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

Journal articles  - Journal Article
Hinojosa, CA; Sun, D; Russell, C; Baird, CL; Hussain, A; Sendi, M; Jahanshad, N; Salminen, LE; Olff, M; Frijling, JL; Veltman, DJ; Koch, SBJ ...
Published in: Am J Psychiatry
May 1, 2026

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.

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Published In

Am J Psychiatry

DOI

EISSN

1535-7228

Publication Date

May 1, 2026

Volume

183

Issue

5

Start / End Page

333 / 342

Location

United States

Related Subject Headings

  • Stress Disorders, Post-Traumatic
  • Psychiatry
  • Neural Pathways
  • Middle Aged
  • Male
  • Magnetic Resonance Imaging
  • Humans
  • Hippocampus
  • Female
  • Connectome
 

Citation

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Chicago
ICMJE
MLA
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Hinojosa, C. A., Sun, D., Russell, C., Baird, C. L., Hussain, A., Sendi, M., … 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. Am J Psychiatry, 183(5), 333–342. https://doi.org/10.1176/appi.ajp.20250062
Hinojosa, Cecilia A., Delin Sun, Courtney Russell, C Lexi Baird, Ahmed Hussain, Mohammad Sendi, Neda Jahanshad, et al. “Resting-State Functional Connectivity of the Amygdala and Hippocampus in PTSD: Results From the PGC-ENIGMA PTSD Working Group.” Am J Psychiatry 183, no. 5 (May 1, 2026): 333–42. https://doi.org/10.1176/appi.ajp.20250062.
Hinojosa CA, Sun D, Russell C, Baird CL, Hussain A, Sendi M, et al. Resting-State Functional Connectivity of the Amygdala and Hippocampus in PTSD: Results From the PGC-ENIGMA PTSD Working Group. Am J Psychiatry. 2026 May 1;183(5):333–42.
Hinojosa, Cecilia A., et al. “Resting-State Functional Connectivity of the Amygdala and Hippocampus in PTSD: Results From the PGC-ENIGMA PTSD Working Group.” Am J Psychiatry, vol. 183, no. 5, May 2026, pp. 333–42. Pubmed, doi:10.1176/appi.ajp.20250062.
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. Resting-State Functional Connectivity of the Amygdala and Hippocampus in PTSD: Results From the PGC-ENIGMA PTSD Working Group. Am J Psychiatry. 2026 May 1;183(5):333–342.
Journal cover image

Published In

Am J Psychiatry

DOI

EISSN

1535-7228

Publication Date

May 1, 2026

Volume

183

Issue

5

Start / End Page

333 / 342

Location

United States

Related Subject Headings

  • Stress Disorders, Post-Traumatic
  • Psychiatry
  • Neural Pathways
  • Middle Aged
  • Male
  • Magnetic Resonance Imaging
  • Humans
  • Hippocampus
  • Female
  • Connectome