Mark W Logue1, Sanne J H van Rooij2, Emily L Dennis3, Sarah L Davis4, Jasmeet P Hayes5, Jennifer S Stevens2, Maria Densmore6, Courtney C Haswell4, Jonathan Ipser7, Saskia B J Koch8, Mayuresh Korgaonkar9, Lauren A M Lebois10, Matthew Peverill11, Justin T Baker12, Premika S W Boedhoe13, Jessie L Frijling14, Staci A Gruber12, Ilan Harpaz-Rotem15, Neda Jahanshad3, Sheri Koopowitz7, Ifat Levy16, Laura Nawijn14, Lauren O'Connor17, Miranda Olff18, David H Salat19, Margaret A Sheridan20, Jeffrey M Spielberg21, Mirjam van Zuiden14, Sherry R Winternitz12, Jonathan D Wolff10, Erika J Wolf5, Xin Wang22, Kristen Wrocklage15, Chadi G Abdallah15, Richard A Bryant23, Elbert Geuze24, Tanja Jovanovic2, Milissa L Kaufman10, Anthony P King25, John H Krystal15, Jim Lagopoulos26, Maxwell Bennett26, Ruth Lanius27, Israel Liberzon25, Regina E McGlinchey28, Katie A McLaughlin11, William P Milberg28, Mark W Miller5, Kerry J Ressler29, Dick J Veltman13, Dan J Stein7, Kathleen Thomaes13, Paul M Thompson3, Rajendra A Morey30. 1. National Center for PTSD, Behavioral Science Division, VA Boston Healthcare System, Boston, Massachusetts; Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts; Department of Biomedical Genetics, Boston University School of Medicine, Boston, Massachusetts; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts. 2. Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia. 3. Imaging Genetics Center, Mary and Mark Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine, University of Southern California, Marina del Rey, California. 4. Mid-Atlantic Mental Illness Research, Education and Clinical Center, Durham VA Medical Center, Durham, North Carolina; Duke-UNC Brain Imaging and Analysis Center, Duke University, Durham, North Carolina. 5. National Center for PTSD, Behavioral Science Division, VA Boston Healthcare System, Boston, Massachusetts; Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts. 6. Department of Psychiatry, University of Western Ontario, London, Ontario, Canada. 7. Department of Psychiatry, University of Cape Town, Cape Town, South Africa. 8. Brain Imaging Center, Academic Medical Center, Amsterdam, the Netherlands. 9. Brain Dynamics Centre, Westmead Institute for Medical Research, Sydney, Australia. 10. Department of Psychiatry, Harvard Medical School, Boston, Massachusetts; McLean Hospital, Harvard University, Belmont, Massachusetts. 11. Department of Psychology, University of Washington, Seattle, Washington. 12. McLean Hospital, Harvard University, Belmont, Massachusetts. 13. Department of Psychiatry, VU University Medical Center, Amsterdam, the Netherlands. 14. Department of Psychiatry, Academic Medical Center, Amsterdam, the Netherlands. 15. Clinical Neuroscience Division, VA National Center for PTSD, VA Connecticut HealthCare System, West Haven, Connecticut; Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut. 16. Clinical Neuroscience Division, VA National Center for PTSD, VA Connecticut HealthCare System, West Haven, Connecticut; Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut. 17. Department of Psychology, John Jay College of Criminal Justice, City University of New York, New York, New York; Graduate Center, City University of New York, New York, New York. 18. Department of Psychiatry, Academic Medical Center, Amsterdam, the Netherlands; Department of Psychiatry, Arq National Trauma Center, Diemen, the Netherlands. 19. Neuroimaging Research for Veterans Center, VA Boston Healthcare System, Boston, Massachusetts; Department of Radiology, Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts. 20. Department of Psychology and Neuroscience, University of North Carolina, Chapel Hill, North Carolina. 21. Neuroimaging Research for Veterans Center, VA Boston Healthcare System, Boston, Massachusetts; Department of Psychological and Brain Sciences, University of Delaware, Newark, Delaware. 22. Department of Psychiatry, University of Toledo, Toledo, Ohio. 23. Department of Psychology, University of New South Wales, Sydney, Australia. 24. Brain Center Rudolf Magnus, University Medical Center, Utrecht, the Netherlands. 