%0 Journal Article
%A Jabbi, Mbemba
%A Arasappan, Dhivya
%A Eickhoff, Simon B.
%A Strakowski, Stephen M.
%A Nemeroff, Charles B.
%A Hofmann, Hans A.
%T Neuro-transcriptomic signatures for mood disorder morbidity and suicide mortality
%J Journal of psychiatric research
%V 127
%@ 0022-3956
%C Amsterdam [u.a.]
%I Elsevier Science
%M FZJ-2020-03265
%P 62 - 74
%D 2020
%X Suicidal 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:32485434
%U <Go to ISI:>//WOS:000539441300009
%R 10.1016/j.jpsychires.2020.05.013
%U https://juser.fz-juelich.de/record/884807