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Hippocampal subfield volumes are uniquely affected in PTSD and depression: International analysis of 31 cohorts from the PGC-ENIGMA PTSD Working Group

View ORCID ProfileLauren E. Salminen, Philipp G. Sämann, Yuanchao Zheng, Emily L. Dennis, Emily K. Clarke-Rubright, Neda Jahanshad, Juan E. Iglesias, Christopher D. Whelan, Steven E. Bruce, Jasmeet P. Hayes, Soraya Seedat, Christopher L. Averill, Lee A. Baugh, Jessica Bomyea, Joanna Bright, Chanellé J. Buckle, Kyle Choi, Nicholas D. Davenport, Richard J. Davidson, Maria Densmore, Seth G. Disner, Stefan du Plessis, Jeremy A. Elman, Negar Fani, Gina L. Forster, Carol E. Franz, Jessie L. Frijling, Atilla Gonenc, Staci A. Gruber, Daniel W. Grupe, Jeffrey P. Guenette, Courtney C. Haswell, David Hofmann, Michael Hollifield, Babok Hosseini, Anna R. Hudson, Jonathan Ipser, Tanja Jovanovic, Amy Kennedy-Krage, Mitzy Kennis, Anthony King, Philipp Kinzel, Saskia B. J. Koch, Inga Koerte, Sheri M. Koopowitz, Mayuresh S. Korgaonkar, William S. Kremen, John Krystal, Lauren A. M. Lebois, Ifat Levy, Michael J. Lyons, Vincent A. Magnotta, Antje Manthey, Soichiro Nakahara, Laura Nawijn, Richard W. J. Neufeld, Jack B. Nitschke, Daniel C. M. O’Doherty, Robert H. Paul, Matthew Peverill, Faisal M. Rashid, Kerry J. Ressler, Annerine Roos, Christian Schmahl, Margaret A. Sheridan, Anika Sierk, Alan N. Simmons, Jeffrey S. Simons, Raluca M. Simons, Murray B. Stein, Jennifer S. Stevens, Benjamin Suarez-Jimenez, Jean Théberge, Kathleen Thomaes, Sophia I. Thomopoulos, Leigh L. van den Heuvel, Steven J. A. van der Werff, Theo G. M. van Erp, Sanne J. H. van Rooij, Mirjam van Zuiden, Tim Varkevisser, Robert R. J. M. Vermeiren, Tor D. Wager, Henrik Walter, Xin Wang, Sherry Winternitz, Jonathan D. Wolff, Kristen Wrocklage, Xi Zhu, Christopher R. K. Ching, Tiril P. Gurholt, Unn K. Haukvik, Ingrid Agartz, Chadi G. Abdallah, Richard Bryant, Judith K. Daniels, Michael DeBellis, Kelene A. Fercho, Elbert Geuze, Ilan Harpaz-Rotem, Julia I. Herzog, Milissa L. Kaufman, Jim Lagopoulos, Ruth A. Lanius, Katie A. McLaughlin, Sven C. Mueller, Yuval Neria, Miranda Olff, K. Luan Phan, Martha E. Shenton, Scott R. Sponheim, Dan J. Stein, Thomas Straube, Nic J. A. van der Wee, Dick J. Veltman, Paul M. Thompson, Rajendra A. Morey, Mark W. Logue, for the ENIGMA-PGC-PTSD Working Group
doi: https://doi.org/10.1101/739094
Lauren E. Salminen
1Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of USC, Marina del Rey, CA, USA
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  • ORCID record for Lauren E. Salminen
  • For correspondence: lauren.salminen@loni.usc.edu
Philipp G. Sämann
2Max Planck Institute of Psychiatry, Munich, Germany
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Yuanchao Zheng
3Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
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Emily L. Dennis
1Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of USC, Marina del Rey, CA, USA
4Psychiatry Neuroimaging Laboratory, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA, USA
5Stanford Neurodevelopment, Affect, and Psychopathology Laboratory, Stanford, CA, USA
6Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA
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Emily K. Clarke-Rubright
7Brain Imaging and Analysis Center, Duke University, Durham, NC, USA
8VISN 6 MIRECC, Durham VA, Durham, NC, USA
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Neda Jahanshad
1Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of USC, Marina del Rey, CA, USA
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Juan E. Iglesias
9Centre for Medical Image Computing (CMIC), Department of Medical Physics and Biomedical Engineering, University College London, London, UK
10Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
11Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA
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Christopher D. Whelan
12Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland
13Research and Early Development, Biogen Inc., Cambridge, MA, USA
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Steven E. Bruce
14Department of Psychological Sciences, Center for Trauma Recovery, University of Missouri St. Louis, St. Louis, MO, USA
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Jasmeet P. Hayes
15Department of Psychology, The Ohio State University, Columbus, OH, USA
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Soraya Seedat
16Department of Psychiatry, Stellenbosch University, Cape Town, South Africa
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Christopher L. Averill
17Clinical Neuroscience Division, National Center for PTSD, West Haven, CT, USA
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Lee A. Baugh
18Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, USA
19Center for Brain and Behavior Research, University of South Dakota, Vermillion, SD, USA
20Sioux Falls VA Health Care System, Sioux Falls, SD, USA
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Jessica Bomyea
21VA San Diego Healthcare System, Center of Excellence for Stress and Mental Health, San Diego, CA, USA
22Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA
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Joanna Bright
1Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of USC, Marina del Rey, CA, USA
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Chanellé J. Buckle
16Department of Psychiatry, Stellenbosch University, Cape Town, South Africa
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Kyle Choi
23University of California, San Diego, La Jolla, CA, USA
24Health Services Research Center
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Nicholas D. Davenport
25Minneapolis VA Health Care System, Minneapolis, MN, USA
26Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA
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Richard J. Davidson
27Center for Healthy Minds, University of Wisconsin-Madison, WI, USA
28Department of Psychology, University of Wisconsin-Madison, Madison, WI, USA
29Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, USA
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Maria Densmore
30Department of Psychiatry, University of Western Ontario, London, ON, Canada
31Imaging Division, Lawson Health Research Institute, London, ON, Canada
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Seth G. Disner
25Minneapolis VA Health Care System, Minneapolis, MN, USA
26Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA
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Stefan du Plessis
16Department of Psychiatry, Stellenbosch University, Cape Town, South Africa
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Jeremy A. Elman
22Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA
32Center for Behavior Genetics of Aging, San Diego, CA, USA
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Negar Fani
33Department of Psychiatry and Behavioral Science, Emory University, Atlanta, GA, USA
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Gina L. Forster
18Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, USA
19Center for Brain and Behavior Research, University of South Dakota, Vermillion, SD, USA
34Brain Health Research Centre, Department of Anatomy, University of Otago, Dunedin, New Zealand
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Carol E. Franz
22Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA
32Center for Behavior Genetics of Aging, San Diego, CA, USA
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Jessie L. Frijling
35Department of Psychiatry, Amsterdam University Medical Centers, Location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
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Atilla Gonenc
36Cognitive and Clinical Neuroimaging Core, McLean Hospital, Belmont, MA, USA
37Department of Psychiatry, Harvard Medical School, Boston, MA, USA
38Marijuana Investigations for Neuroscientific Discovery (MIND), McLean Hospital, Belmont, MA, USA
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Staci A. Gruber
36Cognitive and Clinical Neuroimaging Core, McLean Hospital, Belmont, MA, USA
37Department of Psychiatry, Harvard Medical School, Boston, MA, USA
38Marijuana Investigations for Neuroscientific Discovery (MIND), McLean Hospital, Belmont, MA, USA
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Daniel W. Grupe
27Center for Healthy Minds, University of Wisconsin-Madison, WI, USA
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Jeffrey P. Guenette
39Division of Neuroradiology, Brigham and Women’s Hospital, Boston, MA, USA
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Courtney C. Haswell
7Brain Imaging and Analysis Center, Duke University, Durham, NC, USA
8VISN 6 MIRECC, Durham VA, Durham, NC, USA
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David Hofmann
40Institute of Medical Psychology and Systems Neuroscience, University of Münster, Münster, Germany
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Michael Hollifield
41Program for Traumatic Stress, Tibor Rubin VA Medical Center, Long Beach, CA, USA
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Babok Hosseini
42Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA
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Anna R. Hudson
43Department of Experimental Clinical and Health Psychology, Ghent University, Belgium
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Jonathan Ipser
44Department of Psychiatry, University of Cape Town, Cape Town, South Africa
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Tanja Jovanovic
45Department of Psychiatry, Wayne State University, Detroit, MI, USA
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Amy Kennedy-Krage
42Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA
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Mitzy Kennis
46Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands
47Brain Research and Innovation Centre, Ministry of Defence, Utrecht, The Netherlands
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Anthony King
48Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA
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Philipp Kinzel
49Department of Child and Adolescent Psychiatry, Psychosomatic and Psychotherapy, Ludwig-Maximilians-Universität, Munich, Germany
