Resting-State Functional Connectivity of the Amygdala and Hippocampus in PTSD: Results From the PGC-ENIGMA PTSD Working Group

Cecilia A Hinojosa; Delin Sun; Courtney Russell; C Lexi Baird; Ahmed Hussain; Mohammad Sendi; Neda Jahanshad; Lauren E Salminen; Miranda Olff; Jessie L Frijling; Dick J Veltman; Saskia B J Koch; Laura Nawijn; Mirjam van Zuiden; Li Wang; Ye Zhu; Gen Li; Dan J Stein; Jonathan Ipser; Sheri-Michelle Koopowitz; Yuval Neria; Xi Zhu; Orren Ravid; Sigal Zilcha-Mano; Amit Lazarov; Benjamin Suarez-Jimenez; Ashley A Huggins; Kerry Ressler; Tanja Jovanovic; Negar Fani; Sven C Mueller; Anna R Hudson; Judith K Daniels; Anika Sierk; Antje Manthey; Henrik Walter; Nic J A van der Wee; Steven J A van der Werff; Robert R J M Vermeiren; Ivan Rektor; Pavel Říha; Milissa L Kaufman; Lauren A M Lebois; Justin T Baker; Anthony King; Israel Liberzon; Mike Angstadt; Nicholas D Davenport; Seth G Disner; Scott R Sponheim; Thomas Straube; David Hofmann; Guang Ming Lu; Rongfeng Qi; Xin Wang; Austin Kunch; Hong Xie; Yann Quidé; Wissam El-Hage; Shmuel Lissek; Hannah Berg; Josh Cisler; Marisa Ross; Ryan J Herringa; Daniel W Grupe; Jack B Nitschke; Richard J Davidson; Christine L Larson; Terri A deRoon-Cassini; Carissa W Tomas; Jacklynn M Fitzgerald; Brandee Feola; Jennifer Urbano-Blackford; Bunmi O Olatunji; Geoffrey May; Steven M Nelson; Evan M Gordon; Chadi G Abdallah; Ruth Lanius; Maria Densmore; Jean Théberge; Richard W J Neufeld; Lee A Baugh; Raluca M Simons; Jeffrey S Simons; Vincent A Magnotta; Kelene A Fercho; Jeremy Elman; Matthew Panizzon; Carol Franz; Michael J Lyons; William Kremen; Katie A McLaughin; Matthew Peverill; Kelly Sambrook; Paul M Thompson; Jennifer S Stevens; Rajendra A Morey; Sanne J H van Rooij

doi:10.1176/appi.ajp.20250062

Resting-State Functional Connectivity of the Amygdala and Hippocampus in PTSD: Results From the PGC-ENIGMA PTSD Working Group

Cecilia A Hinojosa^*
, Delin Sun
, Courtney Russell
, C Lexi Baird
, Ahmed Hussain
, Mohammad Sendi
, Neda Jahanshad
, Lauren E Salminen
, Miranda Olff
, Jessie L Frijling
, Dick J Veltman
, Saskia B J Koch
, Laura Nawijn
, Mirjam van Zuiden
, Li Wang
, Ye Zhu
, Gen Li
, Dan J Stein
, Jonathan Ipser
, Sheri-Michelle Koopowitz

Yuval Neria, Xi Zhu, Orren Ravid, Sigal Zilcha-Mano, Amit Lazarov, Benjamin Suarez-Jimenez, Ashley A Huggins, Kerry Ressler, Tanja Jovanovic, Negar Fani, Sven C Mueller, Anna R Hudson, Judith K Daniels, Anika Sierk, Antje Manthey, Henrik Walter, Nic J A van der Wee, Steven J A van der Werff, Robert R J M Vermeiren, Ivan Rektor, Pavel Říha, Milissa L Kaufman, Lauren A M Lebois, Justin T Baker, Anthony King, Israel Liberzon, Mike Angstadt, Nicholas D Davenport, Seth G Disner, Scott R Sponheim, Thomas Straube, David Hofmann, Guang Ming Lu, Rongfeng Qi, Xin Wang, Austin Kunch, Hong Xie, Yann Quidé, Wissam El-Hage, Shmuel Lissek, Hannah Berg, Josh Cisler, Marisa Ross, Ryan J Herringa, Daniel W Grupe, Jack B Nitschke, Richard J Davidson, Christine L Larson, Terri A deRoon-Cassini, Carissa W Tomas, Jacklynn M Fitzgerald, Brandee Feola, Jennifer Urbano-Blackford, Bunmi O Olatunji, Geoffrey May, Steven M Nelson, Evan M Gordon, Chadi G Abdallah, Ruth Lanius, Maria Densmore, Jean Théberge, Richard W J Neufeld, Lee A Baugh, Raluca M Simons, Jeffrey S Simons, Vincent A Magnotta, Kelene A Fercho, Jeremy Elman, Matthew Panizzon, Carol Franz, Michael J Lyons, William Kremen, Katie A McLaughin, Matthew Peverill, Kelly Sambrook, Paul M Thompson, Jennifer S Stevens, Rajendra A Morey, Sanne J H van Rooij

