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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Code availability
All analyses were conducted using generalizable scripts available on the ENIGMA-GitHub https://github.com/ENIGMA-git/ENIGMA/tree/master/WorkingGroups/EffectSize_and_GLM. Individual ROI level data were shared with the central site and processed using a set of R scripts with regressions customized for the current PGC-ENIGMA-PTSD dMRI analysis, publicly available on a set of Google Spreadsheet configuration files.
References
Atwoli L, Stein DJ, Koenen KC, McLaughlin KA. Epidemiology of posttraumatic stress disorder: prevalence, correlates and consequences. Curr Opin Psychiatry. 2015;28:307–11.
Fulton JJ, Calhoun PS, Wagner HR, Schry AR, Hair LP, Feeling N, et al. The prevalence of posttraumatic stress disorder in Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans: a meta-analysis. J Anxiety Disord. 2015;31:98–107.
Ferry F, Bunting B, Murphy S, O’Neill S, Stein D, Koenen K. Traumatic events and their relative PTSD burden in Northern Ireland: a consideration of the impact of the ‘Troubles’. Soc Psychiatry Psychiatr Epidemiol. 2014;49:435–46.
Galea S, Nandi A, Vlahov D. The epidemiology of post-traumatic stress disorder after disasters. Epidemiol Rev. 2005;27:78–91.
Uno H, Eisele S, Sakai A, Shelton S, Baker E, DeJesus O, et al. Neurotoxicity of glucocorticoids in the primate brain. Horm Behav. 1994;28:336–48.
Antonow-Schlorke I, Helgert A, Gey C, Coksaygan T, Schubert H, Nathanielsz PW, et al. Adverse effects of antenatal glucocorticoids on cerebral myelination in sheep. Obstet Gynecol. 2009;113:142–51.
Basser PJ, Mattiello J, LeBihan D. MR diffusion tensor spectroscopy and imaging. Biophys J. 1994;66:259–67.
Bolzenius JD, Velez CS, Lewis JD, Bigler ED, Wade BSC, Cooper DB, et al. Diffusion imaging findings in US service members with mild traumatic brain injury and posttraumatic stress disorder. J Head Trauma Rehabil. 2018;33:393–402.
Durkee CA, Sarlls JE, Hommer DW, Momenan R. White matter microstructure alterations: a study of alcoholics with and without post-traumatic stress disorder. PLoS ONE. 2013;8:e80952.
Fani N, King TZ, Jovanovic T, Glover EM, Bradley B, Choi K, et al. White matter integrity in highly traumatized adults with and without post-traumatic stress disorder. Neuropsychopharmacology. 2012;37:2740–6.
Fani N, King TZ, Shin J, Srivastava A, Brewster RC, Jovanovic T, et al. Structural and functional connectivity in posttraumatic stress disorder: associations with FKBP5. Depress Anxiety. 2016;33:300–7.
Kim SJ, Jeong D-U, Sim ME, Bae SC, Chung A, Kim MJ, et al. Asymmetrically altered integrity of cingulum bundle in posttraumatic stress disorder. Neuropsychobiology. 2006;54:120–5.
Kim MJ, Lyoo IK, Kim SJ, Sim M, Kim N, Choi N, et al. Disrupted white matter tract integrity of anterior cingulate in trauma survivors. Neuroreport. 2005;16:1049–53.
Koch SBJ, van Zuiden M, Nawijn L, Frijling JL, Veltman DJ, Olff M. Decreased uncinate fasciculus tract integrity in male and female patients with PTSD: a diffusion tensor imaging study. J Psychiatry Neurosci. 2017;42:331–42.
Lepage C, de Pierrefeu A, Koerte IK, Coleman MJ, Pasternak O, Grant G, et al. White matter abnormalities in mild traumatic brain injury with and without post-traumatic stress disorder: a subject-specific diffusion tensor imaging study. Brain Imaging Behav. 2018;12:870–81.
O’Doherty DCM, Ryder W, Paquola C, Tickell A, Chan C, Hermens DF, et al. White matter integrity alterations in post-traumatic stress disorder. Hum Brain Mapp. 2018;39:1327–38.
Olson EA, Cui J, Fukunaga R, Nickerson LD, Rauch SL, Rosso IM. Disruption of white matter structural integrity and connectivity in posttraumatic stress disorder: a TBSS and tractography study. Depress Anxiety. 2017;34:437–45.
Sanjuan PM, Thoma R, Claus ED, Mays N, Caprihan A. Reduced white matter integrity in the cingulum and anterior corona radiata in posttraumatic stress disorder in male combat veterans: a diffusion tensor imaging study. Psychiatry Res. 2013;214:260–8.