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Saskia B. J. Koch
35Department of Psychiatry, Amsterdam University Medical Centers, Location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
50Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging, Radboud University Nijmegen, Nijmegen, The Netherlands
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Inga Koerte
4Psychiatry Neuroimaging Laboratory, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA, USA
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Sheri M. Koopowitz
44Department of Psychiatry, University of Cape Town, Cape Town, South Africa
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Mayuresh S. Korgaonkar
51Brain Dynamics Centre, Westmead Institute of Medical Research, University of Sydney, Westmead, NSW, Australia
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William S. Kremen
21VA San Diego Healthcare System, Center of Excellence for Stress and Mental Health, San Diego, CA, USA
22Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA
32Center for Behavior Genetics of Aging, San Diego, CA, USA
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John Krystal
17Clinical Neuroscience Division, National Center for PTSD, West Haven, CT, USA
52Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
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Lauren A. M. Lebois
37Department of Psychiatry, Harvard Medical School, Boston, MA, USA
53Division of Depression and Anxiety Disorders, McLean Hospital, Belmont, MA, USA
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Ifat Levy
17Clinical Neuroscience Division, National Center for PTSD, West Haven, CT, USA
54Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA
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Michael J. Lyons
55Department of Psychological & Brain Sciences, Boston University, Boston, MA, USA
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Vincent A. Magnotta
56Departments of Radiology, Psychiatry, and Biomedical Engineering, University of Iowa, Iowa City, IA, USA
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Antje Manthey
57University Medical Centre Charite, Berlin, Germany
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Soichiro Nakahara
58Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA
59Unit 2, Candidate Discovery Science Labs, Drug Discovery Research, Astellas Pharma Inc, 21, Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan
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Laura Nawijn
35Department of Psychiatry, Amsterdam University Medical Centers, Location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
60Department of Psychiatry, Amsterdam University Medical Centers, Location VU University Medical Center, VU University, Amsterdam, The Netherlands
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Richard W. J. Neufeld
30Department of Psychiatry, University of Western Ontario, London, ON, Canada
61Department of Psychology, University of Western Ontario, London, ON, Canada
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Jack B. Nitschke
29Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, USA
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Daniel C. M. O’Doherty
62University of the Sunshine Coast, Birtinya, QLD, Australia
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Robert H. Paul
63Missouri Institute of Mental Health, University of Missouri-St. Louis, St. Louis MO, USA
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Matthew Peverill
64Department of Psychology, University of Washington, Seattle, WA, USA
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Faisal M. Rashid
1Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of USC, Marina del Rey, CA, USA
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Kerry J. Ressler
53Division of Depression and Anxiety Disorders, McLean Hospital, Belmont, MA, USA
65Department of Psychiatry, Boston Children’s Hospital and Harvard Medical School, Boston, MA, USA
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Annerine Roos
66SU/UCT MRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry, Stellenbosch University, Stellenbosch, South Africa
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Christian Schmahl
30Department of Psychiatry, University of Western Ontario, London, ON, Canada
67Department of Psychosomatic Medicine and Psychotherapy, Central Institute of Mental Health Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
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Margaret A. Sheridan
68Department of Psychology and Brain Sciences, University of North Carolina at Chapel Hill, NC, USA
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Anika Sierk
57University Medical Centre Charite, Berlin, Germany
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Alan N. Simmons
21VA San Diego Healthcare System, Center of Excellence for Stress and Mental Health, San Diego, CA, USA
22Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA
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Jeffrey S. Simons
20Sioux Falls VA Health Care System, Sioux Falls, SD, USA
69Department of Psychology, University of South Dakota, Vermillion, SD, USA