^*Corresponding author for this work

Chair Engelhard

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
Duke University
McLean Hospital/Harvard Medical School
Mark and Mary Stevens Neuroimaging and Informatics Institute
Amsterdam UMC University of Amsterdam
University of Chinese Academy of Sciences
University of Cape Town
Columbia University Medical Center
New York State Psychiatric Institute
University of Haifa
University of Rochester Medical Center
University of Arizona
Ghent University
University of Groningen
University Medical Center Charité
Leiden University Medical Center
Masaryk University
Harvard Medical School
University of Michigan-Dearborn
University of North Texas Health Science Center
Minneapolis VA Health Care System
University of Münster
Medical School of Nanjing University
University of Toledo
University of New South Wales
iBraiN
University of Minnesota Rochester
University of Texas at Austin
Northwestern University Institute for Policy Research
University of Wisconsin-Madison
University of Wisconsin-Milwaukee
Medical College of Wisconsin
Marquette University
Vanderbilt University
University of Texas at Dallas
Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Baylor College of Medicine
Western University
University of South Dakota
Sioux Falls VA Health Care System
University of Iowa
University of California at San Diego
University of Southern California
Boston University
Harvard University
University of Washington

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Journal	American Journal of Psychiatry
DOIs	https://doi.org/10.1176/appi.ajp.20250062
Publication status	E-pub ahead of print - 2 Apr 2026

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10.1176/appi.ajp.20250062

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Hinojosa, C. A., Sun, D., Russell, C., Baird, C. L., Hussain, A., Sendi, M., Jahanshad, N., Salminen, L. E., Olff, M., Frijling, J. L., Veltman, D. J., Koch, S. B. J., Nawijn, L., van Zuiden, M., Wang, L., Zhu, Y., Li, G., Stein, D. J., Ipser, J., ... van Rooij, S. J. H. (2026). Resting-State Functional Connectivity of the Amygdala and Hippocampus in PTSD: Results From the PGC-ENIGMA PTSD Working Group. American Journal of Psychiatry. Advance online publication. https://doi.org/10.1176/appi.ajp.20250062

@article{ab40f001d6b94eeab7b867ee0551d1be,

title = "Resting-State Functional Connectivity of the Amygdala and Hippocampus in PTSD: Results From the PGC-ENIGMA PTSD Working Group",

