Circadian Contrasts in Heart Rate Variability Associated With Posttraumatic Stress Disorder Symptoms in a Young Adult Cohort.

Prior research has demonstrated that individuals exposed to trauma have shown impaired autonomic function. We sought to determine if heart rate variability (HRV), a marker of impaired autonomic function, differed across periods of wake, rest, and sleep as a function of the level of symptoms of posttraumatic stress disorder (PTSD). A sample of young adults (N = 209), 95 of whom met full criteria for current PTSD based on the Clinician Administered PTSD Scale (CAPS; Blake et al., 1995), were evaluated for ≈ 24 hr using actigraphy and electrocardiogram. Actigraphy data were categorized as active, rest, or sleep. Multilevel modeling analyses showed that individuals with high PTSD symptom severity had lower high-frequency HRV than individuals with low PTSD symptom severity during periods of sleep, t(1083) = 2.20, p = .028, Cohen's d = 0.12. No differences were found during periods of activity, t(1083) = 1.34, p = .499, d = 0.05, or rest, t(1083) = 1.34, p = .180, d = 0.09. Our findings extended the import of prior studies to suggest that those with elevated PTSD symptoms may have decreased parasympathetic control during sleep. Moreover, relative to periods of wake and rest, sleep may represent a state of increased vulnerability for decreased parasympathetic cardiac control. Individuals with elevated PTSD symptoms may benefit from early screening for detection of cardiovascular disease.

Aberrant nocturnal cortisol and disease progression in women with breast cancer.

While a relationship between disruption of circadian rhythms and the progression of cancer has been hypothesized in field and epidemiologic studies, it has never been unequivocally demonstrated. We determined the circadian rhythm of cortisol and sleep in women with advanced breast cancer (ABC) under the conditions necessary to allow for the precise measurement of these variables. Women with ABC (n = 97) and age-matched controls (n = 24) took part in a 24-h intensive physiological monitoring study involving polysomnographic sleep measures and high-density plasma sampling. Sleep was scored using both standard clinical metrics and power spectral analysis. Three-harmonic regression analysis and functional data analysis were used to assess the 24-h and sleep-associated patterns of plasma cortisol, respectively. The circadian pattern of plasma cortisol as described by its timing, timing relative to sleep, or amplitude was indistinguishable between women with ABC and age-matched controls (p's > 0.11, t-tests). There was, however, an aberrant spike of cortisol during the sleep of a subset of women, during which there was an eightfold increase in the amount of objectively measured wake time (p < 0.004, Wilcoxon Signed-Rank). This cortisol aberration was associated with cancer progression such that the larger the aberration, the shorter the disease-free interval (time from initial diagnosis to metastasis; r = -0.30, p = 0.004; linear regression). The same aberrant spike was present in a similar percent of women without ABC and associated with concomitant sleep disruption. A greater understanding of this sleep-related cortisol abnormality, possibly a vulnerability trait, is likely important in our understanding of individual variation in the progression of cancer.

Sleep Disturbance, Diabetes, and Cardiovascular Disease in Postmenopausal Veteran Women.

PURPOSE OF THE STUDY: To compare the prevalence and cardiometabolic health impact of sleep disturbance among postmenopausal Veteran and non-Veteran participants in the Women's Health Initiative (WHI). DESIGN AND METHODS: The prevalence of five categories of sleep disturbance--medication/alcohol use for sleep; risk for insomnia; risk for sleep disordered breathing [SDB]; risk for comorbid insomnia and SDB (insomnia + SDB); and aberrant sleep duration [SLD]--was compared in 3,707 Veterans and 141,354 non-Veterans using logistic or multinomial regression. Cox proportional hazards models were used to evaluate the association of sleep disturbance and incident cardiovascular disease (CVD) and Type 2 diabetes in Veterans and non-Veterans. RESULTS: Women Veterans were more likely to have high risk for insomnia + SDB relative to non-Veteran participants. However, prevalence of other forms of sleep disturbance was similar across groups. Baseline sleep disturbance was not differentially associated with cardiometabolic health outcomes in Veteran versus non-Veteran women. Risks for SDB and insomnia + SDB were both linked to heightened risk of CVD and diabetes; SLD was consistently linked with greater risk of CVD and diabetes in non-Veterans but less strongly and consistently in Veterans. IMPLICATIONS: Efforts to identify and treat sleep disturbances in postmenopausal women are needed and may positively contribute to the attenuation of cardiometabolic morbidity risk. Increased awareness of women Veterans' vulnerability to postmenopausal insomnia + SDB may be particularly important for health care providers who treat this population.

The Relationship Between Posttraumatic Stress Symptoms and Physical Health in a Survey of U.S. Veterans of the Iraq and Afghanistan Era.

