Abstract
Sleep disturbances are common in military personnel and are associated with increased risk for psychiatric morbidity, including posttraumatic stress disorder (PTSD) and depression, as well as inflammation. Improved sleep quality is linked to reductions in inflammatory bio-markers; however, the underlying mechanisms remain elusive. In this study, we examine whole genome expression changes related to improved sleep in 68 military personnel diagnosed with insomnia. Subjects were classified into the following groups and then compared: improved sleep (n = 46), or non-improved sleep (n = 22) following three months of standard of care treatment for insomnia. Within subject differential expression was determined from microarray data using the Partek Genomics Suite analysis program and the ingenuity pathway analysis (IPA) was used to determine key regulators of observed expression changes. Changes in symptoms of depression and PTSD were also compared. At baseline, both groups were similar in demographics, clinical characteristics, and gene-expression profiles. The microarray data revealed that 217 coding genes were differentially expressed at the follow-up-period compared to baseline in the participants with improved sleep. Expression of inflammatory cytokines were reduced including IL-1β, IL-6, IL-8, and IL-13, with fold changes ranging from -3.19 to -2.1, and there were increases in the expression of inflammatory regulatory genes including toll-like receptors 1, 4, 7, and 8 in the improved sleep group. IPA revealed six gene networks, including ubiquitin, which was a major regulator in these gene-expression changes. The improved sleep group also had a significant reduction in the severity of depressive symptoms. Interventions that restore sleep likely reduce the expression of inflammatory genes, which relate to ubiquitin genes and relate to reductions in depressive symptoms.
Highlights
Military personnel are often exposed to stressful conditions and erratic sleep schedules during deployment, thereby increasing their risk of developing a sleep disorder, most notably insomnia [1, 2]
Expression of inflammatory cytokines were reduced including IL1β, IL-6, interleukin 8 (IL-8), and interleukin 13 (IL-13), with fold changes ranging from −3.19 to −2.1, and there were increases in the expression of inflammatory regulatory genes including toll-like receptors 1, 4, 7, and 8 in the improved sleep group
We previously reported that posttraumatic stress disorder (PTSD), depression, and insomnia in military personnel are associated with higher concentrations of inflammatory proteins including C-reactive protein (CRP) [23], and that improved sleep resulted in reductions in inflammation [24]
Summary
Military personnel are often exposed to stressful conditions and erratic sleep schedules during deployment, thereby increasing their risk of developing a sleep disorder, most notably insomnia [1, 2]. Deployment increases the risk for psychiatric morbidity, including symptoms of posttraumatic stress disorder (PTSD) and depression, which are often comorbid with insomnia [1, 3,4,5]. Insomnia is the most common symptom for referral in military personnel returning from deployment in Operation Enduring Freedom and Operation Iraqi Freedom [3]. More than half of military personnel with sleep disturbances present with at least one other medical comorbidity, and those with insomnia are two times more likely to have PTSD [8]. There is a complex interplay between sleep quality and maintenance of physical and psychiatric health in military personnel, which likely has underlying biological foundations
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