Santhanam P, Teslovich T, Wilson SH, Yeh P-H, Oakes TR, Weaver LK. Decreases in white matter integrity of ventro-limbic pathway linked to post-traumatic stress disorder in mild traumatic brain injury. J Neurotrauma. 2019;36:1093–8.
Schuff N, Zhang Y, Zhan W, Lenoci M, Ching C, Boreta L, et al. Patterns of altered cortical perfusion and diminished subcortical integrity in posttraumatic stress disorder: an MRI study. Neuroimage. 2011;54:S62–8.
Sun Y, Wang Z, Ding W, Wan J, Zhuang Z, Zhang Y, et al. Alterations in white matter microstructure as vulnerability factors and acquired signs of traffic accident-induced PTSD. PLoS ONE. 2013;8:e83473.
Sun Y-W, Hu H, Wang Y, Ding W-N, Chen X, Wan J-Q, et al. Inter-hemispheric functional and anatomical connectivity abnormalities in traffic accident-induced PTSD: a study combining fMRI and DTI. J Affect Disord. 2015;188:80–88.
Wang H-H, Zhang Z-J, Tan Q-R, Yin H, Chen Y-C, Wang H-N, et al. Psychopathological, biological, and neuroimaging characterization of posttraumatic stress disorder in survivors of a severe coalmining disaster in China. J Psychiatr Res. 2010;44:385–92.
Hu H, Zhou Y, Wang Q, Su S, Qiu Y, Ge J, et al. Association of abnormal white matter integrity in the acute phase of motor vehicle accidents with post-traumatic stress disorder. J Affect Disord. 2016;190:714–22.
Abe O, Yamasue H, Kasai K, Yamada H, Aoki S, Iwanami A, et al. Voxel-based diffusion tensor analysis reveals aberrant anterior cingulum integrity in posttraumatic stress disorder due to terrorism. Psychiatry Res. 2006;146:231–42.
Aschbacher K, Mellon SH, Wolkowitz OM, Henn-Haase C, Yehuda R, Flory JD, et al. Posttraumatic stress disorder, symptoms, and white matter abnormalities among combat-exposed veterans. Brain Imaging Behav. 2018;12:989–99.
Averill CL, Averill LA, Wrocklage KM, Scott JC, Akiki TJ, Schweinsburg B, et al. Altered white matter diffusivity of the cingulum angular bundle in posttraumatic stress disorder. Mol Neuropsychiatry. 2018;4:75–82.
Bierer LM, Ivanov I, Carpenter DM, Wong EW, Golier JA, Tang CY, et al. White matter abnormalities in Gulf War veterans with posttraumatic stress disorder: a pilot study. Psychoneuroendocrinology. 2015;51:567–76.
Davenport ND, Lim KO, Sponheim SR. White matter abnormalities associated with military PTSD in the context of blast TBI. Hum Brain Mapp. 2015;36:1053–64.
Li L, Lei D, Li L, Huang X, Suo X, Xiao F, et al. White matter abnormalities in post-traumatic stress disorder following a specific traumatic event. EBioMedicine. 2016;4:176–83.
Weis CN, Belleau EL, Pedersen WS, Miskovich TA, Larson CL. Structural connectivity of the posterior cingulum is related to reexperiencing symptoms in posttraumatic stress disorder. Chronic Stress. 2018;2. https://doi.org/10.1177/2470547018807134.
Zhang L, Zhang Y, Li L, Li Z, Li W, Ma N, et al. Different white matter abnormalities between the first-episode, treatment-naive patients with posttraumatic stress disorder and generalized anxiety disorder without comorbid conditions. J Affect Disord. 2011;133:294–9.
Dretsch MN, Lange RT, Katz JS, Goodman A, Daniel TA, Deshpande G, et al. Examining microstructural white matter in active duty soldiers with a history of mild traumatic brain injury and traumatic stress. Open Neuroimag J. 2017;11:46–57.
Maksimovskiy AL, McGlinchey RE, Fortier CB, Salat DH, Milberg WP, Oscar-Berman M. White matter and cognitive changes in veterans diagnosed with alcoholism and PTSD. J Alcohol Drug Depend. 2014;2:144.
Morey RA, Haswell CC, Selgrade ES, Massoglia D, Liu C, Weiner J, et al. Effects of chronic mild traumatic brain injury on white matter integrity in Iraq and Afghanistan war veterans. Hum Brain Mapp. 2013;34:2986–99.
Kennis M, van Rooij SJH, van den Heuvel MP, Kahn RS, Geuze E. Functional network topology associated with posttraumatic stress disorder in veterans. Neuroimage Clin. 2016;10:302–9.
