Systems biology dissection of PTSD and MDD across brain regions, cell types, and blood

著者: Nikolaos P. Daskalakis, Artemis Iatrou, Chris Chatzinakos, Aarti Jajoo, Clara Snijders, Dennis Wylie, Christopher P. DiPietro, Ioulia Tsatsani, Chia‐Yen Chen, Cameron D. Pernia, Marina Soliva-Estruch, Dhivya Arasappan, Rahul Bharadwaj, Leonardo Collado‐Torres, Stefan Wuchty, Victor E. Alvarez, Eric B. Dammer, Amy Deep‐Soboslay, Duc M. Duong, Marina Soliva-Estruch, Bertrand R. Huber, Louise A. Huuki-Myers, Vincent Holstein, Mark W. Logue, Justina F. Lugenbühl, Adam X. Maihofer, Mark W. Miller, Caroline M. Nievergelt, Geo Pertea, Deanna Ross, Mohammad S.E. Sendi, Benjamin B. Sun, Ran Tao, J. E. Tooke, Erika J. Wolf, Zane Zeier, Sabina Berretta, Frances A. Champagne, Thomas M. Hyde, Nicholas T. Seyfried, Joo Heon Shin, Daniel R. Weinberger, Charles B. Nemeroff, Joel E. Kleinman, Kerry J. Ressler, Caroline M. Nievergelt, Adam X. Maihofer, Elizabeth G. Atkinson, Chia‐Yen Chen, Karmel W. Choi, Jonathan R. I. Coleman, Nikolaos P. Daskalakis, Laramie E. Duncan, Renato Polimanti, Cindy Aaronson, Ananda B. Amstadter, Søren Bo Andersen, Ole A. Andreassen, Paul A. Arbisi, Allison E. Ashley‐Koch, S. Bryn Austin, Esmina Avdibegović, Dragan Babić, Silviu‐Alin Bacanu, Dewleen G. Baker, Anthony Batzler, Jean C. Beckham, Síntia Belangero, Corina Benjet, Carisa Bergner, Linda M. Bierer, Joanna M. Biernacka, Laura J. Bierut, Jonathan I. Bisson, Marco P. Boks, Elizabeth Bolger, Amber Brandolino, Gerome Breen, Rodrigo A. Bressan, Richard A. Bryant, Angela C. Bustamante, Jonas Bybjerg‐Grauholm, Marie Bækvad‐Hansen, Anders D. Børglum, Sigrid Børte, Leah Cahn, Joseph R. Calabrese, José Miguel Caldas‐de‐Almeida, Chris Chatzinakos, Sheraz Cheema, Sean Clouston, Lucía Colodro‐Conde, Brandon J. Coombes, Carlos S. Cruz-Fuentes, Anders M. Dale, Shareefa Dalvie, Lea K. Davis, Jürgen Deckert, Douglas L. Delahanty, Michelle F. Dennis, Frank Désarnaud, Christopher P. DiPietro, Seth G. Disner, Anna R. Docherty, Katharina Domschke, Grete Dyb, Alma Džubur Kulenović, Howard J. Edenberg, Alexandra Evans, Chiara Fabbri, Negar Fani, Lindsay A. Farrer, Adriana Feder, Norah C. Feeny, Janine D. Flory, David Forbes, Carol E. Franz, Sandro Galea, Melanie E. Garrett, Bizu Gelaye, Joel Gelernter, Elizabeth A. Bolger, Charles F. Gillespie, Slavina B. Goleva, Scott D. Gordon, Afërdita Goçi, Lana Ruvolo Grasser, Camila Guindalini, Magali Haas, Saskia P. Hagenaars, Michael A. Hauser, Andrew C. Heath, Sian Hemmings, Victor Hesselbrock, Ian B. Hickie, Kelleigh Hogan, David M. Hougaard, Hailiang Huang, Laura M. Huckins, Kristian Hveem, Miro Jakovljević, Arash Javanbakht, Gregory D. Jenkins, Jessica Johnson, Ian Jones, Tanja Jovanović, Karen‐Inge Karstoft, Milissa L. Kaufman, James L. Kennedy, Ronald C. Kessler, Alaptagin Khan, Nathan A. Kimbrel, Anthony P. King, Nastassja Koen, Roman Kotov, Henry R. Kranzler, Kristi Krebs, William S. Kremen, Pei Fen Kuan, Bruce R. Lawford, Lauren A. M. Lebois, Kelli Lehto, Daniel F. Levey, David Forbes, Israel Liberzon, Sarah D. Linnstaedt, Mark