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

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Altered white matter microstructural organization in posttraumatic stress disorder across 3047 adults: results from the PGC-ENIGMA PTSD consortium.
Molecular Psychiatry ( IF 9.6 ) Pub Date : 2019-12-19 , DOI: 10.1038/s41380-019-0631-x
Emily L Dennis _{1,

2,

3,

4} , Seth G Disner _{5,

6} , Negar Fani ₇ , Lauren E Salminen ₂ , Mark Logue _{8,

9,

10,

11} , Emily K Clarke _{12,

13} , Courtney C Haswell _{12,

13} , Christopher L Averill ₁₄ , Lee A Baugh _{15,

16,

17} , Jessica Bomyea _{18,

19} , Steven E Bruce ₂₀ , Jiook Cha _{21,

22} , Kyle Choi ₂₃ , Nicholas D Davenport _{5,

6} , Maria Densmore _{24,

25} , Stefan du Plessis ₂₆ , Gina L Forster _{15,

16,

27} , Jessie L Frijling ₂₈ , Atilla Gonenc _{29,

30} , Staci Gruber _{29,

30} , Daniel W Grupe ₃₁ , Jeffrey P Guenette ₃₂ , Jasmeet Hayes ₃₃ , David Hofmann ₃₄ , Jonathan Ipser ₃₅ , Tanja Jovanovic _{7,

36} , Sinead Kelly _{1,

37} , Mitzy Kennis _{38,

39} , Philipp Kinzel _{1,

40} , Saskia B J Koch _{28,

41} , Inga Koerte _{1,

40} , Sheri Koopowitz ₃₅ , Mayuresh Korgaonkar ₄₂ , John Krystal ₁₄ , Lauren A M Lebois _{30,

43} , Gen Li _{44,

45} , Vincent A Magnotta ₄₆ , Antje Manthey ₄₇ , Geoff J May _{48,

49,

50,

51} , Deleene S Menefee _{52,

53} , Laura Nawijn _{28,

54} , Steven M Nelson _{48,

49,

51} , Richard W J Neufeld _{24,

55,

56,

57} , Jack B Nitschke ₅₈ , Daniel O'Doherty ₅₉ , Matthew Peverill ₆₀ , Kerry J Ressler _{7,

30,

41} , Annerine Roos ₆₁ , Margaret A Sheridan ₆₂ , Anika Sierk ₄₇ , Alan Simmons _{18,

19} , Raluca M Simons _{16,

63} , Jeffrey S Simons _{17,

63} , Jennifer Stevens ₇ , Benjamin Suarez-Jimenez _{21,

22} , Danielle R Sullivan _{8,

9} , Jean Théberge _{24,

25,

64} , Jana K Tran ₆₅ , Leigh van den Heuvel ₂₆ , Steven J A van der Werff _{66,

67} , Sanne J H van Rooij ₇ , Mirjam van Zuiden ₂₈ , Carmen Velez _{3,

68} , Mieke Verfaellie _{9,

69} , Robert R J M Vermeiren ₆₆ , Benjamin S C Wade _{3,

68,

70} , Tor Wager ₇₁ , Henrik Walter ₄₇ , Sherry Winternitz _{30,

72} , Jonathan Wolff ₄₃ , Gerald York _{73,

74} , Ye Zhu _{44,

45} , Xi Zhu _{21,

22} , Chadi G Abdallah ₁₄ , Richard Bryant ₇₅ , Judith K Daniels ₇₆ , Richard J Davidson _{31,

58,

77} , Kelene A Fercho _{15,

16,

17,

78} , Carol Franz _{19,

79} , Elbert Geuze _{38,

39} , Evan M Gordon _{48,

49,

51} , Milissa L Kaufman _{30,

72} , William S Kremen _{18,

19,

79} , Jim Lagopoulos ₅₉ , Ruth A Lanius _{24,

25,

56} , Michael J Lyons ₈₀ , Stephen R McCauley _{81,

82} , Regina McGlinchey _{30,

83} , Katie A McLaughlin ₈₄ , William Milberg _{30,

85} , Yuval Neria _{21,

22} , Miranda Olff _{28,

85} , Soraya Seedat ₆₁ , Martha Shenton _{1,

86} , Scott R Sponheim _{5,

6} , Dan J Stein ₃₅ , Murray B Stein _{19,

87} , Thomas Straube ₃₄ , David F Tate _{3,

68} , Nic J A van der Wee _{66,

67} , Dick J Veltman ₅₄ , Li Wang _{44,

45} , Elisabeth A Wilde _{3,

82,

88} , Paul M Thompson ₂ , Peter Kochunov ₈₉ , Neda Jahanshad ₂ , Rajendra A Morey _{12,

