Newly published research highlights the significant impact of sleep disturbances on brain health in veterans diagnosed with PTSD who have also suffered mild traumatic brain injury (mTBI).

Past research has forged a strong link between sleep disturbances and both conditions. Also, PTSD and mTBI have been linked to changes in white matter microstructure in the brain. White matter consists largely of the axons that connect the brain’s neurons as well as the light-colored fatty material called myelin that insulates and protects nerve fibers. It is widely believed that white matter health, in turn, depends upon quality sleep.

A team co-led by BBRF 2009 Distinguished Investigator Martha E. Shenton, Ph.D., and Inga K. Koerte, M.D., Ph.D., both of Brigham and Women’s Hospital and Massachusetts General Hospital/Harvard Medical School, sought to determine, among other things, whether poor sleep quality itself has a “compounding” effect on alterations in white matter structure associated with mTBI and PTSD. The team’s results appeared in the Journal of Clinical Medicine, in a paper co-first authored by 2021 BBRF Young Investigator Johanna Seitz-Holland, M.D., Ph.D. and Philine Rojczyk, M.S.

Nearly one-fourth of military service members returning from deployments to Iraq and Afghanistan have been subsequently diagnosed with PTSD. Between 12% and 35% of service members sustain a mild traumatic brain injury during their deployment. The latter is thought to increase their risk of developing PTSD or exacerbating its symptoms if already present. Poor sleep quality is a hallmark symptom of PTSD and is highly prevalent following mTBI, and has been associated with more severe symptoms and slower recovery from both conditions.

Drs. Shenton, Koerte and colleagues used a type of MRI (dMRI, or diffusion-weighted MRI) to study white matter structure in a cohort of 180 veterans: 38 diagnosed with PTSD; 25 with mTBI; 94 with comorbid PTSD and mTBI; and 23 controls. In looking for the relationship between sleep quality and changes in white matter microstructure in the context of PTSD and mTBI, the team used a measure of sleep based on an 18-item self-report questionnaire. It provided measures of sleep efficiency, perceived sleep quality, and daily disturbances in sleep.

“We observed impaired sleep quality in veterans with PTSD and those with comorbid PTSD + mTBI, compared with those with mTBI only, or those without either,” the team reported. They also noted that sleep quality measures were associated with certain features of white matter microstructure, specifically in those with comorbid PTSD + mTBI. “Most important,” they said, “our findings suggest that perceived sleep quality may explain the association between PTSD symptom severity and white matter microstructure.” In sum, the team found “that sleep plays a central role in how psychological trauma affects brain health.”

Those with mTBI but no PTSD cannot be presumed to suffer psychological trauma; their trauma is physical. And in the study, the team did not see a difference in sleep quality between those with mTBI and controls who had no history of mTBI or PTSD. This is consistent with the fact that only a minority of those with mTBI experience ongoing post-concussion symptoms. In contrast, the team notes, recurrent sleep quality disturbances are still prevalent in those with PTSD even when its symptoms are in remission.

Further strengthening the association of PTSD with impaired sleep is the team’s observation that more severe PTSD symptoms corresponded with more pronounced impairments in sleep quality, efficiency, perceived quality, and daily sleep disturbances. “These results underscore that traumatic experiences [i.e., as opposed to physical brain trauma alone] might be the driving force behind sleep quality disturbances in veterans.”

Analysis of the dMRI scans suggested to the team that observed alterations in white matter microstructure associated with disturbed sleep (such as is seen in PTSD and comorbid PTSD + mTBI) may be due to impairments in the brain’s process of myelin repair. Such repair involves the clearance of brain waste products including neurotoxins such as tau and amyloid proteins (which are linked separately with the neurodegeneration seen in Alzheimer’s disease). The team stressed that the association between impaired sleep quality and abnormal white matter microstructure pertained only to veterans in the study with comorbid PTSD + mTBI.

Interestingly, it was perceived sleep quality and not necessarily sleep quality as objectively measured that appeared to negatively impact brain structure and function in the veterans. Related to “paradoxical insomnia” seen in many with PTSD, these experiences by patients of poor sleep are associated with general distress, ongoing hyperarousal states, and negative cognitive bias, the team noted. In this way, the self-perception and report of sleep quality is an important measure since it “appears to reflect overall mental wellbeing.”

The team calls for further study of what they term the “bi-directional interplay” between sleep impairments and PTSD symptom severity. Current first-line treatments for PTSD (various forms of talk therapy, stressing fear extinction) often fail to resolve sleep issues even when other PTSD symptoms are reduced. Interventions, therefore, that improve sleep quality “may simultaneously improve overall PTSD symptom severity, given that restorative sleep is needed for fear extinction and facilitates the emotional processing of traumatic events,” the researchers say. Targeting sleep disturbances “is often a necessary first step when beginning trauma therapy,” they add.

The team also included Ofer Pasternak, Ph.D., 2012 BBRF Young Investigator.