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Systems biology dissection of PTSD and MDD across brain regions, cell types, and blood.
Daskalakis, Nikolaos P; Iatrou, Artemis; Chatzinakos, Chris; Jajoo, Aarti; Snijders, Clara; Wylie, Dennis; DiPietro, Christopher P; Tsatsani, Ioulia; Chen, Chia-Yen; Pernia, Cameron D; Soliva-Estruch, Marina; Arasappan, Dhivya; Bharadwaj, Rahul A; Collado-Torres, Leonardo; Wuchty, Stefan; Alvarez, Victor E; Dammer, Eric B; Deep-Soboslay, Amy; Duong, Duc M; Eagles, Nick; Huber, Bertrand R; Huuki, Louise; Holstein, Vincent L; Logue, Mark W; Lugenbühl, Justina F; Maihofer, Adam X; Miller, Mark W; Nievergelt, Caroline M; Pertea, Geo; Ross, Deanna; Sendi, Mohammad S E; Sun, Benjamin B; Tao, Ran; Tooke, James; Wolf, Erika J; Zeier, Zane; Berretta, Sabina; Champagne, Frances A; Hyde, Thomas; Seyfried, Nicholas T; Shin, Joo Heon; Weinberger, Daniel R; Nemeroff, Charles B; Kleinman, Joel E; Ressler, Kerry J.
Affiliation
  • Daskalakis NP; McLean Hospital, Belmont, MA 02478, USA.
  • Iatrou A; Department of Psychiatry, Harvard Medical School, Boston, MA 02115, USA.
  • Chatzinakos C; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Jajoo A; McLean Hospital, Belmont, MA 02478, USA.
  • Snijders C; Department of Psychiatry, Harvard Medical School, Boston, MA 02115, USA.
  • Wylie D; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • DiPietro CP; McLean Hospital, Belmont, MA 02478, USA.
  • Tsatsani I; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Chen CY; Department of Psychiatry and Behavioral Sciences, SUNY Downstate Health Sciences University, Brooklyn, NY 11203, USA.
  • Pernia CD; VA New York Harbor Healthcare System, Brooklyn, NY 11209, USA.
  • Soliva-Estruch M; McLean Hospital, Belmont, MA 02478, USA.
  • Arasappan D; Department of Psychiatry, Harvard Medical School, Boston, MA 02115, USA.
  • Bharadwaj RA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Collado-Torres L; McLean Hospital, Belmont, MA 02478, USA.
  • Wuchty S; Department of Psychiatry, Harvard Medical School, Boston, MA 02115, USA.
  • Alvarez VE; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Dammer EB; Center for Biomedical Research Support, The University of Texas at Austin, Austin, TX 78712, USA.
  • Deep-Soboslay A; McLean Hospital, Belmont, MA 02478, USA.
  • Duong DM; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Eagles N; McLean Hospital, Belmont, MA 02478, USA.
  • Huber BR; Department of Psychiatry, Harvard Medical School, Boston, MA 02115, USA.
  • Huuki L; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Holstein VL; Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Maastricht University, Maastricht, 6229 ER, Netherlands.
  • Logue MW; Biogen Inc., Cambridge, MA 02142, USA.
  • Lugenbühl JF; McLean Hospital, Belmont, MA 02478, USA.
  • Maihofer AX; Department of Psychiatry, Harvard Medical School, Boston, MA 02115, USA.
  • Miller MW; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Nievergelt CM; McLean Hospital, Belmont, MA 02478, USA.
  • Pertea G; Department of Psychiatry, Harvard Medical School, Boston, MA 02115, USA.
  • Ross D; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Sendi MSE; Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Maastricht University, Maastricht, 6229 ER, Netherlands.
  • Sun BB; Center for Biomedical Research Support, The University of Texas at Austin, Austin, TX 78712, USA.
  • Tao R; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA.
  • Tooke J; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA.
  • Wolf EJ; Departments of Computer Science, University of Miami, Miami, FL 33146, USA.
  • Zeier Z; Department of Biology, University of Miami, Miami, FL 33146, USA.
  • Berretta S; VA Bedford Healthcare System, Bedford, MA 01730, USA.
  • Champagne FA; National Posttraumatic Stress Disorder Brain Bank, VA Boston Healthcare System, Boston, MA 02130, USA.
  • Hyde T; Department of Biochemistry, Center for Neurodegenerative Disease, Emory School of Medicine, Atlanta GA 30329, USA.
  • Seyfried NT; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA.
  • Shin JH; Department of Biochemistry, Center for Neurodegenerative Disease, Emory School of Medicine, Atlanta GA 30329, USA.
  • Weinberger DR; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA.
  • Nemeroff CB; Department of Neurology, Boston University, Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA.
  • Kleinman JE; National Posttraumatic Stress Disorder Brain Bank, VA Boston Healthcare System, Boston, MA 02130, USA.
  • Ressler KJ; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA.
Science ; 384(6698): eadh3707, 2024 May 24.
Article in En | MEDLINE | ID: mdl-38781393
ABSTRACT
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Stress Disorders, Post-Traumatic / Brain / Depressive Disorder, Major / Genetic Loci Limits: Female / Humans / Male Language: En Journal: Science Year: 2024 Type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Stress Disorders, Post-Traumatic / Brain / Depressive Disorder, Major / Genetic Loci Limits: Female / Humans / Male Language: En Journal: Science Year: 2024 Type: Article Affiliation country: United States