Logue MW, van Rooij SJH, Dennis EL, Davis SL, Hayes JP, Stevens JS et al. Smaller hippocampal volume in posttraumatic stress disorder: a multi-site ENIGMA-PGC study. Biol Psychiatry 2018;83:244–53.
Jahanshad N, Kochunov PV, Sprooten E, Mandl RC, Nichols TE, Almasy L, et al. Multi-site genetic analysis of diffusion images and voxelwise heritability analysis: a pilot project of the ENIGMA–DTI working group. Neuroimage. 2013;81:455–69.
Kelly S, Jahanshad N, Zalesky A, Kochunov P, Agartz I, Alloza C, et al. Widespread white matter microstructural differences in schizophrenia across 4322 individuals: results from the ENIGMA Schizophrenia DTI Working Group. Mol Psychiatry. 2018;23:1261–9.
Favre P, Pauling M, Stout J, Hozer F, Sarrazin S, Abé C, et al. ENIGMA Bipolar Disorder Working Group. Widespread white matter microstructural abnormalities in bipolar disorder: evidence from mega- and meta-analyses across 3033 individuals. Neuropsychopharmacology. 2019:1–9.
Kelly S, van Velzen L, Veltman D, Thompson P, Jahanshad N, Schmaal L, et al. 941. White Matter Microstructural Differences in Major Depression: Meta-Analytic Findings from Enigma-MDD DTI. Biol Psychiatry. 2017;81:S381.
Villalon-Reina JE, Ching CRK, Kothapalli D, Sun D, Nir T, Lin A et al. Alternative diffusion anisotropy measures for the investigation of white matter alterations in 22q11.2 deletion syndrome. In: 14th International Symposium on Medical Information Processing and Analysis. International Society for Optics and Photonics, 2018, p 109750U.
Piras F, Piras F, Abe Y, Agarwal SM, Anticevic A, Ameis S, et al. White matter microstructure and its relation to clinical features of obsessive-compulsive disorder: findings from the ENIGMA OCD Working Group. BioRxiv. 2019:855916.
Asmundson GJ, Frombach I, McQuaid J, Pedrelli P, Lenox R, Stein MB. Dimensionality of posttraumatic stress symptoms: a confirmatory factor analysis of DSM-IV symptom clusters and other symptom models. Behav Res Ther. 2000;38:203–14.
Nyholt DR. A simple correction for multiple testing for single-nucleotide polymorphisms in linkage disequilibrium with each other. Am J Hum Genet. 2004;74:765–9.
Li J, Ji L. Adjusting multiple testing in multilocus analyses using the eigenvalues of a correlation matrix. Heredity. 2005;95:221–7.
Hendricks AE, Dupuis J, Logue MW, Myers RH, Lunetta KL. Correction for multiple testing in a gene region. Eur J Hum Genet. 2014;22:414–8.
Kochunov P, Williamson DE, Lancaster J, Fox P, Cornell J, Blangero J et al. Fractional anisotropy of water diffusion in cerebral white matter across the lifespan. Neurobiol Aging 2010;33:1–12.
De Bellis MD, Hooper SR, Sapia JL. Early trauma exposure and the brain. In: Vasterling JJ (ed). Neuropsychology of PTSD: Biological, cognitive, and clinical perspectives. New York, NY, US: The Guilford Press; 2005, pp 153–77.
Geibprasert S, Gallucci M, Krings T. Alcohol-induced changes in the brain as assessed by MRI and CT. Eur Radio. 2010;20:1492–501.
Pechtel P, Pizzagalli DA. Effects of early life stress on cognitive and affective function: an integrated review of human literature. Psychopharmacology. 2011;214:55–70.
Grant BF, Dawson DA, Stinson FS, Chou SP, Dufour MC, Pickering RP. The 12-month prevalence and trends in DSM-IV alcohol abuse and dependence: United States, 1991–1992 and 2001–2002. Drug Alcohol Depend. 2004;74:223–34.
Jovanovic T, Norrholm SD, Fennell JE, Keyes M, Fiallos AM, Myers KM, et al. Posttraumatic stress disorder may be associated with impaired fear inhibition: relation to symptom severity. Psychiatry Res. 2009;167:151–60.
Milad MR, Pitman RK, Ellis CB, Gold AL, Shin LM, Lasko NB, et al. Neurobiological basis of failure to recall extinction memory in posttraumatic stress disorder. Biol Psychiatry. 2009;66:1075–82.
Maller JJ, Welton T, Middione M, Callaghan FM, Rosenfeld JV, Grieve SM. Revealing the Hippocampal Connectome through Super-Resolution 1150-Direction Diffusion MRI. Sci Rep. 2019;9. https://doi.org/10.1038/s41598-018-37905-9.
