Decreased Delta/Beta ratio index as the sleep state-independent electrophysiological signature of sleep state misperception in Insomnia disorder: A focus on the sleep onset and the whole night.

PURPOSE: Sleep State Misperception (SSM) is described as the tendency of Insomnia Disorder (ID) patients to overestimate Sleep Latency (SL) and underestimate Total Sleep Time (TST). Literature exploring topographical components in ID with SSM is scarce and does not allow us to fully understand the potential mechanisms underlying this phenomenon. This study aims to evaluate the existence of sleep EEG topography alterations in ID patients associated with SSM compared to Healthy Controls (HC), focusing on two distinct periods: the Sleep Onset (SO) and the whole night. METHODS: Twenty ID patients (mean age: 43.5 ± 12.7; 7 M/13F) and 18 HCs (mean age: 41.6 ± 11.9; 8 M/10F) underwent a night of Polysomnography (PSG) and completed sleep diaries the following morning upon awakening. Two SSM indices, referring to the misperception of SL (SLm) and TST (TSTm), were calculated by comparing objective and subjective sleep indices extracted by PSG and sleep diary. According to these indices, the entire sample was split into 4 sub-groups: ID +SLm vs HC -SLm; ID +TSTm vs HC -TSTm. RESULTS: Considering the SO, the two-way mixed-design ANOVA showed a significant main effect of Groups pointing to a decreased delta/beta ratio in the whole scalp topography. Moreover, we found a significant interaction effect for the sigma and beta bands. Post Hoc tests showed higher sigma and beta power in anterior and temporo-parietal sites during the SO period in IDs +SLm compared to HC -SLm. Considering the whole night, the unpaired t-test revealed in IDs +TSTm significantly lower delta power during NREM, and lower delta/beta ratio index during NREM and REM sleep compared to HCs -TSTm. Finally, we found diffuse significant negative correlations between SSM indices and the delta/beta ratio during SO, NREM, and REM sleep. CONCLUSION: The main finding of the present study suggests that higher SL overestimation and TST underestimation are both phenomena related to diffuse cortical hyperarousal interpreted as a sleep state-independent electrophysiological correlate of the SSM, both during the SO and the whole night.

Hyperarousal features in the sleep architecture of individuals with and without insomnia.

Sleep architecture encodes relevant information on the structure of sleep and has been used to assess hyperarousal in insomnia. This study investigated whether polysomnography-derived sleep architecture displays signs of hyperarousal in individuals with insomnia compared with individuals without insomnia. Data from Phase 3 clinical trials, private clinics and a cohort study were analysed. A comprehensive set of sleep architecture features previously associated with hyperarousal were retrospectively analysed focusing on sleep-wake transition probabilities, electroencephalographic spectra and sleep spindles, and enriched with a novel machine learning algorithm called the Wake Electroencephalographic Similarity Index. This analysis included 1710 individuals with insomnia and 1455 individuals without insomnia. Results indicate that individuals with insomnia had a higher likelihood of waking from all sleep stages, and showed increased relative alpha during Wake and N1 sleep and increased theta power during Wake when compared with individuals without insomnia. Relative delta power was decreased and Wake Electroencephalographic Similarity Index scores were elevated across all sleep stages except N3, suggesting more wake-like activity during these stages in individuals with insomnia. Additionally, sleep spindle density was decreased, and spindle dispersion was increased in individuals with insomnia. These findings suggest that insomnia is characterized by a dysfunction in sleep quality with a continuous hyperarousal, evidenced by changes in sleep-wake architecture.

The utility of wearable headband electroencephalography and pulse photoplethysmography to assess cortical and physiological arousal in individuals with stress-related mental disorders.

Several stress-related mental disorders are characterised by disturbed sleep, but objective sleep biomarkers are not routinely examined in psychiatric patients. We examined the use of wearable-based sleep biomarkers in a psychiatric sample with headband electroencephalography (EEG) including pulse photoplethysmography (PPG), with an additional focus on microstructural elements as especially the shift from low to high frequencies appears relevant for several stress-related mental disorders. We analysed 371 nights of sufficient quality from 83 healthy participants and those with a confirmed stress-related mental disorder (anxiety-affective spectrum). The median value of macrostructural, microstructural (spectral slope fitting), and heart rate variables was calculated across nights and analysed at the individual level (N = 83). The headbands were accepted well by patients and the data quality was sufficient for most nights. The macrostructural analyses revealed trends for significance regarding sleep continuity but not sleep depth variables. The spectral analyses yielded no between-group differences except for a group × age interaction, with the normal age-related decline in the low versus high frequency power ratio flattening in the patient group. The PPG analyses showed that the mean heart rate was higher in the patient group in pre-sleep epochs, a difference that reduced during sleep and dissipated at wakefulness. Wearable devices that record EEG and/or PPG could be used over multiple nights to assess sleep fragmentation, spectral balance, and sympathetic drive throughout the sleep-wake cycle in patients with stress-related mental disorders and healthy controls, although macrostructural and spectral markers did not differ between the two groups.

