Study objectives

To test if posttraumatic stress disorder (PTSD) is associated with low brain gamma-aminobutyric acid (GABA) levels and if reduced GABA is mediated by poor sleep quality.

Design

Laboratory study using in vivo proton magnetic resonance spectroscopy (1H MRS) and behavioral testing.

Setting

VA Medical Center Research Service, Psychiatry and Radiology.

Patients or participants

Twenty-seven patients with PTSD (PTSD+) and 18 trauma-exposed controls without PTSD (PTSD-), recruited from United States Army reservists, Army National Guard, and mental health clinics.

Interventions

None.

Measurements and results

1H MRS at 4 Tesla yielded spectra from three cortical brain regions. In parieto-occipital and temporal cortices, PTSD+ had lower GABA concentrations than PTSD-. As expected, PTSD+ had higher depressive and anxiety symptom scores and a higher Insomnia Severity Index (ISI) score. Higher ISI correlated with lower GABA and higher glutamate levels in parieto-occipital cortex and tended to correlate with lower GABA in the anterior cingulate. The relationship between parieto-occipital GABA and PTSD diagnosis was fully mediated through insomnia severity. Lower N-acetylaspartate and glutamate concentrations in the anterior cingulate cortex correlated with higher arousal scores, whereas depressive and anxiety symptoms did generally not influence metabolite concentrations.

Conclusions

Low brain gamma-aminobutyric acid (GABA) concentration in posttraumatic stress disorder (PTSD) is consistent with most findings in panic and social anxiety disorders. Low GABA associated with poor sleep quality is consistent with the hyperarousal theory of both primary insomnia and PTSD. Our data demonstrate that poor sleep quality mediates low parieto-occipital GABA in PTSD. The findings have implications for PTSD treatment approaches.

Exposure to traumatic psychological stress increases risk for disease events and mortality in patients with cardiovascular disease (CVD). While the biological mechanisms of these effects are not known, inflammation may play a key role as it is both elevated by psychological stress and involved in the development and progression of CVD. In a prospective study of patients with stable CVD (n = 979), we examined if higher lifetime trauma exposure was associated with elevated levels of inflammation at baseline and at five-year follow-up, and with greater increases in inflammation over time. Inflammation was indexed by a composite score incorporating the inflammatory markers interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) and resistin. In follow-up analyses, we adjusted for sociodemographic factors, psychiatric disorders and health behaviors that were significantly associated with trauma exposure. Higher trauma exposure was associated with elevated inflammation at baseline (β = .09, p = .01) and at five-year follow-up (β = .09, p = .03). While levels of inflammation increased from baseline to follow-up in the sample, there was no significant association between trauma exposure and rate of change in inflammation. Findings were robust to adjustments for sociodemographic factors and psychiatric disorders, but health behaviors appeared to contribute to the association between trauma and inflammation at follow-up. This is the first large-scale demonstration of an association between lifetime trauma exposure and inflammation. High lifetime exposure to traumatic stress may contribute to an accelerated rate of CVD progression through elevated inflammation.

Study objectives

Trauma-related nightmares are highly prevalent among veterans and are associated with higher-severity insomnia and posttraumatic stress disorder. Cognitive behavioral therapy for insomnia (typically 6-8 sessions) has been shown to reduce trauma-related nightmares. Brief behavioral treatment for insomnia (BBTI, 4 sessions) has been found to be comparable to CBT-I in decreasing insomnia severity; however, the effects of BBTI on nightmares have not been investigated. The current study tested the effects of BBTI on both trauma-related nightmares and nontrauma-related bad dreams using an active control group treated using progressive muscle relaxation therapy. In addition, we tested whether baseline trauma-related nightmare frequency and baseline nontrauma-related bad dream frequency moderated changes in insomnia severity.

Methods

Participants were 91 military veterans with insomnia disorder randomized to BBTI or progressive muscle relaxation therapy. Participants reported insomnia severity on the Insomnia Severity Index and reported trauma-related nightmare frequency and nontrauma-related bad dream frequency on the Pittsburgh Sleep Quality Index-PTSD Addendum.

