Serum Neurosteroid Levels Are Associated With Cortical Thickness in Individuals Diagnosed With Posttraumatic Stress Disorder and History of Mild Traumatic Brain Injury

Author:

Kinzel Philipp12,Marx Christine E.34,Sollmann Nico1256ORCID,Hartl Elisabeth127,Guenette Jeffrey P.18ORCID,Kaufmann David129,Bouix Sylvain1,Pasternak Ofer18,Rathi Yogesh1,Coleman Michael J.1,van der Kouwe Andre1011,Helmer Karl1011,Kilts Jason D.34,Naylor Jennifer C.34,Morey Rajendra A.3412,Shutter Lori13,Andaluz Norberto1415,Coimbra Raul16,Lang Ariel J.171819,George Mark S.2021,McAllister Thomas W.22,Zafonte Ross2324,Stein Murray B.171819,Shenton Martha E.1825,Koerte Inga K.122627

Affiliation:

1. Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

2. cBRAIN, Department of Child and Adolescent Psychiatry, Psychosomatic and Psychotherapy, Ludwig-Maximilians-Universität, Munich, Germany

3. VA Mid-Atlantic Mental Illness Research and Clinical Center (MIRECC) and Durham VA Medical Center, Durham, NC, USA

4. Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA

5. Department of Diagnostic and Interventional Neuroradiology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany

6. TUM-Neuroimaging Center, Klinikum rechts der Isar, Technische Universität München, Munich, Germany

7. Department of Neurology, Epilepsy Center, University Hospital Munich, Munich, Germany

8. Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

9. Department of Radiology, Charité Universitätsmedizin, Berlin, Germany

10. Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

11. Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, USA

12. Duke-UNC Brain Imaging and Analysis Center, Duke University, Durham, NC, USA

13. Departments of Critical Care Medicine, Neurology and Neurosurgery, UPMC Health System/University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

14. Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA

15. Mayfield Brain & Spine, Cincinnati, OH, USA

16. Department of General Surgery, Riverside University Health System Medical Center, Moreno Valley, CA, USA

17. VA San Diego Center of Excellence for Stress and Mental Health (CESAMH), San Diego, CA, USA

18. Department of Psychiatry, University of California San Diego, La Jolla, CA, USA

19. Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, USA

20. Psychiatry Department, Medical University of South Carolina, Charleston, SC, USA

21. Ralph H. Johnson VA Medical Center, Charleston, SC, USA

22. Department of Psychiatry, Indiana School of Medicine, Indianapolis, IN, USA

23. Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School, Charlestown, MA, USA

24. Department of Physical Medicine and Rehabilitation, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

25. VA Boston Healthcare System, Brockton Division, Brockton, MA, USA

26. Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

27. Graduate School of Systemic Neuroscience, Ludwig-Maximilians-Universität, Munich, Germany

Abstract

Posttraumatic stress disorder (PTSD) co-occurring with mild traumatic brain injury (mTBI) is common in veterans. Worse clinical outcome in those with PTSD has been associated with decreased serum neurosteroid levels. Furthermore, decreased cortical thickness has been associated with both PTSD and mTBI. However, it is not known whether decreased neurosteroids are associated with decreased cortical thickness in PTSD co-occurring with mTBI. This study included 141 individuals divided into the following groups: ( a) mTBI group (n = 32 [10 female, 22 male] veterans with a history of mTBI); ( b) PTSD + mTBI group (n = 41 [6 female, 35 male] veterans with current PTSD with a history of mTBI); and ( c) control group (n = 68 [35 female, 33 male] control participants), which were acquired through the Injury and Traumatic Stress (INTRuST) Clinical Consortium. Subjects underwent clinical assessment, magnetic resonance imaging at 3 T, and serum neurosteroid quantifications of allopregnanolone (ALLO) and pregnenolone (PREGN). Group differences in cortical thickness and associations between serum neurosteroid levels and cortical thickness were investigated. Cortical thickness was decreased in the PTSD + mTBI group compared with the other groups. In the PTSD + mTBI group, decreased cortical thickness was also associated with lower serum ALLO (right superior frontal cortex) and lower serum PREGN (left middle temporal and right orbitofrontal cortex). Cortical thickness in the middle temporal and orbitofrontal cortex was associated with PTSD symptom severity. There were no significant associations between neurosteroids and cortical thickness in the mTBI or control groups. Decreased cortical thickness in individuals with PTSD + mTBI is associated with decreased serum neurosteroid levels and greater PTSD symptom severity. Causality is unclear. However, future studies might investigate whether treatment with neurosteroids could counteract stress-induced neural atrophy in PTSD + mTBI by potentially preserving cortical thickness.

Funder

U.S. Department of Defense

Publisher

SAGE Publications

Subject

Neurology (clinical),Neurology,General Medicine

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