Resting-State Functional Connectivity of the Amygdala and Hippocampus in PTSD: Results From the PGC-ENIGMA PTSD Working Group.
| Title: | Resting-State Functional Connectivity of the Amygdala and Hippocampus in PTSD: Results From the PGC-ENIGMA PTSD Working Group. |
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| Authors: | Hinojosa CA; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta.; Sun D; Brain Imaging and Analysis Center, Duke University, Durham, NC.; VA Mid-Atlantic Mental Illness Research, Education, and Clinical Center, Durham, NC.; Department of Psychiatry and Behavioral Sciences, School of Medicine, Duke University, Durham, NC.; Russell C; Brain Imaging and Analysis Center, Duke University, Durham, NC.; VA Mid-Atlantic Mental Illness Research, Education, and Clinical Center, Durham, NC.; Baird CL; Brain Imaging and Analysis Center, Duke University, Durham, NC.; VA Mid-Atlantic Mental Illness Research, Education, and Clinical Center, Durham, NC.; Department of Psychology, Pennsylvania State University, State College.; Hussain A; Brain Imaging and Analysis Center, Duke University, Durham, NC.; VA Mid-Atlantic Mental Illness Research, Education, and Clinical Center, Durham, NC.; Sendi M; Division of Depression and Anxiety Disorders, McLean Hospital, Belmont, MA.; Department of Psychiatry, Harvard Medical School, Boston.; Jahanshad N; Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, Marina del Rey, CA.; Salminen LE; Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, Marina del Rey, CA.; Olff M; Department of Psychiatry, Amsterdam Neuroscience, Amsterdam UMC University of Amsterdam, Amsterdam.; ARQ National Psychotrauma Center, Diemen, the Netherlands.; Frijling JL; Department of Psychiatry, Amsterdam Neuroscience, Amsterdam UMC University of Amsterdam, Amsterdam.; De Viersprong Personality Disorders Institute, Amsterdam.; Veltman DJ; Department of Psychiatry, Amsterdam Neuroscience, Amsterdam UMC University of Amsterdam, Amsterdam.; Department of Psychiatry, Amsterdam Neuroscience, Amsterdam UMC Vrije Universiteit, Amsterdam.; Koch SBJ; Department of Psychiatry, Amsterdam Neuroscience, Amsterdam UMC University of Amsterdam, Amsterdam.; Donders Institute for Brain, Cognition, and Behavior, Center for Cognitive Neuroimaging, Radboud University Nijmegen, Nijmegen, the Netherlands.; Nawijn L; Department of Psychiatry, Amsterdam Neuroscience, Amsterdam UMC University of Amsterdam, Amsterdam.; van Zuiden M; Department of Psychiatry, Amsterdam Neuroscience, Amsterdam UMC University of Amsterdam, Amsterdam.; Department of Clinical Psychology, Utrecht University, Utrecht, the Netherlands.; Wang L; Laboratory for Traumatic Stress Studies, Chinese Academy of Sciences Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing.; Department of Psychology, University of Chinese Academy of Sciences, Beijing.; Zhu Y; Laboratory for Traumatic Stress Studies, Chinese Academy of Sciences Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing.; Department of Psychology, University of Chinese Academy of Sciences, Beijing.; Li G; Laboratory for Traumatic Stress Studies, Chinese Academy of Sciences Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing.; Department of Psychology, University of Chinese Academy of Sciences, Beijing.; Stein DJ; SA MRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.; Ipser J; SA MRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.; Koopowitz SM; SA MRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.; Neria Y; Department of Psychiatry, Columbia University Medical Center, New York.; New York State Psychiatric Institute, New York.; Zhu X; Department of Psychiatry, Columbia University Medical Center, New York.; New York State Psychiatric Institute, New York.; Ravid O; New York State Psychiatric Institute, New York.; Zilcha-Mano S; Department of Psychology, University of Haifa, Haifa, Israel.; Lazarov A; Department of Psychiatry, Columbia University Medical Center, New York.; School of Psychological Sciences, Tel-Aviv University, Tel Aviv-Yafo, Israel.; Suarez-Jimenez B; Department of Neuroscience, University of Rochester Medical Center, Rochester, NY.; Huggins AA; Department of Psychology, University of Arizona, Tucson.; Ressler K; Division of Depression and Anxiety Disorders, McLean Hospital, Belmont, MA.; Department of Psychiatry, Harvard Medical School, Boston.; Jovanovic T; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta.; Department of Psychiatry and Behavioral Neuroscience, Wayne State University School of Medicine, Detroit.; Fani N; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta.; Mueller SC; Department of Experimental Clinical and Health Psychology, Ghent University, Ghent, Belgium.; Hudson AR; Department of Experimental Clinical and Health Psychology, Ghent University, Ghent, Belgium.; Daniels JK; Department of Clinical Psychology, University of Groningen, Groningen, the Netherlands.; Traumacentrum Beilen, GGZ Drenthe, the Netherlands.; Sierk A; Research Division of Mind and Brain, University Medical Center Charité, Berlin.; Manthey A; Research Division of Mind and Brain, University Medical Center Charité, Berlin.; Walter H; Research Division of Mind and Brain, University Medical Center Charité, Berlin.; van der Wee NJA; Department of Psychiatry, Leiden University Medical Center, Leiden, the Netherlands.; Leiden Institute for Brain and Cognition, Leiden, the Netherlands.; van der Werff SJA; Department of Psychiatry, Leiden University Medical Center, Leiden, the Netherlands.; Leiden Institute for Brain and Cognition, Leiden, the Netherlands.; Vermeiren RRJM; Department of Child and Adolescent Psychiatry, Leiden University Medical Center, Leiden, the Netherlands.; Rektor I; Multimodal and Functional Neuroimaging Research Group, Central European Institute of Technology, Masaryk University, Brno, Czech Republic.; Říha P; Multimodal and Functional Neuroimaging Research Group, Central European Institute of Technology, Masaryk University, Brno, Czech Republic.; First Department of Neurology, St. Anne's University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic.; Kaufman ML; Department of Psychiatry, Harvard Medical School, Boston.; Division of Women's Mental Health, McLean Hospital, Belmont, MA.; Lebois LAM; Division of Depression and Anxiety Disorders, McLean Hospital, Belmont, MA.; Department of Psychiatry, Harvard Medical School, Boston.; Baker JT; Department of Psychiatry, Harvard Medical School, Boston.; Institute for Technology in Psychiatry, McLean Hospital, Belmont, MA.; King A; Department of Psychiatry, University of Michigan, Ann Arbor.; Liberzon I; Department of Psychiatry and Behavioral Science, Texas A&M University Health Science Center, Bryan.; Angstadt M; Department of Psychiatry, University of Michigan, Ann Arbor.; Davenport ND; Minneapolis VA Health Care System, Minneapolis.; Department of Psychiatry, University of Minnesota, Minneapolis.; Disner SG; Minneapolis VA Health Care System, Minneapolis.; Department of Psychiatry, University of Minnesota, Minneapolis.; Sponheim SR; Minneapolis VA Health Care System, Minneapolis.; Straube T; Institute of Medical Psychology and Systems Neuroscience, University of Münster, Münster, Germany.; Hofmann D; Institute of Medical Psychology and Systems Neuroscience, University of Münster, Münster, Germany.; Lu GM; Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.; Qi R; Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.; Wang X; Department of Psychiatry, University of Toledo, Toledo, OH.; Kunch A; Department of Psychiatry, University of Toledo, Toledo, OH.; Xie H; Department of Psychiatry, University of Toledo, Toledo, OH.; Quidé Y; School of Psychology, University of New South Wales, Sydney, Australia.; Neuroscience Research Australia, Randwick, Australia.; El-Hage W; UMR1253, iBraiN, Université de Tours, Inserm, Tours, France.; Lissek S; Department of Psychology, University of Minnesota, Minneapolis.; Berg H; Department of Psychology, University of Minnesota, Minneapolis.; Cisler J; Department of Psychiatry, University of Texas at Austin, Austin.; Ross M; Northwestern Neighborhood and Network Initiative, Northwestern University Institute for Policy Research, Evanston, IL.; Herringa RJ; Department of Psychiatry, School of Medicine and Public Health, University of Wisconsin-Madison, Madison.; Grupe DW; Center for Healthy Minds, University of Wisconsin-Madison, Madison.; Nitschke JB; Department of Psychiatry, University of Wisconsin-Madison, Madison.; Davidson RJ; Center for Healthy Minds, University of Wisconsin-Madison, Madison.; Department of Psychiatry, University of Wisconsin-Madison, Madison.; Department of Psychology, University of Wisconsin-Madison, Madison.; Larson CL; Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee.; deRoon-Cassini TA; Division of