Journal article
Resting-State Functional Connectivity of the Amygdala and Hippocampus in PTSD: Results From the PGC-ENIGMA PTSD Working Group
The American journal of psychiatry
04/02/2026
DOI: 10.1176/appi.ajp.20250062
PMID: 41922983
Abstract
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.
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).
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.
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.
Details
- Title: Subtitle
- Resting-State Functional Connectivity of the Amygdala and Hippocampus in PTSD: Results From the PGC-ENIGMA PTSD Working Group
- Creators
- Cecilia A Hinojosa - Emory UniversityDelin Sun - Duke UniversityCourtney Russell - Duke UniversityC Lexi Baird - Pennsylvania State UniversityAhmed Hussain - Duke UniversityMohammad Sendi - Harvard UniversityNeda Jahanshad - Marina Del Rey HospitalLauren E Salminen - Marina Del Rey HospitalMiranda Olff - Arq Psychotrauma Expert GroupJessie L Frijling - Amsterdam NeuroscienceDick J Veltman - Amsterdam NeuroscienceSaskia B J Koch - Radboud University NijmegenLaura Nawijn - Amsterdam NeuroscienceMirjam van Zuiden - Utrecht UniversityLi Wang - Chinese Academy of SciencesYe Zhu - Chinese Academy of SciencesGen Li - Chinese Academy of SciencesDan J Stein - South African Medical Research CouncilJonathan Ipser - University of Cape TownSheri-Michelle Koopowitz - South African Medical Research CouncilYuval Neria - Columbia University Irving Medical CenterXi Zhu - Columbia University Irving Medical CenterOrren Ravid - New York State Psychiatric InstituteSigal Zilcha-Mano - University of HaifaAmit Lazarov - Tel Aviv UniversityBenjamin Suarez-Jimenez - University of Rochester Medical CenterAshley A Huggins - University of ArizonaKerry Ressler - McLean HospitalTanja Jovanovic - Wayne State UniversityNegar Fani - Emory UniversitySven C Mueller - Ghent University HospitalAnna R Hudson - Ghent University HospitalJudith K Daniels - University of GroningenAnika Sierk - Charité - Universitätsmedizin BerlinAntje Manthey - Charité - Universitätsmedizin BerlinHenrik Walter - Charité - Universitätsmedizin BerlinNic J A van der Wee - Leiden University Medical CenterSteven J A van der Werff - Leiden University Medical CenterRobert R J M Vermeiren - Leiden University Medical CenterIvan Rektor - Central European Institute of TechnologyPavel Říha - Masaryk UniversityMilissa L Kaufman - McLean HospitalLauren A M Lebois - Harvard UniversityJustin T Baker - McLean HospitalAnthony King - University of MichiganIsrael Liberzon - Texas A&M Health Science CenterMike Angstadt - University of MichiganNicholas D Davenport - Minneapolis VA Health Care SystemSeth G Disner - Minneapolis VA Health Care SystemScott R Sponheim - Minneapolis VA Health Care SystemThomas Straube - University of MünsterDavid Hofmann - University of MünsterGuang Ming Lu - Nanjing UniversityRongfeng Qi - Nanjing UniversityXin Wang - University of ToledoAustin Kunch - University of ToledoHong Xie - University of ToledoYann Quidé - UNSW SydneyWissam El-Hage - Université de ToursShmuel Lissek - University of MinnesotaHannah Berg - University of MinnesotaJosh Cisler - The University of Texas at AustinMarisa Ross - Northwestern UniversityRyan J Herringa - University of Wisconsin–MadisonDaniel W Grupe - University of Wisconsin HealthJack B Nitschke - University of Wisconsin–MadisonRichard J Davidson - University of Wisconsin–MadisonChristine L Larson - University of Wisconsin–MilwaukeeTerri A deRoon-Cassini - Medical College of WisconsinCarissa W Tomas - Medical College of WisconsinJacklynn M Fitzgerald - Marquette UniversityBrandee Feola - Vanderbilt University Medical CenterJennifer Urbano-Blackford - Nebraska Medical CenterBunmi O Olatunji - Vanderbilt UniversityGeoffrey May - The University of Texas at DallasSteven M Nelson - Baylor UniversityEvan M Gordon - Washington University in St. LouisChadi G Abdallah - Baylor College of MedicineRuth Lanius - Western UniversityMaria Densmore - Western UniversityJean Théberge - Western UniversityRichard W J Neufeld - Western UniversityLee A Baugh - Sioux Falls VA Health Care SystemRaluca M Simons - University of South DakotaJeffrey S Simons - University of South DakotaVincent A Magnotta - University of IowaKelene A Fercho - University of South DakotaJeremy Elman - University of California San DiegoMatthew Panizzon - University of California San DiegoCarol Franz - University of California San DiegoMichael J Lyons - Boston UniversityWilliam Kremen - University of California San DiegoKatie A McLaughin - Harvard University PressMatthew Peverill - University of WashingtonKelly Sambrook - University of WashingtonPaul M Thompson - Marina Del Rey HospitalJennifer S Stevens - Emory UniversityRajendra A Morey - Duke UniversitySanne J H van Rooij - Emory University
- Resource Type
- Journal article
- Publication Details
- The American journal of psychiatry
- DOI
- 10.1176/appi.ajp.20250062
- PMID
- 41922983
- NLM abbreviation
- Am J Psychiatry
- ISSN
- 1535-7228
- eISSN
- 1535-7228
- Language
- English
- Electronic publication date
- 04/02/2026
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute
- Record Identifier
- 9985149576002771
Metrics
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