Ihori Kobayashi

Autonomic and inflammatory consequences of posttraumatic stress disorder and the link to cardiovascular disease

Stress- and anxiety-related disorders are on the rise in both military and general populations. Over the next decade, it is predicted that treatment of these conditions, in particular, posttraumatic stress disorder (PTSD), along with its associated long-term comorbidities, will challenge the health care system. Multiple organ systems are adversely affected by PTSD, and PTSD is linked to cancer, arthritis, digestive disease, and cardiovascular disease. Evidence for a strong link between PTSD and cardiovascular disease is compelling, and this review describes current clinical data linking PTSD to cardiovascular disease, via inflammation, autonomic dysfunction, and the renin-angiotensin system. Recent clinical and preclinical evidence regarding the role of the renin-angiotensin system in the extinction of fear memory and relevance in PTSD-related immune and autonomic dysfunction is also addressed.

A relationship between REM sleep measures and the duration of posttraumatic stress disorder in a young adult urban minority population

STUDY OBJECTIVE To determine relationships of polysomnographic (PSG) measures with posttraumatic stress disorder (PTSD) in a young adult, urban African American population. DESIGN Cross-sectional, clinical and laboratory evaluation. SETTING Community recruitment, evaluation in the clinical research unit of an urban University hospital. PARTICIPANTS Participants (n = 145) were Black, 59.3% female, with a mean age of 23.1 y (SD = 4.8). One hundred twenty-one participants (83.4%) met criteria for trauma exposure, the most common being nonsexual violence. Thirty-nine participants (26.9%) met full (n = 19) or subthreshold criteria (n = 20) for current PTSD, 41 (28.3%) had met lifetime PTSD criteria and were recovered, and 65 (45%) were negative for PTSD. MEASUREMENTS AND RESULTS Evaluations included the Clinician Administered PTSD Scale (CAPS) and 2 consecutive nights of overnight PSG. Analysis of variance did not reveal differences in measures of sleep duration and maintenance, percentage of sleep stages, and the latency to and duration of uninterrupted segments of rapid eye movement (REM) sleep by study group. There were significant relationships between the duration of PTSD and REM sleep percentage (r = 0.53, P = 0.001), REM segment length (r = 0.43, P = 0.006), and REM sleep latency (r = -0.34, P < 0.03) among those with current PTSD that persisted when removing cases with, or controlling for, depression. CONCLUSIONS The findings are consistent with observations in the literature of fragmented and reduced REM sleep with posttraumatic stress disorder (PTSD) relatively proximate to trauma exposure and nondisrupted or increased REM sleep with chronic PTSD. CITATION Mellman TA, Kobayashi I, Lavela J, Wilson B, Hall Brown TS. A relationship between REM sleep measures and the duration of posttraumatic stress disorder in a young adult urban minority population.

Gender Differences in Sleep During the Aftermath of Trauma and the Development of Posttraumatic Stress Disorder

Women have a greater risk of developing posttraumatic stress disorder (PTSD) after exposure to trauma. Although sleep abnormalities have been implicated in the development of PTSD, gender differences in sleep soon after a traumatic event have not been investigated. This secondary analysis examined sleep characteristics using polysomnography in 13 female and 22 male trauma patients within a month of their traumatic injuries and assessed PTSD symptoms at 2-months post-injury. Results revealed more wake after sleep onset in women who developed PTSD compared to men who developed PTSD. Women with subsequent PTSD also had less total sleep time than women without subsequent PTSD. Findings suggest possible contributions of impaired sleep maintenance to the development of PTSD in women.

Nocturnal Autonomic Balance and Sleep in PTSD and Resilience

Posttraumatic stress disorder (PTSD) has been associated with heightened nocturnal autonomic nervous system (ANS) arousal and sleep disturbances. It has been suggested that relationships between sleep and nocturnal ANS activity are influenced by insomnia; however, investigation of this relationship has been limited in PTSD. This study examined nocturnal ANS activity and its relationship to sleep in PTSD and resilience. Physically healthy young adult African Americans with current PTSD (n = 20) or who had never had PTSD despite exposure to a high-impact traumatic event (resilient, n = 18) were monitored with ambulatory electrocardiograms and actigraphy for 24-hr periods. Frequency-domain heart-rate variability measures, that is, low-frequency to high-frequency ratios (LF/HF), which index sympathetic nervous system activity, and normalized HF (nHF), which indexes parasympathetic nervous system activity were examined. Normalized HF during the time-in-bed period was lower for those with PTSD than those with resilience (p = .041). Total sleep time was strongly correlated with time-in-bed LF/HF (r = -.72) and nHF (r = .75) in the resilient group, but these were not correlated in the PTSD group. The results suggest elevated nocturnal ANS arousal and dissociation between ANS activity and total sleep time in PTSD.

Validation of the Fear of Sleep Inventory (FOSI) in an urban young adult African American sample.

