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

Humans Depressive Disorder, Major / genetics Stress Disorders, Post-Traumatic / genetics Genome-Wide Association Study Prefrontal Cortex / metabolism Systems Biology Male Brain Female Adult Gene Regulatory Networks Middle Aged Neurons / metabolism Biomarkers / blood Amygdala

Journal

Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511

Informations de publication

Date de publication:
24 May 2024
Historique:
medline: 23 5 2024
pubmed: 23 5 2024
entrez: 23 5 2024
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1126/science.adh3707 PMID: 38781393
pubmed: 38781393
doi: 10.1126/science.adh3707
doi:

Substances chimiques

Biomarkers 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

eadh3707

Investigateurs

Caroline M Nievergelt (CM)
Adam X Maihofer (AX)
Elizabeth G Atkinson (EG)
Chia-Yen Chen (CY)
Karmel W Choi (KW)
Jonathan R I Coleman (JRI)
Nikolaos P Daskalakis (NP)
Laramie E Duncan (LE)
Renato Polimanti (R)
Cindy Aaronson (C)
Ananda B Amstadter (AB)
Soren B Andersen (SB)
Ole A Andreassen (OA)
Paul A Arbisi (PA)
Allison E Ashley-Koch (AE)
S Bryn Austin (SB)
Esmina Avdibegoviç (E)
Dragan Babić (D)
Silviu-Alin Bacanu (SA)
Dewleen G Baker (DG)
Anthony Batzler (A)
Jean C Beckham (JC)
Sintia Belangero (S)
Corina Benjet (C)
Carisa Bergner (C)
Linda M Bierer (LM)
Joanna M Biernacka (JM)
Laura J Bierut (LJ)
Jonathan I Bisson (JI)
Marco P Boks (MP)
Elizabeth A Bolger (EA)
Amber Brandolino (A)
Gerome Breen (G)
Rodrigo Affonseca Bressan (RA)
Richard A Bryant (RA)
Angela C Bustamante (AC)
Jonas Bybjerg-Grauholm (J)
Marie Bækvad-Hansen (M)
Anders D Børglum (AD)
Sigrid Børte (S)
Leah Cahn (L)
Joseph R Calabrese (JR)
Jose Miguel Caldas-de-Almeida (JM)
Chris Chatzinakos (C)
Sheraz Cheema (S)
Sean A P Clouston (SAP)
Lucía Colodro-Conde (L)
Brandon J Coombes (BJ)
Carlos S Cruz-Fuentes (CS)
Anders M Dale (AM)
Shareefa Dalvie (S)
Lea K Davis (LK)
Jürgen Deckert (J)
Douglas L Delahanty (DL)
Michelle F Dennis (MF)
Frank Desarnaud (F)
Christopher P DiPietro (CP)
Seth G Disner (SG)
Anna R Docherty (AR)
Katharina Domschke (K)
Grete Dyb (G)
Alma Džubur Kulenović (AD)
Howard J Edenberg (HJ)
Alexandra Evans (A)
Chiara Fabbri (C)
Negar Fani (N)
Lindsay A Farrer (LA)
Adriana Feder (A)
Norah C Feeny (NC)
Janine D Flory (JD)
David Forbes (D)
Carol E Franz (CE)
Sandro Galea (S)
Melanie E Garrett (ME)
Bizu Gelaye (B)
Joel Gelernter (J)
Elbert Geuze (E)
Charles F Gillespie (CF)
Slavina B Goleva (SB)
Scott D Gordon (SD)
Aferdita Goçi (A)
Lana Ruvolo Grasser (LR)
Camila Guindalini (C)
Magali Haas (M)
Saskia Hagenaars (S)
Michael A Hauser (MA)
Andrew C Heath (AC)
Sian M J Hemmings (SMJ)
Victor Hesselbrock (V)
Ian B Hickie (IB)
Kelleigh Hogan (K)
David Michael Hougaard (DM)
Hailiang Huang (H)
Laura M Huckins (LM)
Kristian Hveem (K)
Miro Jakovljević (M)
Arash Javanbakht (A)