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Raluca M. Simons
19Center for Brain and Behavior Research, University of South Dakota, Vermillion, SD, USA
69Department of Psychology, University of South Dakota, Vermillion, SD, USA
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Murray B. Stein
22Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA
70Department of Family Medicine and Public Health, University of California, San Diego, La Jolla, CA, USA
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Jennifer S. Stevens
33Department of Psychiatry and Behavioral Science, Emory University, Atlanta, GA, USA
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Benjamin Suarez-Jimenez
71Department of Psychiatry, Columbia University Medical Center, New York, NY, USA
72New York State Psychiatric Institute, New York, NY, USA
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Jean Théberge
30Department of Psychiatry, University of Western Ontario, London, ON, Canada
31Imaging Division, Lawson Health Research Institute, London, ON, Canada
73Department of Medical Biophysics, University of Western Ontario, London, ON, Canada
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Kathleen Thomaes
74GGZinGeest & VU Medical Center, Amsterdam, Department of Anatomy & Neurosciences, Amsterdam, The Netherlands
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Sophia I. Thomopoulos
1Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of USC, Marina del Rey, CA, USA
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Leigh L. van den Heuvel
16Department of Psychiatry, Stellenbosch University, Cape Town, South Africa
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Steven J. A. van der Werff
75Psychiatry, LUMC, Leiden, The Netherlands
76Leiden Institute for Brain and Cognition, Leiden, The Netherlands
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Theo G. M. van Erp
77Clinical Translational Neuroscience Laboratory, Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA
78Center for the Neurobiology of Learning and Memory, University of California, Irvine, Irvine, CA, USA
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Sanne J. H. van Rooij
33Department of Psychiatry and Behavioral Science, Emory University, Atlanta, GA, USA
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Mirjam van Zuiden
35Department of Psychiatry, Amsterdam University Medical Centers, Location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
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Tim Varkevisser
46Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands
47Brain Research and Innovation Centre, Ministry of Defence, Utrecht, The Netherlands
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Robert R. J. M. Vermeiren
79Child and Adolescent Psychiatry, LUMC, Leiden, The Netherlands
80Youz - Parnassia Group
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Tor D. Wager
81Dartmouth College, Hanover, NH, USA
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Henrik Walter
57University Medical Centre Charite, Berlin, Germany
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Xin Wang
82Department of Psychiatry, University of Toledo, OH, USA
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Sherry Winternitz
37Department of Psychiatry, Harvard Medical School, Boston, MA, USA
83Division of Women’s Mental Health, McLean Hospital, Belmont, MA, USA
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Jonathan D. Wolff
53Division of Depression and Anxiety Disorders, McLean Hospital, Belmont, MA, USA
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Kristen Wrocklage
17Clinical Neuroscience Division, National Center for PTSD, West Haven, CT, USA
52Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
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Xi Zhu
71Department of Psychiatry, Columbia University Medical Center, New York, NY, USA
72New York State Psychiatric Institute, New York, NY, USA
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Christopher R. K. Ching
1Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of USC, Marina del Rey, CA, USA
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Tiril P. Gurholt
84Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
85Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway
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Unn K. Haukvik
84Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
86Department of Adult Psychiatry, University of Oslo, Norway
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Ingrid Agartz
97Norwegian Centre for Mental Disorders Research (NORMENT), Oslo University Hospital, Oslo, Norway
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Chadi G. Abdallah
17Clinical Neuroscience Division, National Center for PTSD, West Haven, CT, USA
52Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
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Richard Bryant
87School of Psychology, University of New South Wales, Sydney, NSW, Australia
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Judith K. Daniels
88Department of Clinical Psychology, University of Groningen, Groningen, The Netherlands