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.",

author = "Hinojosa, \{Cecilia A\} and Delin Sun and Courtney Russell and Baird, \{C Lexi\} and Ahmed Hussain and Mohammad Sendi and Neda Jahanshad and Salminen, \{Lauren E\} and Miranda Olff and Frijling, \{Jessie L\} and Veltman, \{Dick J\} and Koch, \{Saskia B J\} and Laura Nawijn and \{van Zuiden\}, Mirjam and Li Wang and Ye Zhu and Gen Li and Stein, \{Dan J\} and Jonathan Ipser and Sheri-Michelle Koopowitz and Yuval Neria and Xi Zhu and Orren Ravid and Sigal Zilcha-Mano and Amit Lazarov and Benjamin Suarez-Jimenez and Huggins, \{Ashley A\} and Kerry Ressler and Tanja Jovanovic and Negar Fani and Mueller, \{Sven C\} and Hudson, \{Anna R\} and Daniels, \{Judith K\} and Anika Sierk and Antje Manthey and Henrik Walter and \{van der Wee\}, \{Nic J A\} and \{van der Werff\}, \{Steven J A\} and Vermeiren, \{Robert R J M\} and Ivan Rektor and Pavel {\v R}{\'i}ha and Kaufman, \{Milissa L\} and Lebois, \{Lauren A M\} and Baker, \{Justin T\} and Anthony King and Israel Liberzon and Mike Angstadt and Davenport, \{Nicholas D\} and Disner, \{Seth G\} and Sponheim, \{Scott R\} and Thomas Straube and David Hofmann and Lu, \{Guang Ming\} and Rongfeng Qi and Xin Wang and Austin Kunch and Hong Xie and Yann Quid{\'e} and Wissam El-Hage and Shmuel Lissek and Hannah Berg and Josh Cisler and Marisa Ross and Herringa, \{Ryan J\} and Grupe, \{Daniel W\} and Nitschke, \{Jack B\} and Davidson, \{Richard J\} and Larson, \{Christine L\} and deRoon-Cassini, \{Terri A\} and Tomas, \{Carissa W\} and Fitzgerald, \{Jacklynn M\} and Brandee Feola and Jennifer Urbano-Blackford and Olatunji, \{Bunmi O\} and Geoffrey May and Nelson, \{Steven M\} and Gordon, \{Evan M\} and Abdallah, \{Chadi G\} and Ruth Lanius and Maria Densmore and Jean Th{\'e}berge and Neufeld, \{Richard W J\} and Baugh, \{Lee A\} and Simons, \{Raluca M\} and Simons, \{Jeffrey S\} and Magnotta, \{Vincent A\} and Fercho, \{Kelene A\} and Jeremy Elman and Matthew Panizzon and Carol Franz and Lyons, \{Michael J\} and William Kremen and McLaughin, \{Katie A\} and Matthew Peverill and Kelly Sambrook and Thompson, \{Paul M\} and Stevens, \{Jennifer S\} and Morey, \{Rajendra A\} and \{van Rooij\}, \{Sanne J H\}",

year = "2026",

month = apr,

day = "2",

doi = "10.1176/appi.ajp.20250062",

language = "English",

journal = "American Journal of Psychiatry",

issn = "0002-953X",

publisher = "American Psychiatric Association",

}

Hinojosa, CA, Sun, D, Russell, C, Baird, CL, Hussain, A, Sendi, M, Jahanshad, N, Salminen, LE, Olff, M, Frijling, JL, Veltman, DJ, Koch, SBJ, Nawijn, L, van Zuiden, M, Wang, L, Zhu, Y, Li, G, Stein, DJ, Ipser, J, Koopowitz, S-M, Neria, Y, Zhu, X, Ravid, O, Zilcha-Mano, S, Lazarov, A, Suarez-Jimenez, B, Huggins, AA, Ressler, K, Jovanovic, T, Fani, N, Mueller, SC, Hudson, AR, Daniels, JK, Sierk, A, Manthey, A, Walter, H, van der Wee, NJA, van der Werff, SJA, Vermeiren, RRJM, Rektor, I, Říha, P, Kaufman, ML, Lebois, LAM, Baker, JT, King, A, Liberzon, I, Angstadt, M, Davenport, ND, Disner, SG, Sponheim, SR, Straube, T, Hofmann, D, Lu, GM, Qi, R, Wang, X, Kunch, A, Xie, H, Quidé, Y, El-Hage, W, Lissek, S, Berg, H, Cisler, J, Ross, M, Herringa, RJ, Grupe, DW, Nitschke, JB, Davidson, RJ, Larson, CL, deRoon-Cassini, TA, Tomas, CW, Fitzgerald, JM, Feola, B, Urbano-Blackford, J, Olatunji, BO, May, G, Nelson, SM, Gordon, EM, Abdallah, CG, Lanius, R, Densmore, M, Théberge, J, Neufeld, RWJ, Baugh, LA, Simons, RM, Simons, JS, Magnotta, VA, Fercho, KA, Elman, J, Panizzon, M, Franz, C, Lyons, MJ, Kremen, W, McLaughin, KA, Peverill, M, Sambrook, K, Thompson, PM, Stevens, JS, Morey, RA & van Rooij, SJH 2026, 'Resting-State Functional Connectivity of the Amygdala and Hippocampus in PTSD: Results From the PGC-ENIGMA PTSD Working Group', American Journal of Psychiatry. https://doi.org/10.1176/appi.ajp.20250062