Results

We found that BBTI significantly reduced trauma-related nightmares from baseline to posttreatment, whereas progressive muscle relaxation therapy did not. However, reductions in trauma-related nightmares were not maintained at the 6-month follow up. Neither BBTI nor progressive muscle relaxation therapy reduced nontrauma-related bad dreams from baseline to posttreatment. We also found that neither baseline trauma-related nightmare frequency nor baseline nontrauma-related bad dream frequency moderated changes in insomnia symptom severity.

Conclusions

Findings from the current study suggest that BBTI may help reduce trauma-related nightmares. Further research is needed to better understand the potential mechanisms underlying how improved sleep may reduce trauma-related nightmares.

Clinical trial registration

Registry: ClinicalTrials.gov; Name: Brief Behavioral Insomnia Treatment Study (BBTI); URL: https://clinicaltrials.gov/ct2/show/NCT02571452; Identifier: NCT02571452.

Citation

Ranney RM, Gloria R, Metzler TJ, Huggins J, Neylan TC, Maguen S. Brief behavioral treatment for insomnia decreases trauma-related nightmare frequency in veterans. J Clin Sleep Med. 2022:18(7):1831-1839.

Study objectives

Physical inactivity is linked to health outcomes such as obesity, diabetes, and psychiatric disorders. Sleep disturbance has been linked to the same adverse outcomes. We examine the influence of sleep on physical activity as a novel approach to understand these relationships. Specifically, our objective was to determine whether low sleep quality predicts low physical activity in posttraumatic stress disorder (PTSD), a disorder associated with sleep disturbance, physical inactivity, and poor health outcomes.

Methods

We used data from the Mind Your Heart Study, a prospective cohort study of 736 outpatients recruited from two Department of Veterans Affairs (VA) medical centers. We assessed PTSD with the Clinician Administered PTSD Scale, sleep quality using an item from the Pittsburgh Sleep Quality Index, and physical activity by self-report at baseline and again one year later. Hierarchical multiple regression models and structural equation modeling were used to examine the relationships among PTSD, sleep, and physical activity.

Results

Sleep quality but not PTSD status was prospectively associated with lower physical activity in a model adjusting for age, sex, apnea probability, depression, body mass index, and baseline physical activity (β = 0.129, SE = 0.072, p < 0.01). Structural equation modeling indicated that the results were consistent with sleep quality statistically mediating the relationship between PTSD status at baseline and physical activity one year later.

Conclusions

Worse sleep quality predicts lower physical activity in PTSD, providing possible evidence for a behavioral pathway from disturbed sleep to poor physical health outcomes.

Child abuse (CA), which is linked to posttraumatic stress disorder (PTSD), has been associated with a reduction in both hippocampal and corpus callosum (CC) volume. However, few studies have explored these relationships on psychophysiological variables related to trauma exposure. Therefore, we assessed whether the interaction between CA and hippocampal and CC volume were associated with enhanced fear potentiated psychophysiological response patterns in a sample of Veterans. 147 Veteran participants who were part of a larger study of Gulf War Illness were exposed to startling sounds in no, ambiguous, and high threat conditions and also provided MRI data. The Clinician Administered PTSD Scale and Trauma History Questionnaire were used to measure PTSD and CA respectively. Psychophysiological response was measured by EMG, SCR, and heart rate. Repeated-measures mixed linear models were used to assess the significance of CA by neural structure interactions. CA interacted with both hippocampal and CC volume on psychophysiological response magnitudes, where participants with CA and smaller hippocampal volume had greater EMG (p < 0.01) and SCR (p < 0.05) magnitudes across trials and over threat conditions. Participants with CA and smaller CC volume had greater SCR magnitudes across trials and over threat conditions (p < 0.01). Hippocampal and genu volume mediated CA and psychophysiological response magnitude. CA may impact psychophysiological response via a reduction in hippocampal and CC volume. Volumetric reduction in these structures may indicate a neurofunctional, CA-related increase in threat sensitivity, which could portend increased PTSD susceptibility and adverse interpersonal and social consequences across the lifespan.