Simmonds DJ, Hallquist MN, Asato M, Luna B. Developmental stages and sex differences of white matter and behavioral development through adolescence: a longitudinal diffusion tensor imaging (DTI) study. NeuroImage 2014;92:356–68.
Jin C, Qi R, Yin Y, Hu X, Duan L, Xu Q, et al. Abnormalities in whole-brain functional connectivity observed in treatment-naive post-traumatic stress disorder patients following an earthquake. Psychol Med. 2014;44:1927–36.
Miller DR, Hayes SM, Hayes JP, Spielberg JM, Lafleche G, Verfaellie M. Default mode network subsystems are differentially disrupted in posttraumatic stress disorder. Biol Psychiatry Cogn Neurosci Neuroimaging. 2017;2:363–71.
Malivoire BL, Girard TA, Patel R, Monson CM. Functional connectivity of hippocampal subregions in PTSD: relations with symptoms. BMC Psychiatry. 2018;18:129.
Fani N, King TZ, Reiser E, Binder EB, Jovanovic T, Bradley B, et al. FKBP5 genotype and structural integrity of the posterior cingulum. Neuropsychopharmacology. 2014;39:1206–13.
Rohlfing T. Incorrect ICBM-DTI-81 atlas orientation and white matter labels. Front Neurosci. 2013;7:4.
Lyon M, Welton T, Varda A, Maller JJ, Broadhouse K, Korgaonkar MS, et al. Gender-specific structural abnormalities in major depressive disorder revealed by fixel-based analysis. Neuroimage Clin. 2019;21:101668.
Chen L, Hu X, Ouyang L, He N, Liao Y, Liu Q, et al. A systematic review and meta-analysis of tract-based spatial statistics studies regarding attention-deficit/hyperactivity disorder. Neurosci Biobehav Rev. 2016;68:838–47.
Cloitre M, Stolbach BC, Herman JL, van der Kolk B, Pynoos R, Wang J, et al. A developmental approach to complex PTSD: childhood and adult cumulative trauma as predictors of symptom complexity. J Trauma Stress. 2009;22:399–408.
Hart H, Rubia K. Neuroimaging of child abuse: a critical review. Front Hum Neurosci. 2012;6:52.
Campbell DG, Felker BL, Liu C-F, Yano EM, Kirchner JE, Chan D, et al. Prevalence of depression–PTSD comorbidity: implications for clinical practice guidelines and primary care-based interventions. J Gen Intern Med. 2007;22:711–8.
Sexton CE, Mackay CE, Ebmeier KP. A systematic review of diffusion tensor imaging studies in affective disorders. Biol Psychiatry. 2009;66:814–23.
Shen X, Reus LM, Cox SR, Adams MJ, Liewald DC, Bastin ME, et al. Subcortical volume and white matter integrity abnormalities in major depressive disorder: findings from UK Biobank imaging data. Sci Rep. 2017;7:5547.
van Velzen LS, Kelly S, Isaev D, Aleman A, Aftanas LI, Bauer J et al. White matter disturbances in major depressive disorder: a coordinated analysis across 20 international cohorts in the ENIGMA MDD working group. Mol Psychiatry. 2019. https://doi.org/10.1038/s41380-019-0477-2.
Rogers JM, Read CA. Psychiatric comorbidity following traumatic brain injury. Brain Inj. 2007;21:1321–33.
Johnson VE, Stewart W, Smith DH. Axonal pathology in traumatic brain injury. Exp Neurol. 2013;246:35–43.
Dennis EL, Wilde EA, Newsome MR, Scheibel RS, Troyanskaya M, Velez C, et al. Enigma military brain injury: a coordinated meta-analysis of diffusion MRI from multiple cohorts. Proc IEEE Int Symp Biomed Imaging. 2018;2018:1386–9.
Hunsberger J, Austin DR, Henter ID, Chen G. The neurotrophic and neuroprotective effects of psychotropic agents. Dialogues Clin Neurosci. 2009;11:333.
Brown PJ, Stout RL, Mueller T. Posttraumatic stress disorder and substance abuse relapse among women: a pilot study. Psychol Addict Behav. 1996;10:124–8.
Brown PJ, Stout RL, Mueller T. Substance use disorder and posttraumatic stress disorder comorbidity: Addiction and psychiatric treatment rates. Psychol Addict Behav; 1999;13:115–22.
Cardenas VA, Greenstein D, Fouche J-P, Ferrett H, Cuzen N, Stein DJ, et al. Not lesser but greater fractional anisotropy in adolescents with alcohol use disorders. Neuroimage Clin. 2013;2:804–9.
