Slow dissolving of emotional distress contributes to hyperarousal.
ABSTRACT: The mechanisms underlying hyperarousal, the key symptom of insomnia, have remained elusive, hampering cause-targeted treatment. Recently, restless rapid-eye-movement (REM) sleep emerged as a robust signature of sleep in insomnia. Given the role of REM sleep in emotion regulation, we hypothesized that restless REM sleep could interfere with the overnight resolution of emotional distress, thus contributing to accumulation of arousal. Participants (n = 1,199) completed questionnaires on insomnia severity, hyperarousal, self-conscious emotional distress, and thought-like nocturnal mentation that was validated to be a specific proxy for restless REM sleep (selective fragmentation: R = 0.57, P < 0.001; eye movement density: R = 0.46, P < 0.01) in 32 polysomnographically assessed participants. The experience of distress lasting overnight increased with insomnia severity (? = 0.29, P < 10(-23)), whereas short-lasting distress did not (? = -0.02, P = 0.41). Insomnia severity was associated with hyperarousal (? = 0.47, P < 10(-63)) and with the thought-like nocturnal mentation that is specifically associated with restless REM sleep (? = 0.31, P < 10(-26)). Structural equation modeling showed that 62.4% of the association between these key characteristics of insomnia was mediated specifically by reduced overnight resolution of emotional distress. The model outperformed all alternative mediation pathways. The findings suggest that restless REM sleep reflects a process that interferes with the overnight resolution of distress. Its accumulation may promote the development of chronic hyperarousal, giving clinical relevance to the role of REM sleep in emotion regulation in insomnia, depression, and posttraumatic stress disorder.
Project description:Insomnia is considered a hyperarousal disorder, in which several psychophysiological domains including the autonomic nervous system (ANS) are over-activated, potentially contributing to increased risk for cardiovascular (CV) disease. Here, we aimed to determine whether insomnia that develops in the context of the transition to menopause (menopausal transition insomnia, MTI) is similarly characterized by autonomic arousal. We also took into account modulation of the ANS by the hormonal changes of the menstrual cycle, a factor that has not previously been considered in studies on insomnia. Twenty one women with insomnia (49.0±3y) and 25 controls (48.8±2.6 y), also in the menopausal transition, had overnight laboratory-based polysomnographic recordings, including electrocardiograph, during the follicular and/or luteal (progesterone?3ngml-1) phases of the menstrual cycle, with 21 women having recordings in both phases. Nocturnal time and frequency-domain heart rate variability (HRV) measures were calculated. Heart rate (HR) was significantly elevated (by ?4bpm) in MTI compared to controls in both follicular and luteal phases, across hours of the night, including during undisturbed periods of NREM and REM sleep (p<0.05). A higher HR tended to be associated with lower frequency- and time-domain vagal HRV indices in MTI compared with controls. In both groups, HR was significantly higher and total and high frequency HRV measures were lower in the luteal phase compared to the follicular phase (p<0.05). In addition, REM compared to NREM sleep was characterized by increased HR coupled with decreased vagal modulation and increased sympathovagal balance (p<0.01). Insomnia in the menopausal transition is characterized by nocturnal autonomic hyperarousal during both follicular and luteal phases of the menstrual cycle, which could be a factor in the etiology of MTI as well as a potential CV risk factor.
Project description:Insomnia and obstructive sleep apnoea (OSA) frequently co-occur and may be causally related through sleep fragmentation and/or hyperarousal mechanisms. Previous studies suggest that OSA treatment can improve insomnia severity. However, the effect of insomnia treatment on OSA severity has not been investigated. We performed a randomised controlled trial to investigate the effect of cognitive behavioural therapy for insomnia (CBTi) on OSA severity, controlling for potential sleep-stage and posture effects. 145 patients with comorbid insomnia (International Classification of Sleep Disorders, 3rd Edn) and untreated OSA (apnoea-hypopnoea index (AHI) ?15?events·h-1 sleep) were randomised to a four-session CBTi programme or to a no-treatment control. Overnight sleep studies were completed pre- and post-treatment to measure AHI, arousal index and sleep architecture, to investigate the effect of intervention group, time, sleep stage (N1-3 or REM) and posture (supine or nonsupine) on OSA severity. The CBTi group showed a 7.5?event·h-1 greater AHI difference (mean (95% CI) decrease 5.5 (1.3-9.7)?events·h-1, Cohen's d=0.2, from 36.4?events·h-1 pre-treatment) across sleep-stages and postures, compared to control (mean increase 2.0 (-2.0-6.1)?events·h-1, d=0.01, from 37.5?events·h-1 at pre-treatment; interaction p=0.012). Compared to control, the CBTi group also had a greater reduction in total number (mean difference 5.6 (0.6-10.6) greater overall reduction; p=0.029) and duration of nocturnal awakenings (mean difference 21.1 (2.0-40.3)?min greater reduction; p=0.031) but showed no difference in the arousal index, or sleep architecture. CBTi consolidates sleep periods and promotes a 15% decrease in OSA severity in patients with comorbid insomnia and OSA. This suggests that insomnia disorder may exacerbate OSA and provides further support for treating insomnia in the presence of comorbid OSA.
