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

doi:10.1038/s41380-019-0631-x

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 GruberDaniel 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

Great Plains IDeA-CTR

Research output: Contribution to journal › Article › peer-review

29 Scopus citations

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.

Original language	English (US)
Pages (from-to)	4315-4330
Number of pages	16
Journal	Molecular Psychiatry
Volume	26
Issue number	8
DOIs	https://doi.org/10.1038/s41380-019-0631-x
State	Published - Aug 2021

ASJC Scopus subject areas

Molecular Biology
Psychiatry and Mental health
Cellular and Molecular Neuroscience

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10.1038/s41380-019-0631-x

Cite this

Dennis, E. L., Disner, S. G., Fani, N., Salminen, L. E., Logue, M., Clarke, E. K., Haswell, C. C., Averill, C. L., Baugh, L. A., Bomyea, J., Bruce, S. E., Cha, J., Choi, K., Davenport, N. D., Densmore, M., du Plessis, S., Forster, G. L., Frijling, J. L., Gonenc, A., ... Morey, R. A. (2021). Altered white matter microstructural organization in posttraumatic stress disorder across 3047 adults: results from the PGC-ENIGMA PTSD consortium. Molecular Psychiatry, 26(8), 4315-4330. https://doi.org/10.1038/s41380-019-0631-x

Dennis, EL, Disner, SG, Fani, N, Salminen, LE, Logue, M, Clarke, EK, Haswell, CC, Averill, CL, Baugh, LA, Bomyea, J, Bruce, SE, Cha, J, Choi, K, Davenport, ND, Densmore, M, du Plessis, S, Forster, GL, Frijling, JL, Gonenc, A, Gruber, S, Grupe, DW, Guenette, JP, Hayes, J, Hofmann, D, Ipser, J, Jovanovic, T, Kelly, S, Kennis, M, Kinzel, P, Koch, SBJ, Koerte, I, Koopowitz, S, Korgaonkar, M, Krystal, J, Lebois, LAM, Li, G, Magnotta, VA, Manthey, A, May, GJ, Menefee, DS, Nawijn, L, Nelson, SM, Neufeld, RWJ, Nitschke, JB, O’Doherty, D, Peverill, M, Ressler, KJ, Roos, A, Sheridan, MA, Sierk, A, Simmons, A, Simons, RM, Simons, JS, Stevens, J, Suarez-Jimenez, B, Sullivan, DR, Théberge, J, Tran, JK, van den Heuvel, L, van der Werff, SJA, van Rooij, SJH, van Zuiden, M, Velez, C, Verfaellie, M, Vermeiren, RRJM, Wade, BSC, Wager, T, Walter, H, Winternitz, S, Wolff, J, York, G, Zhu, Y, Zhu, X, Abdallah, CG, Bryant, R, Daniels, JK, Davidson, RJ, Fercho, KA, Franz, C, Geuze, E, Gordon, EM, Kaufman, ML, Kremen, WS, Lagopoulos, J, Lanius, RA, Lyons, MJ, McCauley, SR, McGlinchey, R, McLaughlin, KA, Milberg, W, Neria, Y, Olff, M, Seedat, S, Shenton, M, Sponheim, SR, Stein, DJ, Stein, MB, Straube, T, Tate, DF, van der Wee, NJA, Veltman, DJ, Wang, L, Wilde, EA, Thompson, PM, Kochunov, P, Jahanshad, N & Morey, RA 2021, 'Altered white matter microstructural organization in posttraumatic stress disorder across 3047 adults: results from the PGC-ENIGMA PTSD consortium', Molecular Psychiatry, vol. 26, no. 8, pp. 4315-4330. https://doi.org/10.1038/s41380-019-0631-x

@article{5a3f4fe1a6cf413f9025689ff52aa8f7,

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

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{\textquoteright}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.",