TY - JOUR

T1 - Resting-State Functional Connectivity of the Amygdala and Hippocampus in PTSD

T2 - Results From the PGC-ENIGMA PTSD Working Group

AU - Hinojosa, Cecilia A

AU - Sun, Delin

AU - Russell, Courtney

AU - Baird, C Lexi

AU - Hussain, Ahmed

AU - Sendi, Mohammad

AU - Jahanshad, Neda

AU - Salminen, Lauren E

AU - Olff, Miranda

AU - Frijling, Jessie L

AU - Veltman, Dick J

AU - Koch, Saskia B J

AU - Nawijn, Laura

AU - van Zuiden, Mirjam

AU - Wang, Li

AU - Zhu, Ye

AU - Li, Gen

AU - Stein, Dan J

AU - Ipser, Jonathan

AU - Koopowitz, Sheri-Michelle

AU - Neria, Yuval

AU - Zhu, Xi

AU - Ravid, Orren

AU - Zilcha-Mano, Sigal

AU - Lazarov, Amit

AU - Suarez-Jimenez, Benjamin

AU - Huggins, Ashley A

AU - Ressler, Kerry

AU - Jovanovic, Tanja

AU - Fani, Negar

AU - Mueller, Sven C

AU - Hudson, Anna R

AU - Daniels, Judith K

AU - Sierk, Anika

AU - Manthey, Antje

AU - Walter, Henrik

AU - van der Wee, Nic J A

AU - van der Werff, Steven J A

AU - Vermeiren, Robert R J M

AU - Rektor, Ivan

AU - Říha, Pavel

AU - Kaufman, Milissa L

AU - Lebois, Lauren A M

AU - Baker, Justin T

AU - King, Anthony

AU - Liberzon, Israel

AU - Angstadt, Mike

AU - Davenport, Nicholas D

AU - Disner, Seth G

AU - Sponheim, Scott R

AU - Straube, Thomas

AU - Hofmann, David

AU - Lu, Guang Ming

AU - Qi, Rongfeng

AU - Wang, Xin

AU - Kunch, Austin

AU - Xie, Hong

AU - Quidé, Yann

AU - El-Hage, Wissam

AU - Lissek, Shmuel

AU - Berg, Hannah

AU - Cisler, Josh

AU - Ross, Marisa

AU - Herringa, Ryan J

AU - Grupe, Daniel W

AU - Nitschke, Jack B

AU - Davidson, Richard J

AU - Larson, Christine L

AU - deRoon-Cassini, Terri A

AU - Tomas, Carissa W

AU - Fitzgerald, Jacklynn M

AU - Feola, Brandee

AU - Urbano-Blackford, Jennifer

AU - Olatunji, Bunmi O

AU - May, Geoffrey

AU - Nelson, Steven M

AU - Gordon, Evan M

AU - Abdallah, Chadi G

AU - Lanius, Ruth

AU - Densmore, Maria

AU - Théberge, Jean

AU - Neufeld, Richard W J

AU - Baugh, Lee A

AU - Simons, Raluca M

AU - Simons, Jeffrey S

AU - Magnotta, Vincent A

AU - Fercho, Kelene A

AU - Elman, Jeremy

AU - Panizzon, Matthew

AU - Franz, Carol

AU - Lyons, Michael J

AU - Kremen, William

AU - McLaughin, Katie A

AU - Peverill, Matthew

AU - Sambrook, Kelly

AU - Thompson, Paul M

AU - Stevens, Jennifer S

AU - Morey, Rajendra A

AU - van Rooij, Sanne J H

PY - 2026/4/2

Y1 - 2026/4/2

N2 - 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.

AB - 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.

U2 - 10.1176/appi.ajp.20250062

DO - 10.1176/appi.ajp.20250062

M3 - Article

C2 - 41922983

SN - 0002-953X

JO - American Journal of Psychiatry

JF - American Journal of Psychiatry

ER -

Resting-State Functional Connectivity of the Amygdala and Hippocampus in PTSD: Results From the PGC-ENIGMA PTSD Working Group

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