Using a convergent functional genomics approach that incorporates avariety of experimental techniques, the scientists also were ableto apply a panel of their top genes to data from other studies ofschizophrenia and successfully identify which patients had beendiagnosed with schizophrenia and which had not, according to areport recently published online by the journal Molecular Psychiatry. Evaluating the biological pathways in which the genes are active,the researchers also proposed a model of schizophrenia as a diseaseemerging from a mix of genetic variations affecting braindevelopment and neuronal connections along with environmentalfactors, particularly stress. "At its core, schizophrenia is a disease of decreased cellularconnectivity in the brain, precipitated by environmental stressduring brain development, among those with geneticvulnerability," said principal investigator Alexander B.Niculescu III, M.D., Ph.D., associate professor of psychiatry andmedical neuroscience at the IU School of Medicine and director ofthe Laboratory of Neurophenomics at the Institute of PsychiatricResearch at the IU School of Medicine. "For first time we have a comprehensive list of the genes thathave the best evidence for involvement in schizophrenia," saidNiculescu, who is also staff psychiatrist and investigator at theRichard L.
Roudebush Veterans Affairs Medical Center. Schizophrenia is a relatively widespread psychiatric disease,affecting about 1 percent of the population, often with devastatingimpact. People with schizophrenia can have difficulty thinkinglogically and telling the difference between real and unrealexperiences, and may engage in bizarre behavior. When the test estimating the risk for schizophrenia is refined, itcould provide guidance to caregivers and health care professionalsabout young people in families with a history of the disease,prompting early intervention and treatment when behavioral symptomsof schizophrenia occurred among those at higher risk, Dr.
Niculescusaid. He stressed that a score indicating a higher risk of schizophrenia"doesn't determine your destiny. It just means that yourneuronal connectivity is different, which could make you morecreative, or more prone to illness." "It's all on a continuum; these genetic variants are presentthroughout the population. If you have too many of them, in thewrong combination, in an environment where you are exposed tostress, alcohol and drugs, and so on, that can lead to thedevelopment of the clinical illness," he said. The prototype test was able to predict whether a person was at ahigher or lower risk of schizophrenia in about two-thirds of cases.
To identify and prioritize the genes, the researchers combined datafrom several different types of studies. These included genome-wideassociation studies, gene expression data derived from human tissuesamples, genetic linkage studies, genetic evidence from animalmodels, and other work. This approach, called convergent functionalgenomics, has been pioneered by Niculescu and colleagues, andrelies on multiple independent lines of evidence to implicate genesin clinical disorders. The authors noted that the results were stronger when analyses wereperformed using gene-level data, rather than analyses based onindividual mutations -- called single nucleotide polymorphisms, orSNPs -- in those genes.
Multiple different SNPs can spark aparticular gene's role in the development of schizophrenia, soevidence for the genes, and the biological mechanisms in which theyplay a role, was much stronger from study to study than was theevidence for individual SNPs. Past research looking at individual mutations was difficult toreplicate from study to study, Dr. Niculescu said. The new paper,however, indicates that much of the research done in recent yearshas in fact produced consistent results at a gene and biologicalpathway level.
"There is a lot more reproducibility and concordance in thefield than people realized," he said. "Finally now, by better understanding the genetic andbiological basis of the illness, we can develop better tests forit, as well as better treatments. The future of medicine is notjust treatment but prevention, so we hope this work will movethings in the right direction." Additional authors of the paper are Mikias Ayalew, HelenLe-Niculescu, Daniel Levey, Nitika Jain, Bharathi Eddula-Changala,Sagar Patel, Evan Winiger, Alan Breier, Anantha Shekhar, JohnNurnberger, and Daniel Koller from IU; Aiden Corvin from TrinityCollege; Mark Geyer and Ming Tsuang from UC San Diego; DanielSalomon and Nicholas Schork from The Scripps Research Institute;Richard Amdur and Ayman Fanous from Washington DC VA MedicalCenter; and Michael O' Donovan from Cardiff University. Support for the research was provided by a National Institutes ofHealth Director's New Innovator Award (1DP2OD007363) and a VeteransAdministration Merit Award (1I01CX000139-01). I am Home Supplies writer, reports some information about fine arts lamps , britax baby safe.
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