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Michael DeBellis
89Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA
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Kelene A. Fercho
18Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, USA
19Center for Brain and Behavior Research, University of South Dakota, Vermillion, SD, USA
20Sioux Falls VA Health Care System, Sioux Falls, SD, USA
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Elbert Geuze
46Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands
47Brain Research and Innovation Centre, Ministry of Defence, Utrecht, The Netherlands
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Ilan Harpaz-Rotem
17Clinical Neuroscience Division, National Center for PTSD, West Haven, CT, USA
52Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
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Julia I. Herzog
67Department of Psychosomatic Medicine and Psychotherapy, Central Institute of Mental Health Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
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Milissa L. Kaufman
37Department of Psychiatry, Harvard Medical School, Boston, MA, USA
83Division of Women’s Mental Health, McLean Hospital, Belmont, MA, USA
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Jim Lagopoulos
62University of the Sunshine Coast, Birtinya, QLD, Australia
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Ruth A. Lanius
30Department of Psychiatry, University of Western Ontario, London, ON, Canada
31Imaging Division, Lawson Health Research Institute, London, ON, Canada
90Department of Neuroscience, University of Western University, London, ON, Canada
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Katie A. McLaughlin
91Department of Psychology, Harvard University, Cambridge, MA, USA
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Sven C. Mueller
43Department of Experimental Clinical and Health Psychology, Ghent University, Belgium
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Yuval Neria
71Department of Psychiatry, Columbia University Medical Center, New York, NY, USA
72New York State Psychiatric Institute, New York, NY, USA
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Miranda Olff
35Department of Psychiatry, Amsterdam University Medical Centers, Location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
92Arq Psychotrauma Expert Group, Diemen, The Netherlands
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K. Luan Phan
42Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA
93Mental Health Service Line, Jesse Brown VA Medical Center, Chicago, IL, USA
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Martha E. Shenton
4Psychiatry Neuroimaging Laboratory, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA, USA
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Scott R. Sponheim
25Minneapolis VA Health Care System, Minneapolis, MN, USA
26Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA
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Dan J. Stein
94SAMRC Unit on Risk & Resilience in Mental Disorders, Dept of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa
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Thomas Straube
40Institute of Medical Psychology and Systems Neuroscience, University of Münster, Münster, Germany
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Nic J. A. van der Wee
75Psychiatry, LUMC, Leiden, The Netherlands
76Leiden Institute for Brain and Cognition, Leiden, The Netherlands
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Dick J. Veltman
35Department of Psychiatry, Amsterdam University Medical Centers, Location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
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Paul M. Thompson
1Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of USC, Marina del Rey, CA, USA
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Rajendra A. Morey
7Brain Imaging and Analysis Center, Duke University, Durham, NC, USA
8VISN 6 MIRECC, Durham VA, Durham, NC, USA
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Mark W. Logue
3Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
95National Center for PTSD Behavioral Sciences Division at VA Boston Healthcare System, Boston, MA, USA
96Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA
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  • Abstract
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Abstract

Background PTSD and depression commonly co-occur and have been associated with smaller hippocampal volumes compared to healthy and trauma-exposed controls. However, the hippocampus is heterogeneous, with subregions that may be uniquely affected in individuals with PTSD and depression.

Methods We used random effects regressions and a harmonized neuroimaging protocol based on FreeSurfer (v6.0) to identify sub-structural hippocampal markers of current PTSD (C-PTSD), depression, and the interaction of these conditions across 31 cohorts worldwide (N=3,115; Mage=38.9±13.9 years). Secondary analyses tested these associations by sex and after modeling the simultaneous effects of remitted PTSD, childhood trauma, mild traumatic brain injury, and alcohol use disorder.

