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 Research & Giving News Article  Blood Test For Mood Disorders Experiment is a “Proof of Principle,” But Clinical Applications Are Far Off Alexander B. Niculescu III, M.D., Ph.D., assistant professor at the Indiana University School of Medicine and a 2002 and 2005 NARSAD Young Investigator, is lead author of a Feb. 26 report in the journal Molecular Psychiatry indicating that the biomarkers are present in differing amounts in individuals suffering from high or low mood states. The blood concentration of the markers is postulated to vary depending on the severity of the depression or mania that an individual experiences. For an abstract of the team’s paper, go to: http://www.nature.com/mp/journal/vaop/ncurrent/abs/mp200811a.html “This discovery is a major step towards bringing psychiatry on par with other medical specialties that have diagnostic tools to measure disease states and the effectiveness of treatments,” Dr. Niculescu said. “Although psychiatrists have been aware that bipolar illness and other psychiatric conditions produced molecular changes in the brain, there was no way to measure those changes while the patient was living. But blood now can be used to diagnose and assess the severity of the illness.” Clinical Applications Are Not Imminent Dr. Niculescu’s biomarkers are not ready for use in the clinic. Rather, their identification is a proof of principle, intended to demonstrate the feasibility of developing such biomarkers for clinical use. Indeed, any correlation between a patient's psychiatric condition and expression of particular genes -- which is the basis of Dr. Niculescu’s biomarkers -- could potentially provide doctors with insight into the development of disease. However, a full understanding of how the proteins manufactured by these genes impact behavior is still a long way off, and so too, therefore, are clinical applications. Dr. Niculescu’s team measured the expression, or activity, of genes across the human genome from blood samples drawn from 96 patients with bipolar disorder, dividing them in groups that had “low mood” and “high mood” at the time of the test. These gene expression results were then correlated with results from tests involving strains of experimental mice genetically altered to model bipolar illness, and with other gene-expression data previously developed in other labs. Using a method they call “convergent functional genomics,” Dr. Niculescu’s team then “cross-validated and prioritized” their findings. Figuring Out What the Gene Data Signifies This method left them with a list of genes expressed in the patients’ blood samples which the team believes to be correlated with “high” and “low” mood states. These include five genes involved in the sheathing of nerve fibers, a process called myelination (Mbp, Edg2, Mag, Pmp22 and Ugt8), and six genes involved in growth factor signaling (Fgfr1, Fzd3, Erbb3, Igfbp4, Igfbp6 and Ptprm). All of these genes have prior evidence of being expressed differently in people with mood disorders relative to people without mood disorders, based on analysis of brain tissue taken from human subjects following death. Taken together, the list of genes yielded a “predictive score,” based on 10 top candidate biomarkers (five for “high” mood and five for “low” mood). That score, said the researchers, “shows sensitivity and specificity for high mood and low mood states, in two independent cohorts. Our studies suggest that blood biomarkers may offer an unexpectedly informative window into brain functioning and disease state.” According to Indiana University, “the researchers are planning a larger study looking at these mood markers in response to treatments, and they will use their unique methodology to seek biomarkers for other psychiatric diseases.” |
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