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

note = "Funding Information: Acknowledgements K99NS096116 to ELD; CIHR, CIMVHR; Dana Foundation (to JBN); the University of Wisconsin Institute for Clinical and Translational Research (to Dr Emma Seppala); a National Science Foundation Graduate Research Fellowship (to DWG); R01MH043454 and T32MH018931 (to RJD); and a core grant to the Waisman Center from the National Institute of Child Health and Human Development (P30HD003352); Defense and Veterans Brain Injury Centers, the U.S. Army Medical Research and Materiel Command (USAMRMC; W81XWH-13-2-0025) and the Chronic Effects of Neurotrauma Consortium (CENC; PT108802-SC104835); Department of Defense award number W81XWH-12-2-0012; ENIGMA was also supported in part by NIH U54EB020403 from the Big Data to Knowledge (BD2K) program, R56AG058854, R01MH116147, R01MH111671, and P41EB015922; Department of Veterans Affairs via support for the National Center for PTSD, NIAAA via its support for (P50) Center for the Translational Neuroscience if Alcohol, and NCATS via its support of (CTSA) Yale Center for Clinical Investigation; DoD W81XWH-10-1-0925; Center for Brain and Behavior Research Pilot Grant; South Dakota Governor{\textquoteright}s Research Center Grant; F32MH109274; Funding from the Bill & Melinda Gates Foundation; Funding from the SAMRC Unit on Risk & Resilience in Mental Disorders; German Research Foundation grant to JKD (numbers DA 1222/4-1 and WA 1539/8-2).; German Research Society (Deutsche Forschungsgemeinschaft, DFG; SFB/TRR 58: C06, C07); I01-CX000715 & I01-CX001542; K01MH118428; K23MH090366; K2CX001772, Clinical Science Research and Development Service, VA Office of Research and Development; MH098212; MH071537; M01RR00039; UL1TR000454; HD071982; HD085850; MH101380; NARSAD 27040; NARSAD Young Investigator, K01MH109836, Young Investigator Grant, Korean Scientists and Engineers Association; NHMRC Program Grant # 1073041; R01AG050595, R01AG022381; R01AG058822; R01EB015611; R01MH105355; R01MH105355, R01DA035484; R01MH111671, R01MH117601, R01AG059874, MJFF 14848; R01MH111671; VISN6 MIRECC; R21MH112956, Anonymous Women's Health Fund, Kasparian Fund, Trauma Scholars Fund, Barlow Family Fund; South African Medical Research Council for the “Shared Roots” Flagship Project, Grant no. MRC-RFA-IFSP-01-2013/SHARED ROOTS” through funding received from the South African National Treasury under its Economic Competitiveness and Support Package. The work by LLvdH reported herein was made possible through funding by the South African Medical Research Council through its Division of Research Capacity Development under the SAMRC CLINICIAN RESEARCHER (M.D PHD) SCHOLARSHIP PROGRAMME from funding received from the South African National Treasury.; South African Research Chairs Initiative in Posttraumatic Stress Disorder through the Department of Science and Technology and the National Research Foundation.; the National Natural Science Foundation of China (No. 31271099, 31471004), the Key Research Program of the Chinese Academy of Sciences (No. ZDRW-XH-2019-4); The study was supported by ZonMw, the Netherlands organization for Health Research and Development (40-00812-98-10041), and by a grant from the Academic Medical Center Research Council (110614) both awarded to MO.; Translational Research Center for TBI and Stress Disorders (TRACTS), a VA Rehabilitation Research and Development (RR&D) Traumatic Brain Injury Center of Excellence (B9254-C) at VA Boston Healthcare System.; VA CSR&D 1IK2CX001680; VISN17 Center of Excellence Pilot funding; VA CSR&D 822-MR-18176 and Senior Career Scientist Award; VA National Center for PTSD; VA RR&D 1IK2RX000709; VA RR&D 1K1RX002325; 1K2RX002922; VA RR&D I01RX000622; CDMRP W81XWH-08–2–0038; W81XWH08-2-0159 (PI: MBS) from the US Department of Defense. The views reflected here are strictly those of the authors and do not constitute endorsement by any of the funding sources listed here. Funding Information: Conflict of interest CGA has served as a consultant, speaker and/or on advisory boards for FSV7, Lundbeck, Genentech and Janssen, and editor of Chronic Stress for Sage Publications, Inc.; he has filed a patent for using mTOR inhibitors to augment the effects of antidepressants (filed on August 20, 2018). RJD is the founder and president of, and serves on the board of directors for, the nonprofit organization Healthy Minds Innovations, Inc. JK is a consultant for AbbVie, Inc., Amgen, Astellas Pharma Global Development, Inc., AstraZeneca Pharmaceuticals, Bio-medisyn Corporation, Bristol-Myers Squibb, Eli Lilly and Company, Euthymics Bioscience, Inc., Neurovance, Inc., FORUM Pharmaceuticals, Janssen Research & Development, Lundbeck Research USA, Novartis Pharma AG, Otsuka America Pharmaceutical, Inc., Sage Therapeutics, Inc., Sunovion Pharmaceuticals, Inc., and Takeda Industries; is on the Scientific Advisory Board for Lohocla Research Corporation, Mnemosyne Pharmaceuticals, Inc., Naurex, Inc., and Pfizer; is a stockholder in Biohaven Pharmaceuticals; holds stock options in Mnemosyne Pharmaceuticals, Inc.; holds patents for Dopamine and Noradrenergic Reuptake Inhibitors in Treatment of Schizophrenia, US Patent No. 5,447,948 (issued September 5, 1995), and Glutamate Modulating Agents in the Treatment of Mental Disorders, U.S. Patent No. 8,778,979 (issued July 15, 2014); and filed a patent for Intranasal Administration of Ketamine to Treat Depression. U.S. Application No. 14/197,767 (filed on March 5, 2014); US application or Patent Cooperation Treaty international application No. 14/306,382 (filed on June 17, 2014). Filed a patent for using mTOR inhibitors to augment the effects of antidepressants (filed on August 20, 2018). NJ received partial research support from Biogen, Inc. (Boston, USA) for research unrelated to the content of this paper. PMT received partial research support from Biogen, Inc. (Boston, USA) for research unrelated to the topic of this paper. Publisher Copyright: {\textcopyright} 2019, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2021",

