bio sphere
Schizophrenia leaves its signature in the blood Females with schizophrenia have distinct metabolic patterns.
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Thus, the female twins with large VLDL by projection to latent structure disy analyzing the NMR spectra of criminant analysis (PL S-DA). “PL S-DA and LDL shifts also exhibited altered plasma, scientists have boosted the behavior. “This is to our knowledge the maximizes the covariance in the NMR evidence that abnormal metabolism first observation that we can actually redata with disease class,” Holmes says. contributes to schizophrenia. Sabine late a biomarker with the functioning of “The method also has an internal crossBahn, Elaine Holmes, and colleagues the patient,” Bahn says. validation, which helps protect against at the University of Cambridge and Many scientists attribute abnormal overfitting data.” Imperial College London (both in the metabolism in schizophrenia U.K.) found that the NMR to antipsychotic drugs, signals from a number of though such abnormalities lipids and proteins differenhad been reported even betiated female twins with 10 fore the era of drug treatschizophrenia from unafment. The researchers argue fected co-twins (J. Proteome 0 that use of antipsychotic Res. 2006, 5, 756–760). In drugs is unlikely to account statistical analyses, the unaffor their results. “We found fected co-twins fell between –10 a similar signature very the affected twins and conprominently in the nontrol twins. “Therefore, 10 20 schizophrenic female coschizophrenic twins can be Sample ID twins,” Bahn says. “And the separated from their unafmales with schizophrenia, fected twins based on a who had similar or even multiple metabolite signaPLS-DA scores derived from NMR data differentiated among female cohigher doses of antipsyture in blood plasma,” says twins with schizophrenia (red dots), unaffected co-twins (blue dots), chotics, didn’t show that Holmes. and control twins (black squares). correlation.” Wong says, The researchers analyzed “This study design is especially imporWhen PL S-DA scores were plotted ~60 metabolites simultaneously in plastant because antipsychotic medications against sample number, the affected ma collected by Fuller Torrey at the have a major impact on weight and metwins clustered to the right of the plot, Stanley Medical Research Institute. The tabolism, and it is hard to exclude medthe unaffected co-twins clustered in the 58 samples came from 21 pairs of disication effects. So the finding that the middle, and the control twins clustered cordant twins (in which only one twin unaffected co-twin also has abnormal to the left. This separation was especialhad schizophrenia) and 16 pairs of profiles, similar to the affected twin but ly pronounced when only the data for matched control twins. According to to a lesser degree, is quite compelling.” Albert Wong at the University of Toron- the female twins were plotted. The Karoly Mirnics at the University of groupings disappeared when only the to, “The use of NMR spectroscopy on Pittsburgh says that VLDL and LDL male data were used. Bahn points out sera is novel, as are the comparisons beshifts, together with many other periphthat schizophrenia develops later in fetween discordant twins and unaffected eral assays, might one day become part males. Moreover, females have a better twins.” of an objective biomarker test that prognosis. Estrogen is thought to be Compared with plasma from the uncould be performed easily during risk protective and is known to influence affected co-twins, plasma from the afLDL and VLDL levels. “It will be of in- screening, clinical diagnosis, evaluation fected co-twins produced stronger resoterest to further explore the relationship of therapy, and the development of new nances in the regions representing very antipsychotic drugs. “For this to hapbetween estrogen and lipid metabolism low density lipoproteins (VLDLs) and pen,” he says, “the predictive value of in the pathophysiology of schizophrelow-density lipoproteins (LDLs) and these and other observations must be weaker resonances in the baseline region nia,” she says. tested on new, expanded cohorts. This Remarkably, the NMR shifts relating (probably from underlying proteins). To and other similar studies are pivotal in to VLDL and LDL correlated negativedetermine whether those spectral differdefining in which directions we should ly with the female twins’ Global Funcences could distinguish among the afproceed.” a tioning scores, which assess how well fected, unaffected, and control groups, —Linda Sage people cope with everyday situations. the researchers analyzed the NMR data © 2006 AMERICAN CHEMICAL SOCIETY
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