Altered Gene Synchrony Suggests a Combined Hormone-Mediated Dysregulated State in Major Depression 英文参考文献.docVIP

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Altered Gene Synchrony Suggests a Combined Hormone-Mediated Dysregulated State in Major Depression 英文参考文献.doc

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Altered Gene Synchrony Suggests a Combined Hormone-Mediated Dysregulated State in Major Depression 英文参考文献

AlteredGeneSynchronySuggestsaCombined Hormone-MediatedDysregulatedStateinMajor Depression ChrisGaiteri1,2,Jean-PhilippeGuilloux1,3,DavidA.Lewis1,2,EtienneSibille1,2 * 1DepartmentofPsychiatry,UniversityofPittsburgh,Pittsburgh,Pennsylvania,UnitedStatesofAmerica,2CenterforNeuroscience,UniversityofPittsburgh,Pittsburgh, Pennsylvania,UnitedStatesofAmerica,3Faculte′ dePharmacie,Universite′ Paris-SudEA3544,Cha?tenay-Malabry, France Abstract Coordinated gene transcript levels across tissues (denoted ‘‘gene synchrony’’) reflect converging influences of genetic, biochemicalandenvironmentalfactors;hencetheyareinformativeofthebiologicalstateofanindividual.Socouldbrain gene synchrony also integrate the multiple factors engaged in neuropsychiatric disorders and reveal underlying pathologies?UsingbootstrappedPearsoncorrelationfortranscriptlevelsforthesamegenesacrossdistinctbrainareas,we reportrobustgenetranscriptsynchronybetweentheamygdalaandcingulatecortexinthehumanpostmortembrainof normal control subjects (n=14; Control/Permutated data, p,0.000001). Coordinated expression was confirmed across distinctprefrontalcortexareasinaseparatecohort(n=19subjects)andaffecteddifferentgenesets,potentiallyreflecting regional network- and function-dependent transcriptional programs. Genewise regional transcript coordination was independentofage-relatedchangesandarraytechnicalparameters.Robustshiftsinamygdala-cingulategenesynchrony were observed in subjects with major depressive disorder (MDD, denoted here ‘‘depression’’) (n=14; MDD/Permutated data,p,0.000001),significantlyaffectingbetween100and250individualgenes(10–30%falsediscoveryrate).Biological networks and signal transduction pathways corresponding to the identified gene set suggested putative dysregulated functions for several hormone-type factors previously implicated in depression (insulin, interleukin-1, thyroid hormone, estradiol and glucocorticoids; p,0.01 for association with depression-related networks). In summary, we show