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<p>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 (<i>n</i> = 771) and controls (<i>n</i> = 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 (β = −0.26, p<sub>BON</sub> = 0.01). Smaller right lateral nucleus volume was also associated with re-experiencing (β = −1.01, p<sub>BON</sub> = 0.04) and arousal (β = −0.9, p<sub>BON</sub> = 0.04), smaller left paralaminar nucleus volume was associated with re-experiencing (β = −0.1, p<sub>BON</sub> = 0.04), smaller left corticoamygdaloid transition area volume was associated with avoidance (β = −0.31, p<sub>BON</sub> = 0.02). Larger left and right central nucleus volumes were significantly associated with childhood physical abuse (β = 0.24, p<sub>BON</sub> = 9 × 10<sup>−3</sup>) and neglect (β = 0.29, p<sub>BON</sub> = 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.</p>

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Shared and specific associations of amygdala nuclei volumes with PTSD symptom domains and childhood trauma: An ENIGMA-PGC PTSD mega-analysis

  • 期刊论文

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  • 发表日期：

    2026年7月2日

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  • Mary S. Mufford,
  • Dennis van der Meer,
  • C. Lexi Baird,
  • Delin Sun,
  • Kevin S. LaBar,
  • Raj Ramesar,
  • Ahmed Hussain,
  • Chadi G. Abdallah,
  • Elpiniki Andrew,
  • Christopher L. Averill,
  • Justin T. Baker,
  • Lee A. Baugh,
  • Jennifer U. Blackford,
  • Jessica Bomyea,
  • Richard A. Bryant,
  • Christopher R. K. Ching,
  • Kyle Choi,
  • Andrew S. Cotton,
  • Judith K. Daniels,
  • Nicholas D. Davenport,
  • Richard J. Davidson,
  • Michael D. De Bellis,
  • Emily L. Dennis,
  • Maria Densmore,
  • Terri A. deRoon-Cassini,
  • Seth G. Disner,
  • Stefan du Plessis,
  • Amit Etkin,
  • Negar Fani,
  • Kelene A. Fercho,
  • Jacklynn Fitzgerald,
  • Elbert Geuze,
  • Evan M. Gordon,
  • Daniel W. Grupe,
  • Ilan Harpaz-Rotem,
  • Courtney C. Russel,
  • Julia I. Herzog,
  • David Hofmann,
  • Anna R. Hudson,
  • Jonathan Ipser,
  • Neda Jahanshad,
  • Tanja Jovanovic,
  • Milissa L. Kaufman,
  • Saskia B. J. Koch,
  • Inga K. Koerte,
  • Mayuresh S. Korgaonkar,
  • John H. Krystal,
  • Ruth Lanius,
  • Christine Larson,
  • Lauren A. M. Lebois,
  • Ifat Levy,
  • Gen Li,
  • Israel Liberzon,
  • Mark W. Logue,
  • Vincent A. Magnotta,
  • Antje Manthey,
  • Adi Maron-Katz,
  • Geoffrey May,
  • Katie A. McLaughlin,
  • Sven C. Mueller,
  • Laura Nawijn,
  • Steven M. Nelson,
  • Yuval Neria,
  • Richard W. J. Neufeld,
  • Jack B. Nitschke,
  • Erin N. O’Leary,
  • Bunmi O. Olatunji,
  • Miranda Olff,
  • Elizabeth A. Olson,
  • Matthew Peverill,
  • K. Luan Phan,
  • Evelyn Pineda,
  • Kerry J. Ressler,
  • Isabelle M. Rosso,
  • Lauren E. Salminen,
  • Kelly Meltzer,
  • Christian Schmahl,
  • Soraya Seedat,
  • Caitlin A. Sharp,
  • Martha E. Shenton,
  • Anika Sierk,
  • Raluca M. Simons,
  • Jeffrey S. Simons,
  • Scott R. Sponheim,
  • Murray B. Stein,
  • Jennifer S. Stevens,
  • Thomas Straube,
  • Benjamin Suarez-Jimenez,
  • Jean Théberge,
  • Sophia I. Thomopolous,
  • Nic J. A. van der Wee,
  • Steven J. A. van der Werff,
  • Theo G. M. van Erp,
  • Sanne J. H. van Rooij,
  • Mirjam van Zuiden,
  • Dick J. Veltman,
  • Robert R. J. M. Vermeiren,
  • Henrik Walter,
  • Xin Wang,
  • Li Wang,
  • Hong Xie,
  • Xi Zhu,
  • Ye Zhu,
  • Paul M. Thompson,
  • Ole A. Andreassen,
  • Dan J. Stein,
  • Rajendra A. Morey,
  • Shareefa Dalvie

摘要

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 (β = −0.26, pBON = 0.01). Smaller right lateral nucleus volume was also associated with re-experiencing (β = −1.01, pBON = 0.04) and arousal (β = −0.9, pBON = 0.04), smaller left paralaminar nucleus volume was associated with re-experiencing (β = −0.1, pBON = 0.04), smaller left corticoamygdaloid transition area volume was associated with avoidance (β = −0.31, pBON = 0.02). Larger left and right central nucleus volumes were significantly associated with childhood physical abuse (β = 0.24, pBON = 9 × 10−3) and neglect (β = 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.