Gregory D Jenkins (GD)
Jessica Johnson (J)
Ian Jones (I)
Tanja Jovanovic (T)
Karen-Inge Karstoft (KI)
Milissa L Kaufman (ML)
James L Kennedy (JL)
Ronald C Kessler (RC)
Alaptagin Khan (A)
Nathan A Kimbrel (NA)
Anthony P King (AP)
Nastassja Koen (N)
Roman Kotov (R)
Henry R Kranzler (HR)
Kristi Krebs (K)
William S Kremen (WS)
Pei-Fen Kuan (PF)
Bruce R Lawford (BR)
Lauren A M Lebois (LAM)
Kelli Lehto (K)
Daniel F Levey (DF)
Catrin Lewis (C)
Israel Liberzon (I)
Sarah D Linnstaedt (SD)
Mark W Logue (MW)
Adriana Lori (A)
Yi Lu (Y)
Benjamin J Luft (BJ)
Michelle K Lupton (MK)
Jurjen J Luykx (JJ)
Iouri Makotkine (I)
Jessica L Maples-Keller (JL)
Shelby Marchese (S)
Charles Marmar (C)
Nicholas G Martin (NG)
Gabriela A Martínez-Levy (GA)
Kerrie McAloney (K)
Alexander McFarlane (A)
Katie A McLaughlin (KA)
Samuel A McLean (SA)
Sarah E Medland (SE)
Divya Mehta (D)
Jacquelyn Meyers (J)
Vasiliki Michopoulos (V)
Elizabeth A Mikita (EA)
Lili Milani (L)
William Milberg (W)
Mark W Miller (MW)
Rajendra A Morey (RA)
Charles Phillip Morris (CP)
Ole Mors (O)
Preben Bo Mortensen (PB)
Mary S Mufford (MS)
Elliot C Nelson (EC)
Merete Nordentoft (M)
Sonya B Norman (SB)
Nicole R Nugent (NR)
Meaghan O'Donnell (M)
Holly K Orcutt (HK)
Pedro M Pan (PM)
Matthew S Panizzon (MS)
Gita A Pathak (GA)
Edward S Peters (ES)
Alan L Peterson (AL)
Matthew Peverill (M)
Robert H Pietrzak (RH)
Melissa A Polusny (MA)
Bernice Porjesz (B)
Abigail Powers (A)
Xue-Jun Qin (XJ)
Andrew Ratanatharathorn (A)
Victoria B Risbrough (VB)
Andrea L Roberts (AL)
Alex O Rothbaum (AO)
Barbara O Rothbaum (BO)
Peter Roy-Byrne (P)
Kenneth J Ruggiero (KJ)
Ariane Rung (A)
Heiko Runz (H)
Bart P F Rutten (BPF)
Stacey Saenz de Viteri (SS)
Giovanni Abrahão Salum (GA)
Laura Sampson (L)
Sixto E Sanchez (SE)
Marcos Santoro (M)
Carina Seah (C)
Soraya Seedat (S)
Julia S Seng (JS)
Andrey Shabalin (A)
Christina M Sheerin (CM)
Derrick Silove (D)
Alicia K Smith (AK)
Jordan W Smoller (JW)
Scott R Sponheim (SR)
Dan J Stein (DJ)
Synne Stensland (S)
Jennifer S Stevens (JS)
Jennifer A Sumner (JA)
Martin H Teicher (MH)
Wesley K Thompson (WK)
Arun K Tiwari (AK)
Edward Trapido (E)
Monica Uddin (M)
Robert J Ursano (RJ)
Unnur Valdimarsdóttir (U)
Miranda Van Hooff (M)
Eric Vermetten (E)
Christiaan H Vinkers (CH)
Joanne Voisey (J)
Yunpeng Wang (Y)
Zhewu Wang (Z)
Monika Waszczuk (M)
Heike Weber (H)
Frank R Wendt (FR)
Thomas Werge (T)
Michelle A Williams (MA)
Douglas E Williamson (DE)
Bendik S Winsvold (BS)
Sherry Winternitz (S)
Christiane Wolf (C)
Erika J Wolf (EJ)
Yan Xia (Y)
Ying Xiong (Y)
Rachel Yehuda (R)
Keith A Young (KA)
Ross McD Young (RM)
Clement C Zai (CC)
Gwyneth C Zai (GC)
Mark Zervas (M)
Hongyu Zhao (H)
Lori A Zoellner (LA)
John-Anker Zwart (JA)
Terri deRoon-Cassini (T)
Sanne J H van Rooij (SJH)
Leigh L van den Heuvel (LL)
Murray B Stein (MB)
Kerry J Ressler (KJ)
Karestan C Koenen (KC)

