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

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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

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Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature Limited.

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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

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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.",

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note = "Publisher Copyright: {\textcopyright} 2019, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2021",

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

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

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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.

PY - 2021/8

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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.

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

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