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@ARTICLE{Jabbi:884807,
author = {Jabbi, Mbemba and Arasappan, Dhivya and Eickhoff, Simon B.
and Strakowski, Stephen M. and Nemeroff, Charles B. and
Hofmann, Hans A.},
title = {{N}euro-transcriptomic signatures for mood disorder
morbidity and suicide mortality},
journal = {Journal of psychiatric research},
volume = {127},
issn = {0022-3956},
address = {Amsterdam [u.a.]},
publisher = {Elsevier Science},
reportid = {FZJ-2020-03265},
pages = {62 - 74},
year = {2020},
abstract = {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.},
cin = {INM-7},
ddc = {610},
cid = {I:(DE-Juel1)INM-7-20090406},
pnm = {571 - Connectivity and Activity (POF3-571)},
pid = {G:(DE-HGF)POF3-571},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:32485434},
UT = {WOS:000539441300009},
doi = {10.1016/j.jpsychires.2020.05.013},
url = {https://juser.fz-juelich.de/record/884807},
}