Trauma and Acute Care Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee.; Comprehensive Injury Center, Medical College of Wisconsin, Milwaukee.; Tomas CW; Department of Epidemiology, Institute of Health and Equity, Medical College of Wisconsin, Milwaukee.; Comprehensive Injury Center, Medical College of Wisconsin, Milwaukee.; Fitzgerald JM; Department of Psychology, Marquette University, Milwaukee.; Feola B; Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN.; Urbano-Blackford J; Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN.; Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha.; Olatunji BO; Department of Psychology, Vanderbilt University, Nashville, TN.; May G; Center for Vital Longevity, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas.; Department of Psychology and Neuroscience, Baylor University, Waco, TX.; Veterans Integrated Service Network 17 Center of Excellence for Research on Returning War Veterans, Waco, TX.; Nelson SM; Department of Psychiatry and Behavioral Science, Texas A&M University Health Science Center, Bryan.; Center for Vital Longevity, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas.; Department of Psychology and Neuroscience, Baylor University, Waco, TX.; Veterans Integrated Service Network 17 Center of Excellence for Research on Returning War Veterans, Waco, TX.; Gordon EM; Department of Radiology, Washington University School of Medicine, St. Louis.; Abdallah CG; Department of Psychiatry, Baylor College of Medicine, Houston.; Department of Psychiatry, Yale University School of Medicine, New Haven, CT.; Lanius R; Department of Neuroscience, Western University, London.; Department of Psychiatry, Western University, London.; Densmore M; Department of Psychiatry, Western University, London.; Théberge J; Department of Psychiatry, Western University, London.; Neufeld RWJ; Department of Psychiatry, Western University, London.; Baugh LA; Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion.; Center for Brain and Behavior Research, University of South Dakota, Vermillion.; Sioux Falls VA Health Care System, Sioux Falls, SD.; Simons RM; Center for Brain and Behavior Research, University of South Dakota, Vermillion.; Department of Psychology, University of South Dakota, Vermillion.; Simons JS; Sioux Falls VA Health Care System, Sioux Falls, SD.; Department of Psychology, University of South Dakota, Vermillion.; Magnotta VA; Departments of Radiology, Psychiatry, and Biomedical Engineering, University of Iowa, Iowa City.; Fercho KA; Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion.; Center for Brain and Behavior Research, University of South Dakota, Vermillion.; Civil Aerospace Medical Institute, US Federal Aviation Administration, Oklahoma City.; Elman J; Department of Psychiatry, University of California San Diego, La Jolla.; Stein Institute for Research on Aging and Center for Healthy Aging, University of California San Diego, La Jolla.; Panizzon M; Department of Psychiatry, University of California San Diego, La Jolla.; Franz C; Department of Psychiatry, University of California, San Diego, La Jolla.; Center for Behavioral Genetics of Aging, University of California San Diego, La Jolla.; Lyons MJ; Department of Psychological and Brain Sciences, Boston University, Boston.; Kremen W; Department of Psychiatry, University of California, San Diego, La Jolla.; Center for Behavioral Genetics of Aging, University of California San Diego, La Jolla.; Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, La Jolla, CA.; McLaughin KA; Department of Psychology, Harvard University, Cambridge, MA.; Peverill M; Department of Psychology, University of Washington, Seattle.; Sambrook K; Department of Radiology, University of Washington, Seattle.; Thompson PM; Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, Marina del Rey, CA.; Stevens JS; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta.; Morey RA; Brain Imaging and Analysis Center, Duke University, Durham, NC.; VA Mid-Atlantic Mental Illness Research, Education, and Clinical Center, Durham, NC.; van Rooij SJH; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta. |
| Source: | The American journal of psychiatry [Am J Psychiatry] 2026 May 01; Vol. 183 (5), pp. 333-342. Date of Electronic Publication: 2026 Apr 02. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: American Psychiatric Association Country of Publication: United States NLM ID: 0370512 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1535-7228 (Electronic) Linking ISSN: 0002953X NLM ISO Abbreviation: Am J Psychiatry Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Arlington, VA : American Psychiatric Association |