Project description:Clinical evidence suggests a potentially causal interaction between sleep and affective brain function; nearly all mood disorders display co-occurring sleep abnormalities, commonly involving rapid-eye movement (REM) sleep. Building on this clinical evidence, recent neurobiological frameworks have hypothesized a benefit of REM sleep in palliatively decreasing next-day brain reactivity to recent waking emotional experiences. Specifically, the marked suppression of central adrenergic neurotransmitters during REM (commonly implicated in arousal and stress), coupled with activation in amygdala-hippocampal networks that encode salient events, is proposed to (re)process and depotentiate previous affective experiences, decreasing their emotional intensity. In contrast, the failure of such adrenergic reduction during REM sleep has been described in anxiety disorders, indexed by persistent high-frequency electroencephalographic (EEG) activity (>30 Hz); a candidate factor contributing to hyperarousal and exaggerated amygdala reactivity. Despite these neurobiological frameworks, and their predictions, the proposed benefit of REM sleep physiology in depotentiating neural and behavioral responsivity to prior emotional events remains unknown. Here, we demonstrate that REM sleep physiology is associated with an overnight dissipation of amygdala activity in response to previous emotional experiences, altering functional connectivity and reducing next-day subjective emotionality.
Project description:This study examined the extent to which self-reported exposure to blast during deployment to Iraq and Afghanistan affects subjective and objective sleep measures in service members and veterans with and without posttraumatic stress disorder (PTSD).Seventy-one medication-free service members and veterans (mean age = 29.47 ± 5.76 years old; 85% men) completed self-report sleep measures and overnight polysomnographic studies. Four multivariate analyses of variance (MANOVAs) were conducted to examine the impact of blast exposure and PTSD on subjective sleep measures, measures of sleep continuity, non-rapid eye movement (NREM) sleep parameters, and rapid eye movement (REM) sleep parameters.There was no significant Blast × PTSD interaction on subjective sleep measures. Rather, PTSD had a main effect on insomnia severity, sleep quality, and disruptive nocturnal behaviors. There was no significant Blast × PTSD interaction, nor were there main effects of PTSD or Blast on measures of sleep continuity and NREM sleep. A significant PTSD × Blast interaction effect was found for REM fragmentation.The results suggest that, although persistent concussive symptoms following blast exposure are associated with sleep disturbances, self-reported blast exposure without concurrent symptoms does not appear to contribute to poor sleep quality, insomnia, and disruptive nocturnal disturbances beyond the effects of PTSD. Reduced REM sleep fragmentation may be a sensitive index of the synergetic effects of both psychological and physical insults.
Project description:BACKGROUND:Insomnia has been associated in cross-sectional studies with increased beta (15-35 Hz) electroencephalogram (EEG) power during nonrapid eye movement (NREM) sleep, an index of cortical hyperarousal. However, it is unknown whether this cortical hyperarousal is present before individuals with insomnia develop the disorder. To fill this gap, we examined the association of childhood sleep high-frequency EEG activity with incident insomnia symptoms (i.e., absence of insomnia symptoms in childhood but presence in adolescence). METHODS:We studied a case-control subsample of 45 children (6-11 years) from the Penn State Child Cohort, a population-based random sample of 421 children, who were followed up after 8 years as adolescents (13-20 years). We examined low-beta (15-25 Hz) and high-beta (25-35 Hz) relative power at central EEG derivations during NREM sleep and, in secondary analyses, during sleep onset latency, sleep onset, and REM sleep. Incident insomnia symptoms were defined as the absence of parent-reported difficulty falling and/or staying asleep during childhood and a self-report of these insomnia symptoms during adolescence. RESULTS:Childhood high-beta power during NREM sleep was significantly increased in children who developed insomnia symptoms in adolescence (n = 25) as compared to normal sleeping controls (n = 20; p = .03). Multivariable-adjusted logistic regression models showed that increased childhood high-beta EEG power during NREM sleep was associated with a threefold increased odds (95% CI = 1.12-7.98) of incident insomnia symptoms in adolescence. No other significant relationships were observed for other sleep/wake states or EEG frequency bands. CONCLUSIONS:Increased childhood high-frequency EEG power during NREM sleep is associated with incident insomnia symptoms in adolescence. This study indicates that cortical hyperarousal during sleep may be a premorbid neurophysiological sign of insomnia, which may mediate the increased risk of psychiatric disorders associated with insomnia.