month = aug,

doi = "10.1038/s41380-019-0631-x",

language = "English (US)",

volume = "26",

pages = "4315--4330",

journal = "Molecular Psychiatry",

issn = "1359-4184",

publisher = "Nature Publishing Group",

number = "8",

}

TY - JOUR

T1 - Altered white matter microstructural organization in posttraumatic stress disorder across 3047 adults

T2 - results from the PGC-ENIGMA PTSD consortium

AU - Dennis, Emily L.

AU - Disner, Seth G.

AU - Fani, Negar

AU - Salminen, Lauren E.

AU - Logue, Mark

AU - Clarke, Emily K.

AU - Haswell, Courtney C.

AU - Averill, Christopher L.

AU - Baugh, Lee A.

AU - Bomyea, Jessica

AU - Bruce, Steven E.

AU - Cha, Jiook

AU - Choi, Kyle

AU - Davenport, Nicholas D.

AU - Densmore, Maria

AU - du Plessis, Stefan

AU - Forster, Gina L.

AU - Frijling, Jessie L.

AU - Gonenc, Atilla

AU - Gruber, Staci

AU - Grupe, Daniel W.

AU - Guenette, Jeffrey P.

AU - Hayes, Jasmeet

AU - Hofmann, David

AU - Ipser, Jonathan

AU - Jovanovic, Tanja

AU - Kelly, Sinead

AU - Kennis, Mitzy

AU - Kinzel, Philipp

AU - Koch, Saskia B.J.

AU - Koerte, Inga

AU - Koopowitz, Sheri

AU - Korgaonkar, Mayuresh

AU - Krystal, John

AU - Lebois, Lauren A.M.

AU - Li, Gen

AU - Magnotta, Vincent A.

AU - Manthey, Antje

AU - May, Geoff J.

AU - Menefee, Deleene S.

AU - Nawijn, Laura

AU - Nelson, Steven M.

AU - Neufeld, Richard W.J.

AU - Nitschke, Jack B.

AU - O’Doherty, Daniel

AU - Peverill, Matthew

AU - Ressler, Kerry J.

AU - Roos, Annerine

AU - Sheridan, Margaret A.

AU - Sierk, Anika

AU - Simmons, Alan

AU - Simons, Raluca M.

AU - Simons, Jeffrey S.

AU - Stevens, Jennifer

AU - Suarez-Jimenez, Benjamin

AU - Sullivan, Danielle R.

AU - Théberge, Jean

AU - Tran, Jana K.

AU - van den Heuvel, Leigh

AU - van der Werff, Steven J.A.

