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Altered white matter microstructural organization in posttraumatic stress disorder across 3047 adults: results from the PGC-ENIGMA PTSD consortium.

Emily L Dennis | Seth G Disner | Negar Fani | Lauren E Salminen | Mark Logue | Emily K Clarke | Courtney C Haswell | Christopher L Averill | Lee A Baugh | Jessica Bomyea | Steven E Bruce | Jiook Cha | Kyle Choi | Nicholas D Davenport | Maria Densmore | Stefan du Plessis | Gina L Forster | Jessie L Frijling | Atilla Gonenc | Staci Gruber | Daniel W Grupe | Jeffrey P Guenette | Jasmeet Hayes | David Hofmann | Jonathan Ipser | Tanja Jovanovic | Sinead Kelly | Mitzy Kennis | Philipp Kinzel | Saskia B J Koch | Inga Koerte | Sheri Koopowitz | Mayuresh Korgaonkar | John Krystal | Lauren A M Lebois | Gen Li | Vincent A Magnotta | Antje Manthey | Geoff J May | Deleene S Menefee | Laura Nawijn | Steven M Nelson | Richard W J Neufeld | Jack B Nitschke | Daniel O'Doherty | Matthew Peverill | Kerry J Ressler | Annerine Roos | Margaret A Sheridan | Anika Sierk | Alan Simmons | Raluca M Simons | Jeffrey S Simons | Jennifer Stevens | Benjamin Suarez-Jimenez | Danielle R Sullivan | Jean Théberge | Jana K Tran | Leigh van den Heuvel | Steven J A van der Werff | Sanne J H van Rooij | Mirjam van Zuiden | Carmen Velez | Mieke Verfaellie | Robert R J M Vermeiren | Benjamin S C Wade | Tor Wager | Henrik Walter | Sherry Winternitz | Jonathan Wolff | Gerald York | Ye Zhu | Xi Zhu | Chadi G Abdallah | Richard Bryant | Judith K Daniels | Richard J Davidson | Kelene A Fercho | Carol Franz | Elbert Geuze | Evan M Gordon | Milissa L Kaufman | William S Kremen | Jim Lagopoulos | Ruth A Lanius | Michael J Lyons | Stephen R McCauley | Regina McGlinchey | Katie A McLaughlin | William Milberg | Yuval Neria | Miranda Olff | Soraya Seedat | Martha Shenton | Scott R Sponheim | Dan J Stein | Murray B Stein | Thomas Straube | David F Tate | Nic J A van der Wee | Dick J Veltman | Li Wang | Elisabeth A Wilde | Paul M Thompson | Peter Kochunov | Neda Jahanshad | Rajendra A Morey
Molecular psychiatry | 2021

A growing number of studies have examined alterations in white matter organization in people with posttraumatic stress disorder (PTSD) using diffusion MRI (dMRI), but the results have been mixed which may be partially due to relatively small sample sizes among studies. Altered structural connectivity may be both a neurobiological vulnerability for, and a result of, PTSD. In an effort to find reliable effects, we present a multi-cohort analysis of dMRI metrics across 3047 individuals from 28 cohorts currently participating in the PGC-ENIGMA PTSD working group (a joint partnership between the Psychiatric Genomics Consortium and the Enhancing NeuroImaging Genetics through Meta-Analysis consortium). Comparing regional white matter metrics across the full brain in 1426 individuals with PTSD and 1621 controls (2174 males/873 females) between ages 18-83, 92% of whom were trauma-exposed, we report associations between PTSD and disrupted white matter organization measured by lower fractional anisotropy (FA) in the tapetum region of the corpus callosum (Cohen's d = -0.11, p = 0.0055). The tapetum connects the left and right hippocampus, for which structure and function have been consistently implicated in PTSD. Results were consistent even after accounting for the effects of multiple potentially confounding variables: childhood trauma exposure, comorbid depression, history of traumatic brain injury, current alcohol abuse or dependence, and current use of psychotropic medications. Our results show that PTSD may be associated with alterations in the broader hippocampal network.