13}

Affiliation

Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Boston, MA, USA.
Imaging Genetics Center, Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of USC, Marina del Rey, CA, USA.
Department of Neurology, University of Utah, Salt Lake City, UT, USA.
Stanford Neurodevelopment, Affect, and Psychopathology Laboratory, Stanford, CA, USA.
Minneapolis VA Health Care System, Minneapolis, MN, USA.
Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA.
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
National Center for PTSD, VA Boston Healthcare System, Boston, MA, USA.
Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA.
Biomedical Genetics, Boston University School of Medicine, Boston, MA, USA.
Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Brain Imaging and Analysis Center, Duke University, Durham, NC, USA.
VISN 6 MIRECC, Durham VA, Durham, NC, USA.
Clinical Neuroscience Division, National Center for PTSD; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, USA.
Center for Brain and Behavior Research, University of South Dakota, Vermillion, SD, USA.
Sioux Falls VA Health Care System, Sioux Falls, SD, USA.
Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, La Jolla, CA, USA.
Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
Department of Psychological Sciences, Center for Trauma Recovery University of Missouri-St. Louis, St. Louis, MO, USA.
Department of Psychiatry, Columbia University Medical Center, New York, NY, USA.
New York State Psychiatric Institute, New York, NY, USA.
Health Services Research Center, University of California, San Diego, CA, USA.
Department of Psychiatry, Western University, London, ON, Canada.
Imaging Division, Lawson Health Research Institute, London, ON, Canada.
Department of Psychiatry, Stellenbosch University, Stellenbosch, South Africa.
Brain Health Research Centre, Department of Anatomy, University of Otago, Dunedin, 9054, New Zealand.
Department of Psychiatry, Amsterdam Neuroscience, Amsterdam University Medical Centers, Location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Cognitive and Clinical Neuroimaging Core, McLean Hospital, Belmont, MA, USA.
Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
Center for Healthy Minds, University of Wisconsin-Madison, Madison, WI, USA.
Division of Neuroradiology, Brigham and Women's Hospital, Boston, MA, USA.
Department of Psychology, The Ohio State University, Columbus, OH, USA.
Institute of Medical Psychology and Systems Neuroscience, University of Münster, Münster, Germany.
SA Medical Research Council Unit on Risk & Resilience in Mental Disorders, Dept of Psychiatry & Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
Department of Psychiatry and Behavioral Neuroscience, Wayne State University School of Medicine, Detroit, MI, USA.
Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Brain Center Rudolf Magnus, Department of Psychiatry, UMCU, Utrecht, The Netherlands.
Brain Research and Innovation Centre, Ministry of Defence, Utrecht, The Netherlands.
Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital, Ludwig-Maximilians-Universität, Munich, Germany.
Donders Institute for Brain, Cognition and Behavior, Centre for Cognitive Neuroimaging, Radboud University Nijmegen, Nijmegen, The Netherlands.
Brain Dynamics Centre, Westmead Institute of Medical Research, University of Sydney, Westmead, NSW, Australia.
Division of Depression and Anxiety Disorders, McLean Hospital, Belmont, MA, USA.
Laboratory for Traumatic Stress Studies, CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.
Department of Psychology, University of Chinese Academy of Sciences, Beijing, China.
Departments of Radiology, Psychiatry, and Biomedical Engineering, University of Iowa, Iowa City, IA, USA.
University Medical Centre Charite, Berlin, Germany.
VISN 17 Center of Excellence for Research on Returning War Veterans, Waco, TX, USA.
Department of Psychology and Neuroscience, Baylor University, Waco, TX, USA.
Department of Psychiatry and Behavioral Science, Texas A&M Health Science Center, Bryan, TX, USA.
Center for Vital Longevity, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, TX, USA.
Menninger Department of Psychiatry, Baylor College of Medicine, Houston, TX, USA.
South Central MIRECC, Houston, TX, USA.
Department of Psychiatry, Amsterdam University Medical Centers, Location VU University Medical Center, VU University, Amsterdam, The Netherlands.
Department of Psychology, Western University, London, ON, Canada.
Department of Neuroscience, Western University, London, ON, Canada.
Department of Psychology, University of British Columbia, Okanagan, BC, Canada.
Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, USA.
University of the Sunshine Coast, Birtinya, QLD, Australia.
Department of Psychology, University of Washington, Seattle, WA, USA.
South African Medical Research Council / Stellenbosch University Genomics of Brain Disorders Research Unit, Department of Psychiatry, Stellenbosch University, Cape Town, South Africa.
Department of Psychology and Brain Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Department of Psychology, University of South Dakota, Vermillion, SD, USA.
Department of Medical Biophysics, Western University, London, ON, Canada.
Houston Fire Department, Houston, TX, USA.
Department of Psychiatry, LUMC, Leiden, The Netherlands.
Leiden Institute for Brain and Cognition, Leiden, The Netherlands.
Missouri Institute of Mental Health and University of Missouri, St Louis, MO, USA.
Memory Disorders Research Center, VA Boston Healthcare System, Boston, MA, USA.
Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, University of California, Los Angeles, Los Angeles, CA, USA.
Dartmouth College, Hanover, NH, USA.
Division of Women's Mental Health, McLean Hospital, Belmont, MA, USA.
Joint Trauma System, 3698 Chambers Pass, Joint Base San Antonio, Fort Sam Houston, TX, USA.
Alaska Radiology Associates, Anchorage, AK, USA.
School of Psychology, University of New South Wales, Sydney, NSW, Australia.
Department of Clinical Psychology, University of Groningen, Groningen, The Netherlands.
Department of Psychology, University of Wisconsin-Madison, Madison, WI, USA.
Civil Aerospace Medical Institute, US Federal Aviation Administration, Oklahoma City, OK, USA.
Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA, USA.
Dept. of Psychological & Brain Sciences, Boston University, Boston, MA, USA.
Departments of Neurology and Pediatrics, Baylor College of Medicine, Houston, TX, USA.
H. Ben Taub Department of Physical Medicine and Rehabilitation, Baylor College of Medicine, Houston, TX, USA.
Geriatric Research Educational and Clinical Center and Translational Research Center for TBI and Stress Disorders, VA Boston Healthcare System, Boston, MA, USA.
Department of Psychology, Harvard University, Cambridge, MA, USA.
ARQ National Psychotrauma Centre, Diemen, The Netherlands.
VA Boston Healthcare System, Brockton Division, Brockton, MA, USA.
Department of Family Medicine and Public Health, University of California, San Diego, La Jolla, CA, USA.
George E. Whalen Veterans Affairs Medical Center, Salt Lake City, UT, USA.
Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, USA.