Results A significant negative main effect of depression (n=800, vs. no depression, n=1456) was observed in the hippocampal tail (ß=−0.13) and CA1 (ß=−0.09) after adjusting for covariates and multiple testing (adjusted p’s (q)=0.028). A main effect of C-PTSD (n=1042 vs. control, n=1359) was not significant, but an interaction between C-PTSD and depression was significant in the CA1 (ß=−0.24, q=0.044). Pairwise comparisons revealed significantly smaller CA1 volumes in individuals with C-PTSD+Depression than controls (ß=−0.12, q=0.012), C-PTSD-only (ß=−0.17, q=0.001), and Depression-only (ß=−0.18, q=0.023). Follow-up analyses revealed sex effects in the hippocampal tail of depressed females, and an interaction effect of C-PTSD and depression in the fimbria of males.

Conclusions Collectively our results suggest that depression is a stronger predictor of hippocampal volumetry than PTSD, particularly in the CA1, and provide compelling evidence of more pronounced hippocampal phenotypes in comorbid PTSD and depression compared to either condition alone.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted August 21, 2019.
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Hippocampal subfield volumes are uniquely affected in PTSD and depression: International analysis of 31 cohorts from the PGC-ENIGMA PTSD Working Group
Lauren E. Salminen, Philipp G. Sämann, Yuanchao Zheng, Emily L. Dennis, Emily K. Clarke-Rubright, Neda Jahanshad, Juan E. Iglesias, Christopher D. Whelan, Steven E. Bruce, Jasmeet P. Hayes, Soraya Seedat, Christopher L. Averill, Lee A. Baugh, Jessica Bomyea, Joanna Bright, Chanellé J. Buckle, Kyle Choi, Nicholas D. Davenport, Richard J. Davidson, Maria Densmore, Seth G. Disner, Stefan du Plessis, Jeremy A. Elman, Negar Fani, Gina L. Forster, Carol E. Franz, Jessie L. Frijling, Atilla Gonenc, Staci A. Gruber, Daniel W. Grupe, Jeffrey P. Guenette, Courtney C. Haswell, David Hofmann, Michael Hollifield, Babok Hosseini, Anna R. Hudson, Jonathan Ipser, Tanja Jovanovic, Amy Kennedy-Krage, Mitzy Kennis, Anthony King, Philipp Kinzel, Saskia B. J. Koch, Inga Koerte, Sheri M. Koopowitz, Mayuresh S. Korgaonkar, William S. Kremen, John Krystal, Lauren A. M. Lebois, Ifat Levy, Michael J. Lyons, Vincent A. Magnotta, Antje Manthey, Soichiro Nakahara, Laura Nawijn, Richard W. J. Neufeld, Jack B. Nitschke, Daniel C. M. O’Doherty, Robert H. Paul, Matthew Peverill, Faisal M. Rashid, Kerry J. Ressler, Annerine Roos, Christian Schmahl, Margaret A. Sheridan, Anika Sierk, Alan N. Simmons, Jeffrey S. Simons, Raluca M. Simons, Murray B. Stein, Jennifer S. Stevens, Benjamin Suarez-Jimenez, Jean Théberge, Kathleen Thomaes, Sophia I. Thomopoulos, Leigh L. van den Heuvel, Steven J. A. van der Werff, Theo G. M. van Erp, Sanne J. H. van Rooij, Mirjam van Zuiden, Tim Varkevisser, Robert R. J. M. Vermeiren, Tor D. Wager, Henrik Walter, Xin Wang, Sherry Winternitz, Jonathan D. Wolff, Kristen Wrocklage, Xi Zhu, Christopher R. K. Ching, Tiril P. Gurholt, Unn