Journal article
Shared and specific associations of amygdala nuclei volumes with PTSD symptom domains and childhood trauma: An ENIGMA-PGC PTSD mega-analysis
Molecular psychiatry, 42393252
07/02/2026
DOI: 10.1038/s41380-026-03718-w
PMID: 42393252
Abstract
Posttraumatic stress disorder (PTSD) is a psychiatric condition that may develop after trauma exposure. PTSD is characterized by considerable clinical heterogeneity. The amygdala's key role in fear conditioning makes it an important focus for investigating the neurobiology of PTSD. However, associations between amygdala volume and PTSD have been inconsistent. The amygdala consists of functionally distinct nuclei. Specific associations between amygdala nuclei volumes and PTSD may account for previous discrepancies between PTSD and whole amygdala volume. This study investigates the associations between amygdala nuclei volumes, PTSD diagnosis, severity, symptom cluster scores, age of onset and childhood trauma. Individuals with a PTSD diagnosis (n = 771) and controls (n = 1 081, 72% trauma-exposed) were sourced from the Enhancing Neuro-Imaging Genetics through Meta-Analysis and Psychiatric Genomics Consortium (mean age = 32.4 years, (SD = 13 years), 60% male). Nine amygdala nuclei volumes were compared to PTSD diagnosis, age of onset, overall severity, symptom cluster scores (re-experiencing, arousal, and avoidance/emotional numbing), and childhood trauma subscales. Analyses were performed using ordinary least-squares regression, corrected for age, sex, intracranial volume, and whole amygdala volume. PTSD diagnosis was not significantly associated with amygdala nuclei volumes. PTSD severity scores were associated with smaller right lateral nucleus volume (beta = -0.26, pBON = 0.01). Smaller right lateral nucleus volume was also associated with re-experiencing (beta = -1.01, pBON = 0.04) and arousal (beta = -0.9, pBON = 0.04), smaller left paralaminar nucleus volume was associated with re-experiencing (beta = -0.1, pBON = 0.04), smaller left corticoamygdaloid transition area volume was associated with avoidance (beta = -0.31, pBON = 0.02). Larger left and right central nucleus volumes were significantly associated with childhood physical abuse (beta = 0.24, pBON = 9 & times; 10-3) and neglect (beta = 0.29, pBON = 0.04), respectively. Differences in select amygdala nuclei volumes among adults are associated with PTSD severity, symptom cluster scores, and childhood physical abuse and neglect. These findings demonstrate nuclei-specific patterns consistent with their functional roles in fear learning and expression.
Details
- Title: Subtitle
- Shared and specific associations of amygdala nuclei volumes with PTSD symptom domains and childhood trauma: An ENIGMA-PGC PTSD mega-analysis
- Creators
- Mary S. Mufford - University of Cape TownDennis van der Meer - Maastricht UniversityC. Lexi Baird - Pennsylvania State UniversityDelin Sun - Duke UniversityKevin S. LaBar - Duke UniversityRaj Ramesar - Univ Cape Town, Inst Infect Dis & Mol Med, South African Med Res Council Genom & Precis Med R, Div Human Genet,Dept Pathol, Cape Town, South AfricaAhmed Hussain - Duke UniversityChadi G. Abdallah - Baylor College of MedicineElpiniki Andrew - The University of SydneyChristopher L. Averill - Yale UniversityJustin T. Baker - McLean HospitalLee A. Baugh - University of South DakotaJennifer U. Blackford - Nebraska Medical CenterJessica Bomyea - University of California San DiegoRichard A. Bryant - UNSW SydneyChristopher R. K. Ching - University of Southern CaliforniaKyle Choi - University of California San DiegoAndrew S. Cotton - University of ToledoJudith K. Daniels - University of GroningenRichard J. Davidson - University of Wisconsin–MadisonNicholas D. Davenport - Minneapolis VA Health Care SystemMichael D. De Bellis - Duke UniversityEmily L. Dennis - University of UtahMaria Densmore - Western UniversityTerri A. deRoon-Cassini - Medical College of WisconsinSeth G. Disner - Minneapolis VA Health Care SystemStefan du Plessis - Stellenbosch UniversityAmit Etkin - Alto Neuroscience (United States)Negar Fani - Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USAKelene A. Fercho - University of South DakotaJacklynn Fitzgerald - Marquette UniversityElbert Geuze - University Medical Center UtrechtEvan M. Gordon - Baylor UniversityDaniel W. Grupe - University of Wisconsin–MadisonIlan Harpaz-Rotem - National Center for PTSDCourtney C. Russel - Duke UniversityJulia I. Herzog - Central Institute of Mental HealthDavid Hofmann - University of MünsterAnna R. Hudson - Ghent UniversityJonathan Ipser - University of Cape TownNeda Jahanshad - University of Southern CaliforniaTanja Jovanovic - Wayne State UniversityMilissa L. Kaufman - McLean HospitalSaskia B. J. Koch - Radboud University NijmegenInga K. Koerte - Brigham and Women's HospitalMayuresh S. Korgaonkar - Westmead Institute for Medical ResearchJohn H. Krystal - Yale UniversityRuth Lanius - University of LondonChristine Larson - University of Wisconsin–MilwaukeeLauren A. M. Lebois - McLean HospitalIfat Levy - National Center for PTSDGen Li - Chinese Academy of SciencesIsrael Liberzon - University of MichiganMark W. Logue - Boston UniversityVincent A. Magnotta - University of Iowa, Iowa Neuroscience InstituteAntje Manthey - Charité - Universitätsmedizin BerlinAdi Maron-Katz - Stanford UniversityGeoffrey May - The University of Texas at DallasKatie A. McLaughlin - Harvard UniversitySven C. Mueller - Universidad de DeustoLaura Nawijn - Amsterdam University Medical CentersSteven M. Nelson - University of MinnesotaYuval Neria - Columbia University Irving Medical CenterRichard W. J. Neufeld - Western UniversityJack B. Nitschke - University of Wisconsin–MadisonErin N. O'Leary - University of ToledoBunmi O. Olatunji - Vanderbilt UniversityMiranda Olff - Amsterdam University Medical CentersElizabeth A. Olson - Harvard UniversityMatthew Peverill - Univ Wisconsin Madison, Dept Psychiat, Madison, WI USAK. Luan Phan - The Ohio State UniversityEvelyn Pineda - University of Rochester Medical CenterKerry J. Ressler - McLean HospitalIsabelle M. Rosso - McLean HospitalLauren E. Salminen - Marina Del Rey HospitalKelly Meltzer - University of WashingtonChristian Schmahl - Central Institute of Mental HealthSoraya Seedat - Stellenbosch UniversityCaitlin A. Sharp - University of Rochester Medical CenterMartha E. Shenton - Brigham and Women's HospitalAnika Sierk - Univ Med Ctr Charite, Dept Psychiat & Psychotherapy, Berlin, GermanyRaluca M. Simons - University of South DakotaJeffrey S. Simons - University of South DakotaScott R. Sponheim - University of MinnesotaMurray B. Stein - University of California San DiegoJennifer S. Stevens - Emory University School of MedicineThomas Straube - University of MünsterBenjamin Suarez-Jimenez - University of RochesterJean Theberge - University of LondonSophia I. Thomopolous - Univ Southern Calif, Imaging Genet Ctr, Mark & Mary Stevens Neuroimaging & Informat Inst, Keck Sch Med USC, Marina Del Rey, CA 90292 USANic J. A. van der Wee - Leiden University Medical CenterSteven J. A. van der Werff - Leiden University Medical CenterTheo G. M. van Erp - University of California, IrvineSanne J. H. van Rooij - Emory University School of MedicineMirjam van Zuiden - Amsterdam University Medical CentersDick J. Veltman - Amsterdam University Medical CentersRobert R. J. M. Vermeiren - Leiden Univ, Med Ctr, Dept Psychiat & Psychol, Leiden, NetherlandsHenrik Walter - Charité - Universitätsmedizin BerlinXin Wang - University of Iowa, Psychological and Brain SciencesLi Wang - Chinese Academy of SciencesHong Xie - University of ToledoXi Zhu - Columbia University Irving Medical CenterYe Zhu - Institute of MechanicsPaul M. Thompson - University of Southern CaliforniaOle A. Andreassen - University of OsloDan J. Stein - South African Medical Research CouncilRajendra A. Morey - Duke UniversityShareefa Dalvie - University of Cape Town
- Resource Type
- Journal article
- Publication Details
- Molecular psychiatry, 42393252
- DOI
- 10.1038/s41380-026-03718-w
- PMID
- 42393252
- NLM abbreviation
- Mol Psychiatry
- ISSN
- 1359-4184
- eISSN
- 1476-5578
- Publisher
- Springer Nature
- Number of pages
- 10
- Grant note
- MH096987, MH120400 MH111671-01A1 U.S. Department of Veterans Affairs, National Center for PTSD; US Department of Veterans Affairs NordForsk R01MH133840 KG Jebsen Foundation, EU Psych-Strata and environMENTAL VA Mid-Atlantic MIRECC; R01 MH111671, R01 MH 129832, R01 MH139648, K24MH71434 & K24 DA028773 (MDDB), R01 MH63407 (MDDB), R01 AA12479 (MDDB), R01 MH61744 (MDDB) Norges Forskningsrd (Research Council of Norway); Research Council of Norway Children's Early Intervention Trust (Ymddiriedolaeth Ymyrraeth Cynnar Plant)
- Language
- English
- Electronic publication date
- 07/02/2026
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute
- Record Identifier
- 9985179235202771
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