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. 2019 Dec 19.
doi: 10.1038/s41380-019-0631-x. Online ahead of print.

Altered White Matter Microstructural Organization in Posttraumatic Stress Disorder Across 3047 Adults: Results From the PGC-ENIGMA PTSD Consortium

Emily L Dennis  1   2   3   4 Seth G Disner  5   6 Negar Fani  7 Lauren E Salminen  8 Mark Logue  9   10   11   12 Emily K Clarke  13   14 Courtney C Haswell  13   14 Christopher L Averill  15 Lee A Baugh  16   17   18 Jessica Bomyea  19   20 Steven E Bruce  21 Jiook Cha  22   23 Kyle Choi  24 Nicholas D Davenport  5   6 Maria Densmore  25   26 Stefan du Plessis  27 Gina L Forster  16   17   28 Jessie L Frijling  29 Atilla Gonenc  30   31 Staci Gruber  30   31 Daniel W Grupe  32 Jeffrey P Guenette  33 Jasmeet Hayes  34 David Hofmann  35 Jonathan Ipser  36 Tanja Jovanovic  7   37 Sinead Kelly  38   39 Mitzy Kennis  40   41 Philipp Kinzel  38   42 Saskia B J Koch  29   43 Inga Koerte  38   42 Sheri Koopowitz  36 Mayuresh Korgaonkar  44 John Krystal  15 Lauren A M Lebois  31   45 Gen Li  46   47 Vincent A Magnotta  48 Antje Manthey  49 Geoff J May  50   51   52   53 Deleene S Menefee  54   55 Laura Nawijn  29   56 Steven M Nelson  50   51   53 Richard W J Neufeld  25   57   58   59 Jack B Nitschke  60 Daniel O'Doherty  61 Matthew Peverill  62 Kerry J Ressler  7   31   43 Annerine Roos  63 Margaret A Sheridan  64 Anika Sierk  49 Alan Simmons  19   20 Raluca M Simons  17   65 Jeffrey S Simons  18   65 Jennifer Stevens  7 Benjamin Suarez-Jimenez  22   23 Danielle R Sullivan  9   10 Jean Théberge  25   26   66 Jana K Tran  67 Leigh van den Heuvel  27 Steven J A van der Werff  68   69 Sanne J H van Rooij  7 Mirjam van Zuiden  29 Carmen Velez  70   71 Mieke Verfaellie  10   72 Robert R J M Vermeiren  68 Benjamin S C Wade  70   71   73 Tor Wager  74 Henrik Walter  49 Sherry Winternitz  31   75 Jonathan Wolff  45 Gerald York  76   77 Ye Zhu  46   47 Xi Zhu  22   23 Chadi G Abdallah  15 Richard Bryant  78 Judith K Daniels  79 Richard J Davidson  32   60   80 Kelene A Fercho  16   17   18   81 Carol Franz  20   82 Elbert Geuze  40   41 Evan M Gordon  50   51   53 Milissa L Kaufman  31   75 William S Kremen  19   20   82 Jim Lagopoulos  61 Ruth A Lanius  25   26   58 Michael J Lyons  83 Stephen R McCauley  84   85 Regina McGlinchey  31   86 Katie A McLaughlin  87 William Milberg  31   88 Yuval Neria  22   23 Miranda Olff  29   88 Soraya Seedat  63 Martha Shenton  38   89 Scott R Sponheim  5   6 Dan J Stein  36 Murray B Stein  20   90 Thomas Straube  35 David F Tate  70   71 Nic J A van der Wee  68   69 Dick J Veltman  56 Li Wang  46   47 Elisabeth A Wilde  70   85   91 Paul M Thompson  8 Peter Kochunov  92 Neda Jahanshad  8 Rajendra A Morey  13   14
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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 et al. Mol Psychiatry. .

Abstract

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.

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