K. Haukvik, Ingrid Agartz, Chadi G. Abdallah, Richard Bryant, Judith K. Daniels, Michael DeBellis, Kelene A. Fercho, Elbert Geuze, Ilan Harpaz-Rotem, Julia I. Herzog, Milissa L. Kaufman, Jim Lagopoulos, Ruth A. Lanius, Katie A. McLaughlin, Sven C. Mueller, Yuval Neria, Miranda Olff, K. Luan Phan, Martha E. Shenton, Scott R. Sponheim, Dan J. Stein, Thomas Straube, Nic J. A. van der Wee, Dick J. Veltman, Paul M. Thompson, Rajendra A. Morey, Mark W. Logue, for the ENIGMA-PGC-PTSD Working Group
bioRxiv 739094; doi: https://doi.org/10.1101/739094
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Hippocampal subfield volumes are uniquely affected in PTSD and depression: International analysis of 31 cohorts from the PGC-ENIGMA PTSD Working Group
Lauren E. Salminen, Philipp G. Sämann, Yuanchao Zheng, Emily L. Dennis, Emily K. Clarke-Rubright, Neda Jahanshad, Juan E. Iglesias, Christopher D. Whelan, Steven E. Bruce, Jasmeet P. Hayes, Soraya Seedat, Christopher L. Averill, Lee A. Baugh, Jessica Bomyea, Joanna Bright, Chanellé J. Buckle, Kyle Choi, Nicholas D. Davenport, Richard J. Davidson, Maria Densmore, Seth G. Disner, Stefan du Plessis, Jeremy A. Elman, Negar Fani, Gina L. Forster, Carol E. Franz, Jessie L. Frijling, Atilla Gonenc, Staci A. Gruber, Daniel W. Grupe, Jeffrey P. Guenette, Courtney C. Haswell, David Hofmann, Michael Hollifield, Babok Hosseini, Anna R. Hudson, Jonathan Ipser, Tanja Jovanovic, Amy Kennedy-Krage, Mitzy Kennis, Anthony King, Philipp Kinzel, Saskia B. J. Koch, Inga Koerte, Sheri M. Koopowitz, Mayuresh S. Korgaonkar, William S. Kremen, John Krystal, Lauren A. M. Lebois, Ifat Levy, Michael J. Lyons, Vincent A. Magnotta, Antje Manthey, Soichiro Nakahara, Laura Nawijn, Richard W. J. Neufeld, Jack B. Nitschke, Daniel C. M. O’Doherty, Robert H. Paul, Matthew Peverill, Faisal M. Rashid, Kerry J. Ressler, Annerine Roos, Christian Schmahl, Margaret A. Sheridan, Anika Sierk, Alan N. Simmons, Jeffrey S. Simons, Raluca M. Simons, Murray B. Stein, Jennifer S. Stevens, Benjamin Suarez-Jimenez, Jean Théberge, Kathleen Thomaes, Sophia I. Thomopoulos, Leigh L. van den Heuvel, Steven J. A. van der Werff, Theo G. M. van Erp, Sanne J. H. van Rooij, Mirjam van Zuiden, Tim Varkevisser, Robert R. J. M. Vermeiren, Tor D. Wager, Henrik Walter, Xin Wang, Sherry Winternitz, Jonathan D. Wolff, Kristen Wrocklage, Xi Zhu, Christopher R. K. Ching, Tiril P. Gurholt, Unn K. Haukvik, Ingrid Agartz, Chadi G. Abdallah, Richard Bryant, Judith K. Daniels, Michael DeBellis, Kelene A. Fercho, Elbert Geuze, Ilan Harpaz-Rotem, Julia I. Herzog, Milissa L. Kaufman, Jim Lagopoulos, Ruth A. Lanius, Katie A. McLaughlin, Sven C. Mueller, Yuval Neria, Miranda Olff, K. Luan Phan, Martha E. Shenton, Scott R. Sponheim, Dan J. Stein, Thomas Straube, Nic J. A. van der Wee, Dick J. Veltman, Paul M. Thompson, Rajendra A. Morey, Mark W. Logue, for the ENIGMA-PGC-PTSD Working Group
bioRxiv 739094; doi: https://doi.org/10.1101/739094

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