AU - van Rooij, Sanne J.H.

AU - van Zuiden, Mirjam

AU - Velez, Carmen

AU - Verfaellie, Mieke

AU - Vermeiren, Robert R.J.M.

AU - Wade, Benjamin S.C.

AU - Wager, Tor

AU - Walter, Henrik

AU - Winternitz, Sherry

AU - Wolff, Jonathan

AU - York, Gerald

AU - Zhu, Ye

AU - Zhu, Xi

AU - Abdallah, Chadi G.

AU - Bryant, Richard

AU - Daniels, Judith K.

AU - Davidson, Richard J.

AU - Fercho, Kelene A.

AU - Franz, Carol

AU - Geuze, Elbert

AU - Gordon, Evan M.

AU - Kaufman, Milissa L.

AU - Kremen, William S.

AU - Lagopoulos, Jim

AU - Lanius, Ruth A.

AU - Lyons, Michael J.

AU - McCauley, Stephen R.

AU - McGlinchey, Regina

AU - McLaughlin, Katie A.

AU - Milberg, William

AU - Neria, Yuval

AU - Olff, Miranda

AU - Seedat, Soraya

AU - Shenton, Martha

AU - Sponheim, Scott R.

AU - Stein, Dan J.

AU - Stein, Murray B.

AU - Straube, Thomas

AU - Tate, David F.

AU - van der Wee, Nic J.A.

AU - Veltman, Dick J.

AU - Wang, Li

AU - Wilde, Elisabeth A.

AU - Thompson, Paul M.

AU - Kochunov, Peter

AU - Jahanshad, Neda

AU - Morey, Rajendra A.