Posttraumatic stress disorder (PTSD) is associated with fear response system dysregulation. Research has shown that the anterior cingulate cortex (ACC) may modulate the fear response and that individuals with PTSD have abnormalities in ACC structure and functioning. Our objective was to assess whether ACC volume moderates the relationship between PTSD and fear-potentiated psychophysiological response in a sample of Gulf War Veterans. 142 Veteran participants who were associated with a larger study associated with Gulf War Illness were exposed to no threat, ambiguous threat, and high threat conditions in a fear conditioned startle response paradigm and also provided MRI imaging data. PTSD was assessed using the Clinician Administered PTSD Scale (CAPS). Decreased caudal ACC volume predicted greater psychophysiological responses with a slower habituation of psychophysiological magnitudes across trials (p < 0.001). PTSD diagnosis interacted significantly with both caudal and rostral ACC volumes on psychophysiological response magnitudes, where participants with PTSD and smaller rostral and caudal ACC volumes had greater psychophysiological magnitudes across trials (p < 0.05 and p < 0.001, respectively) and threat conditions (p < 0.05 and p < 0.005). Our results suggest that ACC volume may moderate both threat sensitivity and threat response via impaired habituation in individuals who have been exposed to traumatic events. More research is needed to assess whether ACC size and these associated response patterns are due to neurological processes resulting from trauma exposure or if they are indicative of a premorbid risk for PTSD subsequent to trauma exposure.

INTRODUCTION: While the BDNF Val66Met polymorphism has been linked to various psychological disorders, limited focus has been on its relationship to posttraumatic stress disorder (PTSD) and early traumas such as child abuse. Therefore, we assessed whether Val66Met was associated with fear potentiated psychophysiological response and HPA axis dysfunction and whether PTSD status or child abuse history moderated these outcomes in a sample of Veterans. METHODS: 226 and 173 participants engaged in a fear potentiated acoustic startle paradigm and a dexamethasone suppression test (DST) respectively. Fear conditions included no, ambiguous, and high threat conditions. Psychophysiological response measures included electromyogram (EMG), skin conductance response (SCR), and heart rate. The Clinician Administered PTSD Scale (CAPS) and the Trauma History Questionnaire (THQ) were used to assess PTSD status and child abuse history respectively. RESULTS: Met allele carriers exhibited greater SCR magnitudes in the no and ambiguous threat conditions (p < 0.01 and p < 0.05 respectively). Met carriers with PTSD exhibited greater physiological response magnitudes in the ambiguous (SCR, p < 0.001) and high threat conditions (SCR and heart rate, both p ≤ 0.005). Met carrier survivors of child abuse exhibited blunted heart rate magnitudes in the high threat condition (p < 0.01). Met allele carries with PTSD also exhibited greater percent cortisol suppression (p < 0.005). LIMITATIONS: Limitations included small sample size and the cross-sectional nature of the data. CONCLUSIONS: The Val66met may impact PTSD susceptibility differentially via enhanced threat sensitivity and HPA axis dysregulation. Child abuse may moderate Val66Mets impact on threat reactivity. Future research should explore how neuronal mechanisms might mediate this risk.

Disturbed sleep is a core feature of posttraumatic stress disorder (PTSD), characterized in part by decreased delta power sleep that may result from stress-related alterations in corticotropin releasing factor (CRF), hypothalamic pituitary adrenal axis (HPA) regulation and glucocorticoid signaling. Overnight HPA axis response mediating sleep disturbances in men and women with PTSD was examined using a metyrapone challenge. Metyrapone blocks cortisol synthesis, removing negative feedback, and increases the release of hypothalamic CRF and pituitary adrenocorticotropic hormone (ACTH). Laboratory-based polysomnography was used to monitor the sleep of 66 medically healthy, medication-free men and pre-menopausal follicular phase women including 33 with chronic PTSD (16 women and 17 men) and 33 age- and sex-matched controls (14 women and 19 men) over 3 consecutive nights. Participants completed an overnight metyrapone challenge after an adaptation and baseline night of sleep and ACTH was obtained by repeated blood sampling. Metyrapone resulted in a greater increase in ACTH and greater decreases in cortisol and delta spectral power sleep in PTSD subjects compared to controls, and a greater increase in ACTH in women compared to men. There was no sex difference in metyrapone effects on delta power sleep, and no significant metyrapone by PTSD by sex interactions with either ACTH or delta power sleep. Regression analyses indicated that a greater increase in ACTH response was associated with a greater decrease in delta power sleep response in PTSD subjects, but no such relationship was found in controls. The PTSD group difference was similar in men and women. These results suggest that stress-related alterations of the HPA axis in PTSD may contribute to sleep difficulties. Therapeutics that target the HPA axis may offer promise as a potential future treatment for PTSD and related sleep difficulties.