Auteurs

Nikolaos P Daskalakis (NP)

McLean Hospital, Belmont, MA 02478, USA.
Department of Psychiatry, Harvard Medical School, Boston, MA 02115, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Artemis Iatrou (A)

McLean Hospital, Belmont, MA 02478, USA.
Department of Psychiatry, Harvard Medical School, Boston, MA 02115, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Chris Chatzinakos (C)

McLean Hospital, Belmont, MA 02478, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Department of Psychiatry and Behavioral Sciences, SUNY Downstate Health Sciences University, Brooklyn, NY 11203, USA.
VA New York Harbor Healthcare System, Brooklyn, NY 11209, USA.

Aarti Jajoo (A)

McLean Hospital, Belmont, MA 02478, USA.
Department of Psychiatry, Harvard Medical School, Boston, MA 02115, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Clara Snijders (C)

McLean Hospital, Belmont, MA 02478, USA.
Department of Psychiatry, Harvard Medical School, Boston, MA 02115, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Dennis Wylie (D)

Center for Biomedical Research Support, The University of Texas at Austin, Austin, TX 78712, USA.

Christopher P DiPietro (CP)

McLean Hospital, Belmont, MA 02478, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Ioulia Tsatsani (I)

McLean Hospital, Belmont, MA 02478, USA.
Department of Psychiatry, Harvard Medical School, Boston, MA 02115, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Maastricht University, Maastricht, 6229 ER, Netherlands.

Chia-Yen Chen (CY)

Biogen Inc., Cambridge, MA 02142, USA.

Cameron D Pernia (CD)

McLean Hospital, Belmont, MA 02478, USA.
Department of Psychiatry, Harvard Medical School, Boston, MA 02115, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Marina Soliva-Estruch (M)

McLean Hospital, Belmont, MA 02478, USA.
Department of Psychiatry, Harvard Medical School, Boston, MA 02115, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Maastricht University, Maastricht, 6229 ER, Netherlands.

Dhivya Arasappan (D)

Center for Biomedical Research Support, The University of Texas at Austin, Austin, TX 78712, USA.

Rahul A Bharadwaj (RA)

Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA.

Leonardo Collado-Torres (L)

Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA.

Stefan Wuchty (S)

Departments of Computer Science, University of Miami, Miami, FL 33146, USA.
Department of Biology, University of Miami, Miami, FL 33146, USA.

Victor E Alvarez (VE)

Department of Neurology, Boston University, Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA.
VA Bedford Healthcare System, Bedford, MA 01730, USA.
National Posttraumatic Stress Disorder Brain Bank, VA Boston Healthcare System, Boston, MA 02130, USA.

Eric B Dammer (EB)

Department of Biochemistry, Center for Neurodegenerative Disease, Emory School of Medicine, Atlanta GA 30329, USA.

Amy Deep-Soboslay (A)

Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA.

Duc M Duong (DM)

Department of Biochemistry, Center for Neurodegenerative Disease, Emory School of Medicine, Atlanta GA 30329, USA.

Nick Eagles (N)

Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA.

Bertrand R Huber (BR)

Department of Neurology, Boston University, Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA.
National Posttraumatic Stress Disorder Brain Bank, VA Boston Healthcare System, Boston, MA 02130, USA.

Louise Huuki (L)

Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA.

Vincent L Holstein (VL)

McLean Hospital, Belmont, MA 02478, USA.
Department of Psychiatry, Harvard Medical School, Boston, MA 02115, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Mark W Logue (MW)

National Center for PTSD, VA Boston Healthcare System, Boston, MA 02130, USA.
Department of Psychiatry, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA.
Department of Biomedical Genetics, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA.
Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA.

Justina F Lugenbühl (JF)

McLean Hospital, Belmont, MA 02478, USA.
Department of Psychiatry, Harvard Medical School, Boston, MA 02115, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Maastricht University, Maastricht, 6229 ER, Netherlands.

