Sleep Quality Disturbances Are Associated with White Matter Alterations in Veterans with Post-Traumatic Stress Disorder and Mild Traumatic Brain Injury

Author:

Rojczyk Philine12ORCID,Seitz-Holland Johanna13ORCID,Kaufmann Elisabeth124ORCID,Sydnor Valerie J.1,Kim Cara L.12,Umminger Lisa F.12,Wiegand Tim L. T.12,Guenette Jeffrey P.15,Zhang Fan5,Rathi Yogesh15,Bouix Sylvain16ORCID,Pasternak Ofer15,Fortier Catherine B.78ORCID,Salat David7910,Hinds Sidney R.11ORCID,Heinen Florian12ORCID,O’Donnell Lauren J.5ORCID,Milberg William P.789,McGlinchey Regina E.789,Shenton Martha E.135,Koerte Inga K.12313ORCID

Affiliation:

1. Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02145, USA

2. cBRAIN, Department of Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy, Ludwig-Maximilians-University, 80336 Munich, Germany

3. Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA

4. Department of Neurology, Ludwig-Maximilians-University, 81377 Munich, Germany

5. Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA

6. Department of Software Engineering and IT, École de Technologie Supérieure, Montreal, QC H3C 1K3, Canada

7. Translational Research Center for TBI and Stress Disorders (TRACTS) and Geriatric Research, Education and Clinical Center (GRECC), VA Boston Healthcare System, Boston, MA 02130, USA

8. Department of Psychiatry, Harvard Medical School, Boston, MA 02215, USA

9. Neuroimaging Research for Veterans (NeRVe) Center, VA Boston Healthcare System, Boston, 02115 MA, USA

10. Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Department of Radiology, Boston, MA 02129, USA

11. Department of Neurology, Uniformed Services University, Bethesda, MD 20814, USA

12. Department of Pediatric Neurology and Developmental Medicine and LMU Center for Children with Medical Complexity, Dr. von Hauner Children’s Hospital, Ludwig-Maximilians-University, 80337 Munich, Germany

13. Graduate School of Systemic Neurosciences, Ludwig-Maximilians-University, 82152 Munich, Germany

Abstract

Sleep disturbances are strongly associated with mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD). PTSD and mTBI have been linked to alterations in white matter (WM) microstructure, but whether poor sleep quality has a compounding effect on WM remains largely unknown. We evaluated sleep and diffusion magnetic resonance imaging (dMRI) data from 180 male post-9/11 veterans diagnosed with (1) PTSD (n = 38), (2) mTBI (n = 25), (3) comorbid PTSD+mTBI (n = 94), and (4) a control group with neither PTSD nor mTBI (n = 23). We compared sleep quality (Pittsburgh Sleep Quality Index, PSQI) between groups using ANCOVAs and calculated regression and mediation models to assess associations between PTSD, mTBI, sleep quality, and WM. Veterans with PTSD and comorbid PTSD+mTBI reported poorer sleep quality than those with mTBI or no history of PTSD or mTBI (p = 0.012 to <0.001). Poor sleep quality was associated with abnormal WM microstructure in veterans with comorbid PTSD+mTBI (p < 0.001). Most importantly, poor sleep quality fully mediated the association between greater PTSD symptom severity and impaired WM microstructure (p < 0.001). Our findings highlight the significant impact of sleep disturbances on brain health in veterans with PTSD+mTBI, calling for sleep-targeted interventions.

Funder

VA Rehabilitation Research and Development National Network Research Center for Traumatic Brain Injury Grant

VA Merit Award

National Institute of Neurological Disorders and Stroke

National Institutes of Health Neuroimage Analysis Center

Harvard Medical School Livingston Fellowship

BBRF Young Investigator Grant

Evangelische Studienwerk Villigst

German Society for Clinical Neurophysiology and Functional Imaging

Publisher

MDPI AG

Subject

General Medicine

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