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

Philipp Kinzel; Christine E Marx; Nico Sollmann; Elisabeth Hartl; Jeffrey P Guenette; David Kaufmann; Sylvain Bouix; Ofer Pasternak; Yogesh Rathi; Michael J Coleman; Andre van der Kouwe; Karl Helmer; Jason D Kilts; Jennifer C Naylor; Rajendra A Morey; Lori Shutter; Norberto Andaluz; Raul Coimbra; Ariel J Lang; Mark S George; Thomas W McAllister; Ross Zafonte; Murray B Stein; Martha E Shenton; Inga K Koerte

doi:10.1177/1550059420909676

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

Clin EEG Neurosci. 2020 Jul;51(4):285-299. doi: 10.1177/1550059420909676. Epub 2020 Mar 18.

Authors

Philipp Kinzel^{1

2}, Christine E Marx^{3

4}, Nico Sollmann^{1

2

5

6}, Elisabeth Hartl^{1

2

7}, Jeffrey P Guenette^{1

8}, David Kaufmann^{1

2

9}, Sylvain Bouix¹, Ofer Pasternak^{1

8}, Yogesh Rathi¹, Michael J Coleman¹, Andre van der Kouwe^{10

11}, Karl Helmer^{10

11}, Jason D Kilts^{3

4}, Jennifer C Naylor^{3

4}, Rajendra A Morey^{3

4

12}, Lori Shutter¹³, Norberto Andaluz^{14

15}, Raul Coimbra¹⁶, Ariel J Lang^{17

18

19}, Mark S George^{20

21}, Thomas W McAllister²², Ross Zafonte^{23

24}, Murray B Stein^{17

18

19}, Martha E Shenton^{1

8

25}, Inga K Koerte^{1

2

26

27}

Affiliations

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.

PMID: 32186207
DOI: 10.1177/1550059420909676

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.

Keywords: cortical thickness; mild traumatic brain injury; neurosteroids; posttraumatic stress disorder.

MeSH terms

Brain Concussion*
Electroencephalography
Female
Humans
Male
Neurosteroids*
Stress Disorders, Post-Traumatic*
Veterans*

Substances

Neurosteroids