Project description:<h4>Background</h4>Self-reported sleep quality is poor in persons with human immunodeficiency virus (PWH), but prior studies commonly used nonspecific questionnaires, investigated only single sleep disorders, or lacked human immunodeficiency virus (HIV)-negative controls. We addressed these limitations in the Pharmacokinetics and Clinical Observations in People Over Fifty (POPPY) Sleep Substudy by assessing PWH and HIV-negative controls for insomnia, restless legs syndrome (RLS), and sleep apnea (SA).<h4>Methods</h4>Previously enrolled POPPY participants coenrolled in this substudy without regard to sleep symptoms. Participants completed validated sleep assessments including the Insomnia Severity Index questionnaire, International Restless Legs Syndrome Study Group questionnaire, and in-home, wrist-worn overnight oximetry. They also completed health-related quality of life questionnaires including 36-item Short Form (SF-36) and Patient-Reported Outcomes Measurement Information System (PROMIS) sleep questionnaires.<h4>Results</h4>We enrolled 357 PWH (246?>50 years of age; 111 between 18 and 50 years) and 126 HIV-negative controls >50 years of age. Among PWH, criteria were met by 21% for insomnia, 13% for RLS, and 6% for SA. Compared with HIV-negative controls, PWH had a higher risk of insomnia (adjusted odds ratio, 5.3; 95% confidence interval, 2.2-12.9) but not RLS or SA. Compared with PWH without insomnia, those with insomnia reported significantly worse scores on all SF-36 and PROMIS components; fewer than 30% reported previous diagnosis or treatment for insomnia.<h4>Conclusions</h4>Insomnia was more common in PWH, associated with worse health-related quality of life, and frequently undiagnosed. Further research should focus on the pathogenesis of insomnia in PWH and the development of effective screening and intervention strategies for this unique population.
Project description:<h4>Study objectives</h4>The clinical importance of obstructive sleep apnea, which can be prevalent during rapid eye movement (REM) sleep, is unclear. The current study examines the effect of REM-related obstructive sleep apnea on motor memory consolidation as well as on mood states.<h4>Methods</h4>We compared performance on the motor sequence task (MST), psychomotor vigilance test (PVT), Functional Outcomes of Sleep Questionnaire, and the Profile of Mood State (POMS) survey between 3 groups: healthy controls (n = 18), REM-exclusive OSA (n = 17), and patients with OSA with respiratory events throughout REM and non-rapid eye movement (NREM) sleep (n = 18).<h4>Results</h4>As expected, performance on the MST improved overnight in the healthy control group. An improvement which was similar in magnitude was also observed in the REM-exclusive OSA group whereas patients with similar OSA during REM and NREM sleep showed reduced overnight memory consolidation. Consistent with these results, we found a correlation between overnight MST improvement and the apnea hypopnea index during NREM sleep (P = .041), but not during REM sleep (P = .424). However, patients with REM-exclusive apnea demonstrated the most negative emotions based on scoring highest on the POMS survey (P = .019).<h4>Conclusions</h4>Our results provide evidence that although apneas occurring only during REM sleep do not have an effect on the encoding and stabilization of motor sequence memories, they are deleterious for emotional health.