25. Department of Psychiatry, University of Michigan, Ann Arbor, Michigan. 26. Neuroimaging Brain & Mind Research Institute, University of Sydney, Sydney, Australia. 27. National Center for PTSD, Behavioral Science Division, VA Boston Healthcare System, Boston, Massachusetts; Department of Psychiatry, University of Western Ontario, London, Ontario, Canada. 28. Translational Research Center for TBI and Stress Disorders, VA Boston Healthcare System, Boston, Massachusetts; Geriatric Research, Educational and Clinical Center, VA Boston Healthcare System, Boston, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts. 29. McLean Hospital, Harvard University, Belmont, Massachusetts; Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia. 30. Mid-Atlantic Mental Illness Research, Education and Clinical Center, Durham VA Medical Center, Durham, North Carolina; Duke-UNC Brain Imaging and Analysis Center, Duke University, Durham, North Carolina; Department of Psychiatry and Behavioral Sciences, Duke University, Durham, North Carolina. Electronic address: rajendra.morey@duke.edu.
Abstract
BACKGROUND: Many studies report smaller hippocampal and amygdala volumes in posttraumatic stress disorder (PTSD), but findings have not always been consistent. Here, we present the results of a large-scale neuroimaging consortium study on PTSD conducted by the Psychiatric Genomics Consortium (PGC)-Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) PTSD Working Group. METHODS: We analyzed neuroimaging and clinical data from 1868 subjects (794 PTSD patients) contributed by 16 cohorts, representing the largest neuroimaging study of PTSD to date. We assessed the volumes of eight subcortical structures (nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, thalamus, and lateral ventricle). We used a standardized image-analysis and quality-control pipeline established by the ENIGMA consortium. RESULTS: In a meta-analysis of all samples, we found significantly smaller hippocampi in subjects with current PTSD compared with trauma-exposed control subjects (Cohen's d = -0.17, p = .00054), and smaller amygdalae (d = -0.11, p = .025), although the amygdala finding did not survive a significance level that was Bonferroni corrected for multiple subcortical region comparisons (p < .0063). CONCLUSIONS: Our study is not subject to the biases of meta-analyses of published data, and it represents an important milestone in an ongoing collaborative effort to examine the neurobiological underpinnings of PTSD and the brain's response to trauma. Published by Elsevier Inc.
BACKGROUND: Many studies report smaller hippocampal and amygdala volumes in posttraumatic stress disorder (PTSD), but findings have not always been consistent. Here, we present the results of a large-scale neuroimaging consortium study on PTSD conducted by the Psychiatric Genomics Consortium (PGC)-Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) PTSD Working Group. METHODS: We analyzed neuroimaging and clinical data from 1868 subjects (794 PTSD patients) contributed by 16 cohorts, representing the largest neuroimaging study of PTSD to date. We assessed the volumes of eight subcortical structures (nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, thalamus, and lateral ventricle). We used a standardized image-analysis and quality-control pipeline established by the ENIGMA consortium. RESULTS: In a meta-analysis of all samples, we found significantly smaller hippocampi in subjects with current PTSD compared with trauma-exposed control subjects (Cohen's d = -0.17, p = .00054), and smaller amygdalae (d = -0.11, p = .025), although the amygdala finding did not survive a significance level that was Bonferroni corrected for multiple subcortical region comparisons (p < .0063). CONCLUSIONS: Our study is not subject to the biases of meta-analyses of published data, and it represents an important milestone in an ongoing collaborative effort to examine the neurobiological underpinnings of PTSD and the brain's response to trauma. Published by Elsevier Inc.
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