| MeSH Terms: | Stress Disorders, Post-Traumatic*/physiopathology ; Stress Disorders, Post-Traumatic*/diagnostic imaging ; Amygdala*/physiopathology ; Amygdala*/diagnostic imaging ; Hippocampus*/physiopathology ; Hippocampus*/diagnostic imaging; Neural Pathways/physiopathology ; Neural Pathways/diagnostic imaging ; Humans ; Magnetic Resonance Imaging ; Male ; Female ; Adult ; Middle Aged ; Connectome |
| Abstract: | Objective: Studies investigating resting-state functional connectivity of the amygdala and hippocampus have produced inconsistent findings. The authors' objective was to conduct the largest systematic comparison of alterations in functional connectivity of the amygdala and hippocampus in individuals with posttraumatic stress disorder (PTSD) using a multicohort mega-analysis with uniform processing steps and parameters across all cohorts.; Methods: Resting-state functional MRI data from 1,017 PTSD patients and 1,702 control participants from 32 international sites were centrally preprocessed with HALFpipe and analyzed using the Image-Based Meta- and Mega-Analysis (IBMMA) package for neuroimaging processing. Group-level seed-based whole-brain analyses were completed for the right and left amygdala and hippocampus. Additional correlation analyses were conducted between PTSD norm-severity scores and resting-state functional connectivity (rs-FC).; Results: Compared to control participants, individuals with PTSD showed stronger rs-FC between the left amygdala seed and right hippocampus and amygdala and the left and right lingual gyri. Greater PTSD total norm-severity scores were significantly associated with rs-FC between the left amygdala and right hippocampus/amygdala and rs-FC between the right amygdala and left hippocampus/amygdala.; Conclusions: Greater connectivity between subcortical threat centers involved in fear processing, memory, and extinction learning characterizes the resting state in PTSD. Future directions include investigating how different interventions, such as brain stimulation, neurofeedback, and psychotherapy, might modulate the aberrant neural networks in PTSD. |
| Competing Interests: | Dr. Sendi has served as a consultant for Niji Corp and is the co-founder of Vitalytic AI. Dr. Jahanshad has received research support from Biogen. Dr. Stein has received consultancy honoraria from Discovery Vitality, Johnson & Johnson, Kanna, L’Oreal, Lundbeck, Orion, Sanofi, Servier, Takeda, and Vistagen. Dr. Walter has received honoraria and loyalties from Becker Joest Volk Verlag, Hilden, Thieme Verlag Stuttgart, and Springer Verlag Heidelberg, and lecture and related travel fees from Academy of Neuroscience, Köln, Rovi-GmbH, Holzkirchen, and Psi-Fit GmbH, Wolfsburg. Dr. Lebois has served as an unpaid member of the Scientific Committee for the International Society for the Study of Trauma and Dissociation, and she reports spousal IP payments from Vanderbilt University for technology licensed to Acadia Pharmaceuticals and spousal private equity in Violet Therapeutics. Dr. Baker has received consulting fees from and has an equity stake in Tetricus Labs. Dr. El-Hage has received payments from Air Liquide, Chugai, Eisai, Jazz Pharmaceuticals, Janssen, Lundbeck, Otsuka, and UCB. Dr. Herringa has served as a consultant for Jazz Pharmaceuticals. Dr. Abdallah has served as a consultant, speaker, and/or on advisory boards for Douglas Pharmaceuticals, Freedom Biosciences, FSV7, Lundbeck, Psilocybin Labs, Genentech, and Janssen; and he has filed a patent for using mTOR inhibitors to augment the effects of antidepressants. Dr. Magnotta has received research support from GE Healthcare and SpinTech. Dr. Thompson received partial research support from Biogen. The other authors report no financial relationships with commercial interests. |
| Grant Information: | R21 MH125277 United States MH NIMH NIH HHS |
| Contributed Indexing: | Keywords: Neuroimaging; Posttraumatic Stress Disorder (PTSD) |
| Entry Date(s): | Date Created: 20260402 Date Completed: 20260501 Latest Revision: 20260501 |
| Update Code: | 20260501 |
| DOI: | 10.1176/appi.ajp.20250062 |
| PMID: | 41922983 |
| Database: | MEDLINE |
Journal Article