Project description:Insomnia has been associated with increased cardiovascular (CV) risk, which may be linked to sympathetic activation. Non-invasive overnight pulse wave analysis may be a useful tool to detect early signs of autonomic changes during sleep in insomniacs. Fifty-two participants (26 men, 37±13 years, BMI: 24±5 kg/m2, 26 insomniacs/ 26 controls) underwent overnight polysomnography with pulse oximetry and pulse wave analysis including pulse rate, vascular stiffness (pulse propagation time, PPT), and a composite cardiac risk index based on autonomic function and overnight hypoxia. We identified two subgroups of insomniacs, with and without objectively disturbed sleep (sleep efficiency SE?80%, n = 14 vs. SE>80%, n = 12), and observed increased pulse rate and vascular stiffness in insomnia cases when diagnosis was based on both, subjective and objective criteria. Both insomnia groups were associated with higher overnight pulse rate than controls (median/ IQR: low-SE (low sleep efficiency): 67/ 58-70bpm; high-SE: 66/ 63-69bpm; controls: 58/ 52-63bpm; p = 0.01). Vascular stiffness was higher (reduction of PPT) in low-SE insomniacs compared with high-SE insomniacs and controls (169/ 147-232ms; 237/ 215-254ms; 244/ 180-284ms; p = 0.01). The cardiac risk index was increased in low-SE insomniacs (0.2/ 0.0-0.7; 0.0/ 0.0-0.4; 0.0/ 0.0-0.3; p = 0.05). Our results suggest a hyperarousal state in young and otherwise healthy insomniacs during sleep. The increased pulse rate and vascular stiffness in insomniacs with low SE suggest early signs of rigid vessels and potentially, an elevated CV risk. Overnight pulse wave analysis may be feasible for CV risk assessment in insomniacs and may provide a useful tool for phenotyping insomnia in order to provide individualized therapy.
Project description:Dream experience (DE) represents a fascinating condition linked to emotional processes and the human inner world. Although the overlap between REM sleep and dreaming has been overcome, several studies point out that emotional and perceptually vivid contents are more frequent when reported upon awakenings from this sleep stage. Actually, it is well-known that REM sleep plays a pivotal role in the processing of salient and emotional waking-life experiences, strongly contributing to the emotional memory consolidation. In this vein, we highlighted that, to some extent, neuroimaging studies showed that the processes that regulate dreaming and emotional salience in sleep mentation share similar neural substrates of those controlling emotions during wakefulness. Furthermore, the research on EEG correlates of the presence/absence of DE and the results on EEG pattern related to the incorporated memories converged to assign a crucial role of REM theta oscillations in emotional re-processing. In particular, the theta activity is involved in memory processes during REM sleep as well as during the waking state, in line with the continuity hypothesis. Also, the gamma activity seems to be related to emotional processes and dream recall as well as to lucid dreams. Interestingly, similar EEG correlates of DE have been found in clinical samples when nightmares or dreams occur. Research on clinical samples revealed that promoting the rehearsal of frightening contents aimed to change them is a promising method to treat nightmares, and that lucid dreams are associated with an attenuation of nightmares. In this view, DE can defuse emotional traumatic memories when the emotional regulation and the fear extinction mechanisms are compromised by traumatic and frightening events. Finally, dreams could represent a sort of simulation of reality, providing the possibility to create a new scenario with emotional mastery elements to cope with dysphoric items included in nightmares. In addition, it could be hypothesized that the insertion of bizarre items besides traumatic memories might be functional to "impoverish" the negative charge of the experiences.
Project description:Study Objectives:Insomnia is a common sleep disorder that is associated with a range of adverse outcomes. Patients with insomnia exhibit hyperarousal in multiple domains, including an elevated metabolic rate, but specific metabolic molecular perturbations are unknown. Furthermore, objective clinical markers of insomnia are not available and current assessment of pathological extent relies on self-report. Here, we provide preliminary evidence that chronic insomnia is remarkably reflected in the periphery through detailed metabolic assessments. Methods:Serum from confirmed patients with insomnia and matched good sleepers (n = 15 per group) was sampled at high temporal resolution (every 2 hr over 48 hr). Food intake was controlled by providing hourly isocaloric snacks, and sleep architecture was assessed by overnight polysomnography. Quantitative metabolic assessments were conducted using nuclear magnetic resonance spectroscopy. Results:Global metabolic profiles differentiated patients with insomnia from healthy controls, with elevated amino acid and energy metabolites and reduced branched-chain amino acid catabolic products. Strikingly, branched-chain amino acid catabolism was found to be specifically altered during the night with ~10 per cent increased accumulation of glucose in insomnia patients. Rhythmicity analysis revealed 11 metabolites that cycled diurnally across both groups, with phase advances noted for acetone and delays for lactate and branched-chain amino acids and their products. Conclusions:These preliminary observations suggest that insomnia is associated with quantitative metabolic dysregulation and supports the hyperarousal hypothesis. Furthermore, we posit that these changes lead to a state of metabolic desynchrony in insomnia that is involved in the pathophysiology of the disorder and/or mediates its impact on health outcomes. Clinical Trials Registration:NCT01957111.