The Fear of Sleep Inventory (FOSI) was developed to identify factors that contribute to sleep disturbances in individuals exposed to trauma. This investigation examined the psychometric properties of the FOSI in a sample of African American young adults residing in urban areas. A 5-factor structure was derived from an exploratory factor analysis and then verified by confirmatory factor analysis. FOSI factors were positively correlated with the severity of PTSD (rs = .30 to .58, all ps < .001) and insomnia symptoms (rs = .36 to .64, all ps < .001). Individuals with probable PTSD or insomnia had higher scores on the total FOSI and each of the factors compared to those without probable PTSD (all ps < .001; effect sizes: r = .32 to .62) or insomnia (all ps < .001; effect sizes: r = .42 to .70). These data expand the evidence that the FOSI identifies factors contributing to sleep disturbances in trauma-exposed individuals.

Expression and methylation in posttraumatic stress disorder and resilience; evidence of a role for odorant receptors

Post-traumatic stress disorder (PTSD) is a common and potentially disabling disorder that develops in 1/5 to 1/3 of people exposed to severe trauma. Twin studies indicate that genetic factors account for at least one third of the variance in the risk for developing PTSD, however, the specific role for genetic factors in the pathogenesis of PTSD is not well understood. We studied genome-wide gene expression and DNA methylation profiles in 12 participants with PTSD and 12 participants who were resilient to similar severity trauma exposure. Close to 4000 genes were differentially expressed with adjusted p<0.05, fold-change >2, with all but 3 upregulated with PTSD. Eight odorant/olfactory receptor related genes were up-regulated with PTSD as well as genes related to immune activation, the Gamma-Aminobutyric Acid A (GABAA) receptor, and vitamin D synthesis. No differences with adjusted significance for DNA methylation were found. We conclude that increased gene expression may play an important role in PTSD and this expression may not be a consequence of DNA methylation. The role of odorant receptor expression warrants independent replication.

Nocturnal autonomic nervous system activity and morning proinflammatory cytokines in young adult African Americans

Compromised sleep and increased sympathetic nervous system (SNS) activity are implicated in the pathogenesis of, and disparities in, cardiovascular disease. Parasympathetic dominance during sleep may be important for cardiovascular health. Sleep and autonomic balance influence immune activity, which impacts atherogenesis. We evaluated relationships between autonomic balance during sleep and morning levels of the immune activating cytokines, C‐reactive protein (CRP) and interleukin (IL)‐6. Ninety‐four (59 female) young adult African Americans without medical conditions and substance use disorders spent 2 consecutive nights in a clinical research unit for sleep recordings and blood drawing on awakening. Cardiac tracings from the second sleep recording were analysed for heart rate variability (HRV). Body mass index was the only non‐HRV measure correlated with cytokine levels. Indicators of SNS activity for the presleep, and first non‐rapid eye movement (REM) and REM sleep periods were correlated independently with morning IL‐6 levels. Altered autonomic balance during sleep may be a modifiable factor that influences immune activation.

Sleep and Processing of Trauma Memories.

Sleep has been implicated in learning processes that appear to underlie recovery from posttraumatic stress disorder (PTSD). The importance of quality and timing of sleep following exposure-based therapies has been suggested. The present study evaluated relationships between sleep and adaptive emotional processing following written narrative exposure (WNE) to memories of traumatic events experienced by participants with clinically significant PTSD symptoms. Participants included 21 urban-residing nontreatment-seeking adults with full or subthreshold symptoms of PTSD who completed 4 sessions of 30-min WNE with the first session either in the evening or the morning. There was a significant reduction of PTSD symptom severity after WNE sessions (partial η = .65), but there was no interaction between group assignment based on the initial sessions proximity to sleep and initial reduction of PTSD symptom severity (partial η = .01). Polysomnography following evening WNE revealed increased duration of total sleep and N2%, reduced N3%, and increased eye movement density during REM sleep compared with baseline recordings (dz = 0.65 to 1.15). Reduced N3% and increased REM density were associated with less improvement of PTSD symptoms (r = .58 & -.63). These findings suggest a relationship between preservation of diminished arousal during sleep and adaptive trauma memory processing.

Impact of Traumatic Stress on Sleep and Management Options in Women

After exposure to traumatic stress, women are at greater risk than men for developing symptoms of some psychiatric disorders, including insomnia and nightmares. Sleep disturbance is one of the most refractory symptoms of posttraumatic stress disorder. Women were included in a few studies that examined efficacy of psychological or pharmacologic interventions for trauma-related sleep disturbances. Studies demonstrated preliminary evidence for efficacy of cognitive behavioral therapy for insomnia, imagery rehearsal therapy, and combinations of these techniques in treating insomnia and nightmares in trauma-exposed women. Prazosin as an adjunct to ongoing treatment is a potentially efficacious strategy for treating trauma-related nightmares in women.