeks, suggesting that the metabolite changes are unlikely to be due to an effect of neuroleptics.

In addition, Yang, Chen, and colleagues report increased levels of multiple fatty acids and ketone bodies in schizophrenia, which may reflect an upregulation of fatty acid catabolism that the authors attribute to deficient brain glucose supply.—Allison A. Curley.

Yang J, Chen T, Sun L, Zhao Z, Qi X, Zhou K, Cao Y, Wang X, Qiu Y, Su M, Zhao A, Wang P, Yang P, Wu J, Feng G, He L, Jia W, Wan C. Potential metabolite markers of schizophrenia. Mol Psychiatry. 2011 Oct 25. Abstract

Comments on News and Primary Papers
Primary Papers: Potential metabolite markers of schizophrenia.

Comment by:  Michael O'Donovan, SRF Advisor
Submitted 1 November 2011 Posted 2 November 2011
  I recommend this paper

The authors suggest they have developed a biomarker test for schizophrenia based upon a handful of serum measures and one urine metabolite. The properties are said to be equivalent to a diagnostic interview. However, caution is required, and the history suggests so is a healthy dose of skepticism. But if the findings of a perfect test, or even a remotely near-perfect test, are confirmed, and particularly if they apply to very early disease, this will prove to be a landmark paper. Confirmatory studies are essential, which is why I have recommended this paper.

View all comments by Michael O'Donovan

Primary Papers: Potential metabolite markers of schizophrenia.

Comment by:  Sabine BahnPaul C. Guest
Submitted 14 November 2011 Posted 14 November 2011

The development of biomarkers and the implications of using these to improve diagnostics and clinical trials are becoming more apparent, even for cases of psychiatric disorders such as schizophrenia. The regulatory health authorities now consider biomarkers as important in the pharmaceutical industry, and the Food and Drug Administration (FDA) has called for modernization and standardization of methods, tools, and techniques for the purpose of delivering better and safer drugs (Owens, 2006; Marson, 2007). The FDA has stipulated that molecules must achieve the status of validated biomarkers before they can be used in the regulatory process for clinical trials. This means that biomarkers should be measured in a test system with strict performance characteristics, that there is an established scientific proof of concept to explain the results, and that the test can be replicated with similar results in different laboratories and at different sites.

In the latest Issue of Molecular Psychiatry, Yang and coworkers describe the...  Read more

View all comments by Sabine Bahn
View all comments by Paul C. Guest

Comment by:  Stephen J. Glatt
Submitted 22 November 2011 Posted 23 November 2011
  I recommend the Primary Papers

This line of work is immensely important, as the lack of reliable biomarkers presents a major barrier to the receipt of a definitive diagnosis and the initiation of treatment; ultimately, the detection of biomarkers that are present at first episode may also signal biomarkers that may be present in the prodrome and even before symptoms emerge, which might provide a basis for earlier intervention and prevention. As elegantly summarized by Drs. Bahn, Guest, and O'Donovan, these results will need replication in diverse samples before they can be capitalized upon in the form of a clinically useful test; however, it does make sense that a biomarker profile derived from multiple sources (serum and urine) might have better explanatory power than a profile derived from just one source. Similarly, the next frontier in the development of biomarker panels may involve what I've called a polyomic approach, taking into account genetic and functional genomic variation as well as metabolite variability as demonstrated here.

View all comments by Stephen J. Glatt

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