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000884807 1001_ $$0P:(DE-HGF)0$$aJabbi, Mbemba$$b0$$eCorresponding author
000884807 245__ $$aNeuro-transcriptomic signatures for mood disorder morbidity and suicide mortality
000884807 260__ $$aAmsterdam [u.a.]$$bElsevier Science$$c2020
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000884807 520__ $$aSuicidal behaviors are strongly linked with mood disorders, but the specific neurobiological and functional gene-expression correlates for this linkage remain elusive. We performed neuroimaging-guided RNA-sequencing in two studies to test the hypothesis that imaging-localized gray matter volume (GMV) loss in mood disorders, harbors gene-expression changes associated with disease morbidity and related suicide mortality in an independent postmortem cohort. To do so, first, we conducted study 1 using an anatomical likelihood estimation (ALE) MRI meta-analysis including a total of 47 voxel-based morphometry (VBM) publications (i.e. 26 control versus (vs) major depressive disorder (MDD) studies, and 21 control vs bipolar disorder (BD) studies) in 2387 (living) participants. Study 1 meta-analysis identified a selective anterior insula cortex (AIC) GMV loss in mood disorders. We then used this results to guide study 2 postmortem tissue dissection and RNA-Sequencing of 100 independent donor brain samples with a life-time history of MDD (N = 30), BD (N = 37) and control (N = 33). In study 2, exploratory factor-analysis identified a higher-order factor representing number of Axis-1 diagnoses (e.g. substance use disorders/psychosis/anxiety, etc.), referred to here as morbidity and suicide-completion referred to as mortality. Comparisons of case-vs-control, and factor-analysis defined higher-order-factor contrast variables revealed that the imaging-identified AIC GMV loss sub-region harbors differential gene-expression changes in high morbidity-&-mortality versus low morbidity-&-mortality cohorts in immune, inflammasome, and neurodevelopmental pathways. Weighted gene co-expression network analysis further identified co-activated gene modules for psychiatric morbidity and mortality outcomes. These results provide evidence that AIC anatomical signature for mood disorders are possible correlates for gene-expression abnormalities in mood morbidity and suicide mortality.
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000884807 7001_ $$0P:(DE-HGF)0$$aArasappan, Dhivya$$b1
000884807 7001_ $$0P:(DE-Juel1)131678$$aEickhoff, Simon B.$$b2
000884807 7001_ $$0P:(DE-HGF)0$$aStrakowski, Stephen M.$$b3
000884807 7001_ $$0P:(DE-HGF)0$$aNemeroff, Charles B.$$b4
000884807 7001_ $$0P:(DE-HGF)0$$aHofmann, Hans A.$$b5
000884807 773__ $$0PERI:(DE-600)1500641-4$$a10.1016/j.jpsychires.2020.05.013$$gVol. 127, p. 62 - 74$$p62 - 74$$tJournal of psychiatric research$$v127$$x0022-3956$$y2020
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