Adam X Maihofer (AX)

Department of Psychiatry, University of California San Diego, La Jolla, CA 92093, USA.
Center for Excellence in Stress and Mental Health, Veterans Affairs San Diego Healthcare System, San Diego, CA 92161, USA.
Research Service, Veterans Affairs San Diego Healthcare System, San Diego, CA 92161, USA.

Mark W Miller (MW)

National Center for PTSD, VA Boston Healthcare System, Boston, MA 02130, USA.
Department of Psychiatry, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA.

Caroline M Nievergelt (CM)

Department of Psychiatry, University of California San Diego, La Jolla, CA 92093, USA.
Center for Excellence in Stress and Mental Health, Veterans Affairs San Diego Healthcare System, San Diego, CA 92161, USA.
Research Service, Veterans Affairs San Diego Healthcare System, San Diego, CA 92161, USA.

Geo Pertea (G)

Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA.

Deanna Ross (D)

Department of Psychology, University of Texas at Austin, Austin, TX 78712, USA.

Mohammad S E Sendi (MSE)

McLean Hospital, Belmont, MA 02478, USA.
Department of Psychiatry, Harvard Medical School, Boston, MA 02115, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Benjamin B Sun (BB)

Biogen Inc., Cambridge, MA 02142, USA.

Ran Tao (R)

Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA.

James Tooke (J)

Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA.

Erika J Wolf (EJ)

National Center for PTSD, VA Boston Healthcare System, Boston, MA 02130, USA.
Department of Psychiatry, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA.

Zane Zeier (Z)

Department of Psychiatry & Behavioral Sciences, Center for Therapeutic Innovation, University of Miami Miller School of Medicine, Miami, FL 33136, USA.

Sabina Berretta (S)

McLean Hospital, Belmont, MA 02478, USA.
Department of Psychiatry, Harvard Medical School, Boston, MA 02115, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Frances A Champagne (FA)

Department of Psychology, University of Texas at Austin, Austin, TX 78712, USA.

Thomas Hyde (T)

Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA.
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine; Baltimore, MD, 21205, USA.
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Nicholas T Seyfried (NT)

Department of Biochemistry, Center for Neurodegenerative Disease, Emory School of Medicine, Atlanta GA 30329, USA.

Joo Heon Shin (JH)

Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA.
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Daniel R Weinberger (DR)

Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA.
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine; Baltimore, MD, 21205, USA.
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Charles B Nemeroff (CB)

Department of Psychology, University of Texas at Austin, Austin, TX 78712, USA.
Department of Psychiatry and Behavioral Sciences, University of Texas at Austin, Austin, TX 78712, USA.

Joel E Kleinman (JE)

Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA.
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine; Baltimore, MD, 21205, USA.

Kerry J Ressler (KJ)

McLean Hospital, Belmont, MA 02478, USA.
Department of Psychiatry, Harvard Medical School, Boston, MA 02115, USA.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Systems biology dissection of PTSD and MDD...
questionsmedicales.fr › Troubles mentaux › Troubles de l'humeur › Trouble dépressif › Trouble dépressif majeur › Systems biology dissection of PTSD and MDD...
questionsmedicales.fr › Troubles mentaux › Troubles liés aux traumatismes et au stress › Troubles de stress traumatique › Troubles de stress post-traumatique › Systems biology dissection of PTSD and MDD...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Systems biology dissection of PTSD and MDD...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Prosencéphale › Télencéphale › Cerveau › Cortex cérébral › Lobe frontal › Cortex préfrontal › Systems biology dissection of PTSD and MDD...
questionsmedicales.fr › Disciplines des sciences naturelles › Disciplines des sciences biologiques › Biologie › Biologie des systèmes › Systems biology dissection of PTSD and MDD...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Systems biology dissection of PTSD and MDD...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Systems biology dissection of PTSD and MDD...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Séquences d'acides nucléiques régulatrices › Réseaux de régulation génique › Systems biology dissection of PTSD and MDD...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Systems biology dissection of PTSD and MDD...
questionsmedicales.fr › Cellules › Neurones › Systems biology dissection of PTSD and MDD...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Systems biology dissection of PTSD and MDD...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Prosencéphale › Télencéphale › Cerveau › Noyaux gris centraux › Amygdale (système limbique) › Systems biology dissection of PTSD and MDD...