Cortical volume abnormalities in posttraumatic stress disorder: an ENIGMA-psychiatric genomics consortium PTSD workgroup mega-analysis

Abstract

Studies of posttraumatic stress disorder (PTSD) report volume abnormalities in multiple regions of the cerebral cortex. However, findings for many regions, particularly regions outside commonly studied emotion-related prefrontal, insular, and limbic regions, are inconsistent and tentative. Also, few studies address the possibility that PTSD abnormalities may be confounded by comorbid depression. A mega-analysis investigating all cortical regions in a large sample of PTSD and control subjects can potentially provide new insight into these issues. Given this perspective, our group aggregated regional volumes data of 68 cortical regions across both hemispheres from 1379 PTSD patients to 2192 controls without PTSD after data were processed by 32 international laboratories using ENIGMA standardized procedures. We examined whether regional cortical volumes were different in PTSD vs. controls, were associated with posttraumatic stress symptom (PTSS) severity, or were affected by comorbid depression. Volumes of left and right lateral orbitofrontal gyri (LOFG), left superior temporal gyrus, and right insular, lingual and superior parietal gyri were significantly smaller, on average, in PTSD patients than controls (standardized coefficients = −0.111 to −0.068, FDR corrected P values < 0.039) and were significantly negatively correlated with PTSS severity. After adjusting for depression symptoms, the PTSD findings in left and right LOFG remained significant. These findings indicate that cortical volumes in PTSD patients are smaller in prefrontal regulatory regions, as well as in broader emotion and sensory processing cortical regions.

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Fig. 1: Cortical volume differences between PTSD and control subjects.

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Acknowledgements

The individual cohorts were supported by following grants: 1R21MH102634, 5U01AA021681-08, Academic Medical Center Research Council (110614), Anonymous Women’s Health Fund, Barlow Family Fund, BOF 01J05415, CDMRP W81XWH-08–2–0038, Center for Brain and Behavior Research Pilot Grant, CX001600 VA CDA, Dana Foundation, DoD W81XWH08-2-0159, DoD W81XWH-10-1-0925, DoD W81XWH-12-2-0012, F32MH109274, German Research Foundation (DA 1222/4-1 and WA 1539/8-2), German Research Society (Deutsche Forschungsgemeinschaft, DFG; SFB/TRR 58: C06, C07), HD071982, HD085850, K01MH118428, K23MH090366-01, K24DA028773, K24MH71434, K99NS096116, Kasparian Fund, L30MH114379, M01RR00039, MH071537, MH098212, MH101380, MJFF 14848, NARSAD- Young Investigator Grant, National Institute of Child Health and Human Development (P30-HD003352), NCATS (CTSA)- Yale Center for Clinical Investigation, The Netherlands Organization for Health Research and Development (40-00812-98-10041), NHMRC Program Grant (1073041), NIAAA (P50)- Center for the Translational Neuroscience in Alcohol, P30HD003352, P41EB015922, R01AA12479, R01AG059874, R01MH043454, R01MH096987, R01MH103291, R01MH105355, R01MH105535, R01MH110483, R01MH111671, R01MH116147, R01MH117601, R01MH61744, R01MH63407, R21MH097196, R21MH098198, R21MH112956, R56AG058854, South African Medical Research Council, South Dakota Governor’s Research Center Grant, T32MH018931, Trauma Scholars Fund, U54EB020403, UCI-LBVA Biumvirate Grant, UL1TR000153, UL1TR000454, The University of Wisconsin Institute for Clinical and Translational Research, VA CSR&D 1IK2CX001680, VA Merit Review Program, VA National Center for PTSD, VA RR&D1IK2RX000709, VA RR&D1K1RX002325, VA RR&D1K2RX002922, VA RR&DI01RX000622, VISN6 MIRECC.

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Dr CGA has served as a consultant, speaker and/or on advisory boards for FSV7, Lundbeck, Psilocybin Labs, 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). Dr RJD is the founder and president of, and serves on the board of directors for, the non-profit organization Healthy Minds Innovations, Inc. Dr NJ received partial research support from Biogen, Inc. (Boston, USA) for research unrelated to the content of this paper. Dr JHK 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); filed a patent for Intranasal Administration of Ketamine to Treat Depression. U.S. Application No. 14/197,767 (filed on March 5, 2014); filed US application or Patent Cooperation Treaty international application No. 14/306,382 (filed on June 17, 2014); and filed a patent for using mTOR inhibitors to augment the effects of antidepressants (filed on August 20, 2018). Dr PMT received partial research support from Biogen, Inc. (Boston, USA) for research unrelated to the topic of this paper. No other authors reported conflicts of interest.

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Wang, X., Xie, H., Chen, T. et al. Cortical volume abnormalities in posttraumatic stress disorder: an ENIGMA-psychiatric genomics consortium PTSD workgroup mega-analysis. Mol Psychiatry (2020). https://doi.org/10.1038/s41380-020-00967-1

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