OBJECTIVES: To determine the interaction of age and habitual sleep duration in predicting cognitive performance in a large sample of participants aged 15 to 89 years. METHODS: This study is a cross-sectional analysis of performance data gathered between January 2012 and September 2013. First-time players (N = 512823) of three internet cognitive training games measuring processing speed, working memory, visuospatial memory, and arithmetic participated in the study. RESULTS: Performance was based on a measure of speed and accuracy for each game. The relationship between performance and self-reported habitual sleep duration was examined in the sample as a whole and across 10-year age groups starting at age 15 and ending at 75 and older. Performance peaked at 7 h of sleep duration for all three games in the sample as a whole, and the decrements in performance for sleep durations greater than 7 h were either comparable or greater in the youngest as compared to the oldest age groups. CONCLUSIONS: These findings challenge the hypothesis that deteriorating cognitive performance with long sleep duration is driven by medical comorbidities associated with aging. Further, these data are consistent with an optimal dose model of sleep and suggest that the model for the homeostatic recovery of cognitive function as a function of sleep duration should incorporate a curvilinear decline with longer duration sleep, indicating that there may be a cost to increased sleep. Replication and further research is essential for clarifying the sleep duration-cognition relationship in youth and adults of all ages.

A growing literature shows prominent sex effects for risk for post-traumatic stress disorder and associated medical comorbid burden. Previous research indicates that post-traumatic stress disorder is associated with reduced slow wave sleep, which may have implications for overall health, and abnormalities in rapid eye movement sleep, which have been implicated in specific post-traumatic stress disorder symptoms, but most research has been conducted in male subjects. We therefore sought to compare objective measures of sleep in male and female post-traumatic stress disorder subjects with age- and sex-matched control subjects. We used a cross-sectional, 2 × 2 design (post-traumatic stress disorder/control × female/male) involving83 medically healthy, non-medicated adults aged 19-39 years in the inpatient sleep laboratory. Visual electroencephalographic analysis demonstrated that post-traumatic stress disorder was associated with lower slow wave sleep duration (F(3,82)  = 7.63, P = 0.007) and slow wave sleep percentage (F(3,82)  = 6.11, P = 0.016). There was also a group × sex interaction effect for rapid eye movement sleep duration (F(3,82)  = 4.08, P = 0.047) and rapid eye movement sleep percentage (F(3,82)  = 4.30, P = 0.041), explained by greater rapid eye movement sleep in post-traumatic stress disorder females compared to control females, a difference not seen in male subjects. Quantitative electroencephalography analysis demonstrated that post-traumatic stress disorder was associated with lower energy in the delta spectrum (F(3,82)  = 6.79, P = 0.011) in non-rapid eye movement sleep. Slow wave sleep and delta findings were more pronounced in males. Removal of post-traumatic stress disorder subjects with comorbid major depressive disorder, who had greater post-traumatic stress disorder severity, strengthened delta effects but reduced rapid eye movement effects to non-significance. These findings support previous evidence that post-traumatic stress disorder is associated with impairment in the homeostatic function of sleep, especially in men with the disorder. These findings suggest that group × sex interaction effects on rapid eye movement may occur with more severe post-traumatic stress disorder or with post-traumatic stress disorder comorbid with major depressive disorder.