BACKGROUND: Although a large body of literature has linked posttraumatic stress disorder (PTSD) with poor physical health among older veterans, less is known regarding the association between PTSD and health among relatively younger cohorts of veterans. OBJECTIVE: The current study examined the association between PTSD and self-reported health among a sample of veterans who served in the recent conflicts in Iraq and Afghanistan. METHOD: Veterans (N = 1030) who served in the wars in Iraq and Afghanistan completed measures of PTSD symptom severity and self-rated health between September 2009 and February 2010. Analyses examined the association between PTSD symptoms and health outcomes. RESULTS: In analyses adjusted for age, sex, race, and combat exposure, PTSD symptom severity was positively related to the number of health conditions and health symptoms reported (ps<0.001). Additionally, in analyses adjusted for age, sex, race, combat exposure, number of health conditions, and number of health symptoms, PTSD symptom severity was associated with an increased likelihood of rating one's health as poor or fair and an increased likelihood of reporting that one's physical health limits participation in activities (ps<0.001). CONCLUSION: These findings suggest that, consistent with previous research, PTSD symptom severity has a broad negative effect on physical health among veterans of the Iraq and Afghanistan era. Health promotion among veterans with PTSD may help attenuate risk of physical health consequences.

DSM-5 posttraumatic stress disorder: factor structure and rates of diagnosis.

Posttraumatic stress disorder (PTSD) is a significant problem among Iraq/Afghanistan-era veterans. To date, however, there has been only limited research on how the recent changes in DSM-5 influence the prevalence and factor structure of PTSD. To address this key issue, the present research used a modified version of a gold-standard clinical interview to assess PTSD among a large sample of Iraq/Afghanistan-era veterans (N = 414). Thirty-seven percent of the sample met DSM-5 criteria for PTSD compared to a rate of 38% when DSM-IV diagnostic criteria were used. Differences in rates of diagnosis between DSM-IV and DSM-5 were primarily attributable to changes to Criterion A and the separation of the "avoidance" and "numbing" symptoms into separate clusters. Confirmatory factor analysis (CFA) was used to compare the fit of the previous 3-factor DSM-IV model of PTSD to the 4-factor model specified in DSM-5, a 4-factor "dysphoria" model, and a 5-factor model. CFA demonstrated that the 5-factor model (re-experiencing, active avoidance, emotional numbing, dysphoric arousal, anxious arousal) provided the best overall fit to the data, although substantial support was also found for the 4-factor DSM-5 model. Low factor loadings were noted for two of the symptoms in the DSM-5 model (psychogenic amnesia and reckless/self-destructive behavior), raising questions regarding the adequacy of fit between these symptoms and the other core features of PTSD. Overall, findings suggest the DSM-5 model of PTSD is an improvement over the previous DSM-IV model of PTSD, but still may not represent the true underlying factor structure of PTSD.

Posttraumatic stress, heart rate variability, and the mediating role of behavioral health risks.

OBJECTIVE: Posttraumatic stress disorder (PTSD) has been linked to reduced heart rate variability (HRV), which is in turn a risk factor for cardiovascular disease and death. Although hyperarousal and anxiety are thought to underlie this association, behavioral health risks, including smoking, alcohol dependence, obesity, and sleep disturbance, represent potential mechanisms linking PTSD and HRV. METHODS: To test this hypothesis, short-term laboratory-based and 24-hour ambulatory measures of HRV were collected from 227 young adults (18-39 years), 107 of whom were diagnosed as having PTSD. Latent variable modeling was used to assess the relationship of PTSD symptoms with HRV along with potential behavioral health mediators. RESULTS: PTSD symptoms were associated with reduced HRV (ß = -0.21, p = .002). However, this association was reduced in models that adjusted for cigarette consumption and history of alcohol dependence and was rendered nonsignificant in a model adjusting for sleep disturbance. Independent mediation effects were deemed significant via bootstrapping analysis. Together, the three behavioral health factors (cigarette consumption, history of alcohol dependence, and sleep disturbance) accounted for 94% of the shared variance between PTSD symptoms and HRV. Abdominal obesity was not a significant mediator. CONCLUSIONS: These results indicate that behavioral factors-specifically smoking, alcohol overuse, and sleep disturbance-mediate the association between PTSD and HRV-based indices of autonomic nervous system dysregulation. Benefits from psychiatric and psychological interventions in PTSD may therefore be enhanced by including modification of health behaviors.

Demand and modality of directed attention modulate "pre-attentive" sensory processes in schizophrenia patients and nonpsychiatric controls.