Tapert SF, Theilmann RJ, Schweinsburg AD, Yafai S, Frank LR. Reduced fractional anisotropy in the splenium of adolescents with alcohol use disorder. Age 2003;16. https://cds.ismrm.org/ismrm-2003/2241.pdf.
Thompson P, Jahanshad N, Ching CRK, Salminen L, Thomopoulos SI, Bright J et al. ENIGMA and global neuroscience: a decade of large-scale studies of the brain in health and disease across more than 40 countries. PsyArXiv. 2019.
Gilbertson MW, Shenton ME, Ciszewski A, Kasai K, Lasko NB, Orr SP, et al. Smaller hippocampal volume predicts pathologic vulnerability to psychological trauma. Nat Neurosci. 2002;5:1242–7.
Admon R, Leykin D, Lubin G, Engert V, Andrews J, Pruessner J, et al. Stress-induced reduction in hippocampal volume and connectivity with the ventromedial prefrontal cortex are related to maladaptive responses to stressful military service. Hum Brain Mapp. 2013;34:2808–16.
Galinowski A, Miranda R, Lemaitre H, Paillère Martinot M-L, Artiges E, Vulser H, et al. Resilience and corpus callosum microstructure in adolescence. Psychol Med. 2015;45:2285–94.
Vlasova RM, Siddarth P, Krause B, Leaver AM, Laird KTSt, Cyr N, et al. Resilience and white matter integrity in geriatric depression. Am J Geriatr Psychiatry. 2018;26:874–83.
Taliaz D, Loya A, Gersner R, Haramati S, Chen A, Zangen A. Resilience to chronic stress is mediated by hippocampal brain-derived neurotrophic factor. J Neurosci. 2011;31:4475–83.
Krishnan V, Han M-H, Graham DL, Berton O, Renthal W, Russo SJ, et al. Molecular adaptations underlying susceptibility and resistance to social defeat in brain reward regions. Cell. 2007;131:391–404.
Frodl T, Schüle C, Schmitt G, Born C, Baghai T, Zill P, et al. Association of the brain-derived neurotrophic factor Val66Met polymorphism with reduced hippocampal volumes in major depression. Arch Gen Psychiatry. 2007;64:410.
Bathina S, Das UN. Brain-derived neurotrophic factor and its clinical implications. Arch Med Sci. 2015;11:1164–78.
Frodl T, Carballedo A, Fagan AJ, Lisiecka D, Ferguson Y, Meaney JF. Effects of early-life adversity on white matter diffusivity changes in patients at risk for major depression. J Psychiatry Neurosci. 2012;37:37–45.
Kochunov P, Jahanshad N, Sprooten E, Nichols TE, Mandl RC, Almasy L, et al. Multi-site study of additive genetic effects on fractional anisotropy of cerebral white matter: comparing meta and megaanalytical approaches for data pooling. Neuroimage. 2014;95:136–50.
Boedhoe PS, Schmaal L, Abe Y, Ameis SH, Arnold PD, Batistuzzo MC, et al. Distinct subcortical volume alterations in pediatric and adult OCD: a worldwide meta- and mega-analysis. Am J Psychiatry. 2017;174:60–69.
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.
Author information
Authors and Affiliations
Contributions
ELD, SGD, NF, LES, ML, EKC, NJ, and RAM wrote the initial draft, all authors reviewed and edited the manuscript. All authors contributed data to the analyses.
Corresponding author
Ethics declarations
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, Biomedisyn 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.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Rights and permissions
About this article
Cite this article
Dennis, E.L., Disner, S.G., Fani, N. et al. Altered white matter microstructural organization in posttraumatic stress disorder across 3047 adults: results from the PGC-ENIGMA PTSD consortium. Mol Psychiatry 26, 4315–4330 (2021). https://doi.org/10.1038/s41380-019-0631-x
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41380-019-0631-x
This article is cited by
-
Structural integrity of grey and white matter in schizophrenic patients by diffusion tensor imaging
Egyptian Journal of Radiology and Nuclear Medicine (2023)
-
Sex-Based Contributors to and Consequences of Post-traumatic Stress Disorder
Current Psychiatry Reports (2023)
-
Clinical anatomy of the precuneus and pathogenesis of the schizophrenia
Anatomical Science International (2023)
-
The relationship between chronic PTSD, cortical volumetry and white matter microstructure among Australian combat veterans
Military Medical Research (2022)
-
Pediatric PTSD is characterized by age- and sex-related abnormalities in structural connectivity
Neuropsychopharmacology (2021)