Pubmed ID: 31857689

Research resources used in this publication

None found

Antibodies used in this publication

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Associated grants

  • Agency: NIDA NIH HHS, United States
    Id: R01 DA035484
  • Agency: NIMH NIH HHS, United States
    Id: F32 MH109274
  • Agency: NIBIB NIH HHS, United States
    Id: R01 EB015611
  • Agency: CSRD VA, United States
    Id: I01 CX000715
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH116147
  • Agency: CSRD VA, United States
    Id: I01 CX001542
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH119227
  • Agency: NIMH NIH HHS, United States
    Id: T32 MH018931
  • Agency: NIH HHS, United States
    Id: S10 OD023696
  • Agency: NIMH NIH HHS, United States
    Id: K01 MH118467
  • Agency: RRD VA, United States
    Id: IK2 RX000709
  • Agency: NIBIB NIH HHS, United States
    Id: P41 EB015922
  • Agency: NIAID NIH HHS, United States
    Id: R38 AI140299
  • Agency: NICHD NIH HHS, United States
    Id: P30 HD003352
  • Agency: NIMH NIH HHS, United States
    Id: R56 MH071537
  • Agency: NIA NIH HHS, United States
    Id: R01 AG058822
  • Agency: RRD VA, United States
    Id: IK2 RX002922
  • Agency: NIMH NIH HHS, United States
    Id: R21 MH098212
  • Agency: NICHD NIH HHS, United States
    Id: K12 HD085850
  • Agency: NIA NIH HHS, United States
    Id: U54 AG062334
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH071537
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH117292
  • Agency: CSRD VA, United States
    Id: IK2 CX001680
  • Agency: NCATS NIH HHS, United States
    Id: UL1 TR001863
  • Agency: NIMH NIH HHS, United States
    Id: R21 MH112956
  • Agency: NIMH NIH HHS, United States
    Id: K01 MH118428
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH105355
  • Agency: NCRR NIH HHS, United States
    Id: M01 RR000039
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH111671
  • Agency: NINDS NIH HHS, United States
    Id: K99 NS096116
  • Agency: RRD VA, United States
    Id: IK1 RX002325
  • Agency: RRD VA, United States
    Id: I01 RX000622
  • Agency: NIBIB NIH HHS, United States
    Id: U54 EB020403
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH117601
  • Agency: NCATS NIH HHS, United States
    Id: UL1 TR000454
  • Agency: NIA NIH HHS, United States
    Id: R56 AG058854
  • Agency: NIMH NIH HHS, United States
    Id: K23 MH101380
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH043454
  • Agency: NIMH NIH HHS, United States
    Id: K01 MH109836
  • Agency: CSRD VA, United States
    Id: IK2 CX001772
  • Agency: NIMH NIH HHS, United States
    Id: K23 MH101498
  • Agency: NICHD NIH HHS, United States
    Id: R01 HD071982
  • Agency: NIMH NIH HHS, United States
    Id: K23 MH090366
  • Agency: NIA NIH HHS, United States
    Id: R01 AG022381
  • Agency: NIA NIH HHS, United States
    Id: R01 AG050595
  • Agency: NIA NIH HHS, United States
    Id: R01 AG059874

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NeuroImaging Tools and Resources Collaboratory (NITRC) (tool)

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Software repository for comparing structural (MRI) and functional neuroimaging (fMRI, PET, EEG, MEG) software tools and resources. NITRC collects and points to standardized information about structural or functional neuroimaging tool or resource.

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ENIGMA-DTI Pipeline (tool)

RRID:SCR_014649

Pipeline which provides tools to extract whole-brain average and regional measurements from DTI images including FA, AD, RD and MD. Protocols for preprocessing, ENIGMA-DTI processing (skeletonization and ROI extraction), and GWAS analysis are available. Software tools used for each process are listed within the protocols.

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