BACKGROUND: Mismatch negativity (MNN) and P3a are event related potential (ERP) measures of early sensory information processing. These components are usually conceptualized as being "pre-attentive" and therefore immune to changes with variations in attentional functioning. This study aimed to determine whether manipulations of attention influence the amplitudes and latencies of MMN and P3a and, if so, the extent to which these early sensory processes govern concurrent behavioral vigilance performance in schizophrenia patients and normal subjects. METHODS: Schizophrenia patients (SZ; n = 20) and Nonpsychiatric Control Subjects (NCS; n = 20) underwent auditory ERP testing to assess MMN and P3a across 4 EEG recording sessions in which attentional demand (low vs. high) and sensory modality of directed attention (visual vs. auditory) were experimentally varied. RESULTS: Across conditions, SZ patients exhibited deficits in MMN and P3a amplitudes. Significant amplitude and latency modulation were observed in both SZ and NCS but there were no group-by-condition interactions. The amount of MMN amplitude attenuation from low- to high-demand tasks was significantly associated with increased vigilance performance in both SZ and NCS groups (r = -0.67 and r = -0.60). Several other robust associations were also observed among neurophysiologic, clinical and cognitive variables. CONCLUSIONS: Attentional demand and modality of directed attention significantly influence the amplitude and latencies of "pre-attentive" ERP components in both SZ and NCS. Deficits in MMN and P3a were not "normalized" when attention was directed to the auditory stimuli in schizophrenia patients. The adaptive modulation of early sensory information processing appears to govern concurrent attentional task performance. The temporal window reflecting automatic sensory discrimination as indexed as MMN and P3a may serve as a gateway to some higher order cognitive operations necessary for psychosocial functioning.

Relationship of menopausal status and climacteric symptoms to sleep in women undergoing chemotherapy.

GOALS OF WORK: The goal of this study was to examine the relationship between menopausal symptoms, sleep quality, and mood as measured by actigraphy and self-report prior to treatment and at the end of four cycles of chemotherapy in women with breast cancer. PATIENTS AND METHODS: Data on sleep quality (measured using actigraphy and self-report) and mood were collected prior to treatment and 12 weeks later at the end of four cycles of chemotherapy in 69 women with newly diagnosed breast cancer. In addition, each filled out the Greene Climacteric Scale. Based on reported occurrence of menses, participants were categorized post hoc into three menopausal status groups: pre-menopausal before and after chemotherapy (Pre-Pre), pre-menopausal or peri-menopausal before and peri-menopausal after chemotherapy (Pre/Peri-Peri), and post-menopausal before and after chemotherapy (Post-Post). MAIN RESULTS: Results suggested that women within the Pre-Pre group evidenced more fragmented sleep with less total sleep time (TST) after chemotherapy compared to baseline. Compared to the other groups, the Pre-Pre group also experienced less TST and more awakenings before and after chemotherapy. Although the Pre/Peri-Peri group evidenced a greater increase in vasomotor symptoms after chemotherapy, there was no relationship with sleep. All groups evidenced more depressive symptoms after chemotherapy, but depression was not related to measures of sleep. CONCLUSIONS: Contrary to the study hypothesis, these results suggest that women who are pre-menopausal or having regular menses before and after four cycles of chemotherapy have worse sleep following chemotherapy. Those women who maintain or become peri-menopausal (irregular menses) experience an increase in climacteric symptoms but do not experience an associated worsening of sleep. These results are preliminary and more research is necessary to further explain these findings.

Breast cancer patients have progressively impaired sleep-wake activity rhythms during chemotherapy.

PURPOSE: Prior cross-sectional studies have shown that cancer patients have sleep-wake activity cycles that show little distinction between daytime and nighttime, a pattern indicative of circadian disruption. This pattern is seen both before and during cancer treatment. Long-term data are needed, however, to assess to what extent circadian rhythm impairments evolve over the course of chemotherapy. The goal of this study was to assess the longitudinal course of sleep-wake activity rhythms before and during chemotherapy for breast cancer. PATIENTS AND METHODS: Ninety-five women scheduled to receive neoadjuvant or adjuvant anthracycline based chemotherapy for a stage I-III breast cancer participated. The participants wore a wrist actigraph for 72 consecutive hours at baseline (pre-chemotherapy), as well as during the weeks 1, 2 and 3 (W1, W2, W3) of cycle 1 and cycle 4 of chemotherapy. Sleep-wake circadian activity variables were computed based on actigraphic data. RESULTS: Compared to baseline, with the exception of acrophase, all circadian rhythm variables examined, including amplitude, mesor, up-mesor, down-mesor, and rhythmicity were significantly impaired during the first week of both chemotherapy cycles. Although the circadian variables approached baseline values during W2 and W3 of cycle 1, most remained significantly more impaired during W2 and W3 of cycle 4. CONCLUSION: These data suggest that the first administration of chemotherapy is associated with transient disruption of sleep-wake rhythm, while repeated administration of chemotherapy results in progressively worse and more enduring impairments in sleep-wake activity rhythms.