N1 - Funding Information: Acknowledgements K99NS096116 to ELD; CIHR, CIMVHR; Dana Foundation (to JBN); the University of Wisconsin Institute for Clinical and Translational Research (to Dr Emma Seppala); a National Science Foundation Graduate Research Fellowship (to DWG); R01MH043454 and T32MH018931 (to RJD); and a core grant to the Waisman Center from the National Institute of Child Health and Human Development (P30HD003352); Defense and Veterans Brain Injury Centers, the U.S. Army Medical Research and Materiel Command (USAMRMC; W81XWH-13-2-0025) and the Chronic Effects of Neurotrauma Consortium (CENC; PT108802-SC104835); Department of Defense award number W81XWH-12-2-0012; ENIGMA was also supported in part by NIH U54EB020403 from the Big Data to Knowledge (BD2K) program, R56AG058854, R01MH116147, R01MH111671, and P41EB015922; Department of Veterans Affairs via support for the National Center for PTSD, NIAAA via its support for (P50) Center for the Translational Neuroscience if Alcohol, and NCATS via its support of (CTSA) Yale Center for Clinical Investigation; DoD W81XWH-10-1-0925; Center for Brain and Behavior Research Pilot Grant; South Dakota Governor’s Research Center Grant; F32MH109274; Funding from the Bill & Melinda Gates Foundation; Funding from the SAMRC Unit on Risk & Resilience in Mental Disorders; German Research Foundation grant to JKD (numbers DA 1222/4-1 and WA 1539/8-2).; German Research Society (Deutsche Forschungsgemeinschaft, DFG; SFB/TRR 58: C06, C07); I01-CX000715 & I01-CX001542; K01MH118428; K23MH090366; K2CX001772, Clinical Science Research and Development Service, VA Office of Research and Development; MH098212; MH071537; M01RR00039; UL1TR000454; HD071982; HD085850; MH101380; NARSAD 27040; NARSAD Young Investigator, K01MH109836, Young Investigator Grant, Korean Scientists and Engineers Association; NHMRC Program Grant # 1073041; R01AG050595, R01AG022381; R01AG058822; R01EB015611; R01MH105355; R01MH105355, R01DA035484; R01MH111671, R01MH117601, R01AG059874, MJFF 14848; R01MH111671; VISN6 MIRECC; R21MH112956, Anonymous Women's Health Fund, Kasparian Fund, Trauma Scholars Fund, Barlow Family Fund; South African Medical Research Council for the “Shared Roots” Flagship Project, Grant no. MRC-RFA-IFSP-01-2013/SHARED ROOTS” through funding received from the South African National Treasury under its Economic Competitiveness and Support Package. The work by LLvdH reported herein was made possible through funding by the South African Medical Research Council through its Division of Research Capacity Development under the SAMRC CLINICIAN RESEARCHER (M.D PHD) SCHOLARSHIP PROGRAMME from funding received from the South African National Treasury.; South African Research Chairs Initiative in Posttraumatic Stress Disorder through the Department of Science and Technology and the National Research Foundation.; the National Natural Science Foundation of China (No. 31271099, 31471004), the Key Research Program of the Chinese Academy of Sciences (No. ZDRW-XH-2019-4); The study was supported by ZonMw, the Netherlands organization for Health Research and Development (40-00812-98-10041), and by a grant from the Academic Medical Center Research Council (110614) both awarded to MO.; Translational Research Center for TBI and Stress Disorders (TRACTS), a VA Rehabilitation Research and Development (RR&D) Traumatic Brain Injury Center of Excellence (B9254-C) at VA Boston Healthcare System.; VA CSR&D 1IK2CX001680; VISN17 Center of Excellence Pilot funding; VA CSR&D 822-MR-18176 and Senior Career Scientist Award; VA National Center for PTSD; VA RR&D 1IK2RX000709; VA RR&D 1K1RX002325; 1K2RX002922; VA RR&D I01RX000622; CDMRP W81XWH-08–2–0038; W81XWH08-2-0159 (PI: MBS) from the US Department of Defense. The views reflected here are strictly those of the authors and do not constitute endorsement by any of the funding sources listed here. Funding Information: Conflict of interest CGA has served as a consultant, speaker and/or on advisory boards for FSV7, Lundbeck, Genentech and Janssen, and editor of Chronic Stress for Sage Publications, Inc.; he has filed a patent for using mTOR inhibitors to augment the effects of antidepressants (filed on August 20, 2018). RJD is the founder and president of, and serves on the board of directors for, the nonprofit organization Healthy Minds Innovations, Inc. JK is a consultant for AbbVie, Inc., Amgen, Astellas Pharma Global Development, Inc., AstraZeneca Pharmaceuticals, Bio-medisyn Corporation, Bristol-Myers Squibb, Eli Lilly and Company, Euthymics Bioscience, Inc., Neurovance, Inc., FORUM Pharmaceuticals, Janssen Research & Development, Lundbeck Research USA, Novartis Pharma AG, Otsuka America Pharmaceutical, Inc., Sage Therapeutics, Inc., Sunovion Pharmaceuticals, Inc., and Takeda Industries; is on the Scientific Advisory Board for Lohocla Research Corporation, Mnemosyne Pharmaceuticals, Inc., Naurex, Inc., and Pfizer; is a stockholder in Biohaven Pharmaceuticals; holds stock options in Mnemosyne Pharmaceuticals, Inc.; holds patents for Dopamine and Noradrenergic Reuptake Inhibitors in Treatment of Schizophrenia, US Patent No. 5,447,948 (issued September 5, 1995), and Glutamate Modulating Agents in the Treatment of Mental Disorders, U.S. Patent No. 8,778,979 (issued July 15, 2014); and filed a patent for Intranasal Administration of Ketamine to Treat Depression. U.S. Application No. 14/197,767 (filed on March 5, 2014); US application or Patent Cooperation Treaty international application No. 14/306,382 (filed on June 17, 2014). Filed a patent for using mTOR inhibitors to augment the effects of antidepressants (filed on August 20, 2018). NJ received partial research support from Biogen, Inc. (Boston, USA) for research unrelated to the content of this paper. PMT received partial research support from Biogen, Inc. (Boston, USA) for research unrelated to the topic of this paper. Publisher Copyright: © 2019, The Author(s), under exclusive licence to Springer Nature Limited.

PY - 2021/8

Y1 - 2021/8

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85077020994&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85077020994&partnerID=8YFLogxK

U2 - 10.1038/s41380-019-0631-x

DO - 10.1038/s41380-019-0631-x

M3 - Article

C2 - 31857689

AN - SCOPUS:85077020994

VL - 26

SP - 4315

EP - 4330

JO - Molecular Psychiatry

JF - Molecular Psychiatry

SN - 1359-4184

IS - 8

ER -

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

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