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.

中文翻译：

3047 名成年人创伤后应激障碍中白质微结构组织的改变：来自 PGC-ENIGMA PTSD 联盟的结果。

越来越多的研究使用扩散 MRI (dMRI) 检查创伤后应激障碍 (PTSD) 患者白质组织的变化，但结果好坏参半，部分原因可能是研究中的样本量相对较小。结构连接的改变可能既是 PTSD 的神经生物学脆弱性，也是 PTSD 的结果。为了找到可靠的效果，我们对目前参加 PGC-ENIGMA PTSD 工作组（精神病基因组学联盟和通过 Meta 增强神经影像遗传学的联合伙伴关系）的 28 个队列中的 3047 名个体的 dMRI 指标进行了多队列分析。 -分析联盟）。通过比较 1426 名 PTSD 患者和 1621 名年龄在 18-83 岁之间的对照者（2174 名男性/873 名女性）的全脑区域白质指标（其中 92% 遭受过创伤），我们报告了 PTSD 与测量到的白质组织破坏之间的关联胼胝体绒毡层区域的各向异性分数 (FA) 较低（Cohen d = -0.11，p = 0.0055）。绒毡层连接左右海马体，其结构和功能一直与创伤后应激障碍有关。即使考虑了多个潜在混杂变量的影响，结果仍然一致：童年创伤暴露、共病抑郁症、创伤性脑损伤史、当前酗酒或依赖以及当前使用精神药物。我们的结果表明，创伤后应激障碍可能与更广泛的海马网络的改变有关。

更新日期：2019-12-19

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