W. Logue, Adriana Lori, Yi Lu, Benjamin J. Luft, Michelle K. Lupton, Jurjen J. Luykx, Iouri Makotkine, Jessica L. Maples‐Keller, Shelby Marchese, Charles R. Marmar, Nicholas G. Martin, Gabriela Ariadna Martínez-Levy, Kerrie McAloney, Alexander C. McFarlane, Katie A. McLaughlin, Samuel A. McLean, Sarah E. Medland, Divya Mehta, Jacquelyn L. Meyers, Vasiliki Michopoulos, Elizabeth A. Mikita, Lili Milani, William Milberg, Mark W. Miller, Rajendra A. Morey, C. Phillip Morris, Ole Mors, Preben Bo Mortensen, Mary S. Mufford, Elliot C. Nelson, Merete Nordentoft, Sonya B. Norman, Nicole R. Nugent, Meaghan O’Donnell, Holly K. Orcutt, Pedro Mário Pan, Matthew S. Panizzon, Gita A. Pathak, Edward Peters, Alan L. Peterson, Matthew Peverill, Robert H. Pietrzak, Melissa A. Polusny, Bernice Porjesz, Abigail Powers, Xuejun Qin, Andrew Ratanatharathorn, Victoria B. Risbrough, Andrea L. Roberts, Alex O. Rothbaum, Barbara O. Rothbaum, Peter Roy‐Byrne, Kenneth J. Ruggiero, Ariane L. Rung, Heiko Runz, Bart P. F. Rutten, Stacey Saenz de Viteri, Giovanni Abrahão Salum, Laura Sampson, Sixto E. Sánchez, Marcos Santoro, Carina Seah, Soraya Seedat, Julia S. Seng, Andrey A. Shabalin, Christina M. Sheerin, Derrick Silove, Alicia K. Smith, Jordan W. Smoller, Scott R. Sponheim, Dan J. Stein, Synne Øien Stensland, Jennifer S. Stevens, Jennifer A. Sumner, Martin H. Teicher, Wesley K. Thompson, Arun K. Tiwari, Edward Trapido, Monica Uddin, Robert J. Ursano, Unnur Valdimarsdóttir, Miranda Van Hooff, Eric Vermetten, Christiaan H. Vinkers, Joanne Voisey, Yunpeng Wang, Zhewu Wang, Monika A. Waszczuk, Heike Weber, Frank R. Wendt, Thomas Werge, Michelle A. Williams, Douglas E. Williamson, Bendik S. Winsvold, Sherry Winternitz, Christiane Wolf, Erika J. Wolf, Yan Xia, Ying Xiong, Rachel Yehuda, Keith A. Young, Ross McD. Young, Clement C. Zai, Gwyneth Zai, Mark Zervas, Hongyu Zhao, Lori A. Zoellner, John‐Anker Zwart, Terri A. deRoon‐Cassini, Sanne J.H. van Rooij, Leigh L. van den Heuvel, Carina Seah, Soraya Seedat, Julia S. Seng, Andrey Shabalin, Christina M. Sheerin, Derrick Silove, Alicia K. Smith, Jordan W. Smoller, Scott R. Sponheim, Dan J. Stein, Synne Øien Stensland, Jennifer S. Stevens, Jennifer A. Sumner, Martin H. Teicher, Wesley K. Thompson, Arun K. Tiwari, Edward Trapido, Monica Uddin, Robert J. Ursano, Unnur Valdimarsdóttir, Miranda Van Hooff, Eric Vermetten, Christiaan H. Vinkers, Joanne Voisey, Yunpeng Wang, Zhewu Wang, Monika A. Waszczuk, Heike Weber, Frank R. Wendt, Thomas Werge, Michelle A. Williams, Douglas E. Williamson, Bendik S. Winsvold, Sherry Winternitz, Christiane Wolf, Erika J. Wolf, Erika J. Wolf, Yan Xia, Ying Xiong, Rachel Yehuda, Keith A. Young, Ross McD. Young, Clement C. Zai, Gwyneth Zai, Mark Zervas, Hongyu Zhao, Lori A. Zoellner, John‐Anker Zwart, Terri A. deRoon‐Cassini, Sanne J.H. van Rooij, Leigh L. van den Heuvel, AURORA Study, FinnGen Investigators, HUNT All-In Psychiatry, Murray B. Stein, Kerry J. Ressler, Karestan C. Koenen - Science 2024 被引用: 84

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.