TY - JOUR
T1 - Systems biology dissection of PTSD and MDD across brain regions, cell types, and blood
AU - PTSD Working Group of Psychiatric Genomics Consortium
AU - Daskalakis, Nikolaos P.
AU - Iatrou, Artemis
AU - Chatzinakos, Chris
AU - Jajoo, Aarti
AU - Snijders, Clara
AU - Wylie, Dennis
AU - DiPietro, Christopher P.
AU - Tsatsani, Ioulia
AU - Chen, Chia Yen
AU - Pernia, Cameron D.
AU - Soliva-Estruch, Marina
AU - Arasappan, Dhivya
AU - Bharadwaj, Rahul A.
AU - Collado-Torres, Leonardo
AU - Wuchty, Stefan
AU - Alvarez, Victor E.
AU - Dammer, Eric B.
AU - Deep-Soboslay, Amy
AU - Duong, Duc M.
AU - Eagles, Nick
AU - Huber, Bertrand R.
AU - Huuki, Louise
AU - Holstein, Vincent L.
AU - Logue, Mark W.
AU - Lugenbühl, Justina F.
AU - Maihofer, Adam X.
AU - Miller, Mark W.
AU - Nievergelt, Caroline M.
AU - Pertea, Geo
AU - Ross, Deanna
AU - Sendi, Mohammad S.E.
AU - Sun, Benjamin B.
AU - Tao, Ran
AU - Tooke, James
AU - Wolf, Erika J.
AU - Zeier, Zane
AU - Berretta, Sabina
AU - Champagne, Frances A.
AU - Hyde, Thomas
AU - Seyfried, Nicholas T.
AU - Shin, Joo Heon
AU - Weinberger, Daniel R.
AU - Nemeroff, Charles B.
AU - Kleinman, Joel E.
AU - Ressler, Kerry J.
N1 - Publisher Copyright: © 2024 the authors, some rights reserved.
PY - 2024/5/24
Y1 - 2024/5/24
N2 - The molecular pathology of stress-related disorders remains elusive. Our brain multiregion, multiomic study of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) included the central nucleus of the amygdala, hippocampal dentate gyrus, and medial prefrontal cortex (mPFC). Genes and exons within the mPFC carried most disease signals replicated across two independent cohorts. Pathways pointed to immune function, neuronal and synaptic regulation, and stress hormones. Multiomic factor and gene network analyses provided the underlying genomic structure. Single nucleus RNA sequencing in dorsolateral PFC revealed dysregulated (stress-related) signals in neuronal and non-neuronal cell types. Analyses of brain-blood intersections in >50,000 UK Biobank participants were conducted along with fine-mapping of the results of PTSD and MDD genome-wide association studies to distinguish risk from disease processes. Our data suggest shared and distinct molecular pathology in both disorders and propose potential therapeutic targets and biomarkers.
AB - The molecular pathology of stress-related disorders remains elusive. Our brain multiregion, multiomic study of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) included the central nucleus of the amygdala, hippocampal dentate gyrus, and medial prefrontal cortex (mPFC). Genes and exons within the mPFC carried most disease signals replicated across two independent cohorts. Pathways pointed to immune function, neuronal and synaptic regulation, and stress hormones. Multiomic factor and gene network analyses provided the underlying genomic structure. Single nucleus RNA sequencing in dorsolateral PFC revealed dysregulated (stress-related) signals in neuronal and non-neuronal cell types. Analyses of brain-blood intersections in >50,000 UK Biobank participants were conducted along with fine-mapping of the results of PTSD and MDD genome-wide association studies to distinguish risk from disease processes. Our data suggest shared and distinct molecular pathology in both disorders and propose potential therapeutic targets and biomarkers.
UR - https://www.scopus.com/pages/publications/85194126108
U2 - 10.1126/science.adh3707
DO - 10.1126/science.adh3707
M3 - Article
C2 - 38781393
SN - 0036-8075
VL - 384
JO - Science
JF - Science
IS - 6698
M1 - eadh3707
ER -