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Huang JT, Leweke FM, Oxley D, Wang L, Harris N, Koethe D, Gerth CW, Nolden BM, Gross S, Schreiber D, Reed B, Bahn S. Disease biomarkers in cerebrospinal fluid of patients with first-onset psychosis. PLoS Med. 2006 Nov 1 ; 3(11):e428. Pubmed Abstract

Comments on News and Primary Papers
Comment by:  Stephen J. Glatt
Submitted 4 December 2006
Posted 4 December 2006
  I recommend the Primary Papers

This paper by Huang, Bahn, and colleagues makes for very interesting reading and provides an early glimpse into the future of proteomic studies of schizophrenia and other mental disorders. Although some interesting new leads have been provided regarding particular proteins and peptides, these will need replication, as the authors themselves acknowledge. Thus, we should not get caught up in those details at this time, but rather appreciate this work for its greater contribution, which is in the modern theoretical framework that drives the study.

First and foremost, it is refreshing to see a focus on a syndrome, such as psychosis, rather than traditional focus on DSM-based diagnostic boundaries. This approach is one that our group has also endorsed in recent years in light of overlapping linkage, association, and gene expression data in schizophrenia and bipolar disorder. It just makes sense that biomarkers will work best for symptoms or other lower-level traits or states rather than hierarchical diagnoses with questionable validity. In turn, biomarker work performed in this manner may subsequently inform the derivation of novel, biologically based, valid diagnostic categories.

The use of CSF samples is laudatory, since this provides a good balance between access to the central nervous system and ease of sample collection, whereas other modern biomarker studies of blood or postmortem brain tissue do not allow for such balance. The protein-chip technology itself is also impressive, although as with any cutting-edge technology in its infancy, major improvements in resolution and throughput will be needed to move this technique into the mainstream.

In summary, this manuscript should be read carefully by all those among us who are interested in the frontiers of biomarker research on mental disorders. However, in contrast to the authors' statement that "An alternative approach to genetic studies is to screen for disease markers (biomarkers)," we might be wise to treat biomarker research as a useful adjunct to—rather than replacement for—analyses of genetic polymorphisms.

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