Pudendal nerve blockade for persistent genital arousal disorder (PGAD): A clinical review and case report.

BACKGROUND: Persistent genital arousal disorder (PGAD) is a condition characterized by unwanted and potentially painful genital sensations or spontaneous orgasms without stimulation. We present a case of a 55-year-old woman with refractory genital arousal disorder that was treated with serial pudendal nerve blocks. CASE: RW is a 55-year-old woman with chronic pelvic pain, pudendal neuralgia, MDD, SI, GAD, CRPS, and persistent genital arousal disorder for 11 years. Her PGAD was refractory to conservative management, physical therapy, and bilateral clitoral artery embolization. We performed bilateral pudendal nerve blocks with Kenalog and Bupivacaine, which provided almost complete relief for 2-3 months. We performed a bilateral pudendal nerve radiofrequency ablation; however, there was minimal benefit. RW continues to have significant relief with serial pudendal nerve blocks. SUMMARY AND CONCLUSION: Persistent genital arousal disorder is often refractory to medication and physical therapy requiring significant intervention such as entrapment surgery or artery embolization. Our case demonstrates pudendal nerve blocks as a potential treatment modality with minimal side effects.

Hyperarousal in insomnia disorder: Current evidence and potential mechanisms.

Insomnia disorder is among the most frequent mental disorders, making research on its aetiology and pathophysiology particularly important. A unifying element of many aetiological and pathophysiological models is that they support or even centre on the role of some form of hyperarousal. In this theoretical review, we aim to summarise the current evidence on hyperarousal in insomnia. Hyperarousal is discussed as a state of relatively increased arousal in physiological, cortical and cognitive-emotional domains. Regarding physiological hyperarousal, there is no conclusive evidence for the involvement of autonomous variables such as heart rate and heart rate variability, whereas recent evidence points to a pathophysiological role of neuroendocrine variables. In addition, current literature supports a central involvement of cortical arousal, that is, high-frequency electroencephalographic activity. An increasingly important focus in the literature is on the role of other microstructural sleep parameters, especially the existence of microarousals during sleep. Beyond that, a broad range of evidence exists supporting the role of cognitive-emotional hyperarousal in the form of insomnia-related thought and worries, and their concomitant emotional symptoms. Besides being a state marker of insomnia, hyperarousal is considered crucial for the predisposition to insomnia and for the development of comorbid mental disorders. Thus, beyond presenting evidence from cross-sectional studies on markers of hyperarousal in insomnia, hypotheses about the mechanisms of hyperarousal are presented. Nevertheless, longitudinal studies are needed to further elucidate the mechanism of hyperarousal throughout the course of the disorder, and future studies should also focus on similarities and differences in hyperarousal across different diagnostic entities.

The effects of a sleep robot intervention on sleep, depression and anxiety in adults with insomnia-A randomized waitlist-controlled trial.

The study objective was to assess if a 3-week intervention with the Somnox sleep robot had effects on symptoms of insomnia, somatic arousal, and/or concurrent symptoms of depression and anxiety in adults with insomnia, compared with a waitlist-control group. The participants (n = 44) were randomized to a 3-week intervention with the sleep robot (n = 22), or to a waitlist-control group (n = 22). The primary outcome measure was the Insomnia Severity Index administered at baseline, mid-intervention, post-intervention and at 1-month follow-up. Secondary outcome measures were the Pre-Sleep Arousal Scale, and the Hospital Anxiety and Depression Scale. Additionally, sleep-onset latency, wake time after sleep onset, total sleep time and sleep efficiency were measured the week prior to and the last week of the intervention, both subjectively with the Consensus Sleep Diary and objectively with wrist actigraphy. Mixed-effects models were used to analyse data. The effect of the sleep robot on the participants' insomnia severity was not statistically significant. The differences between the intervention group and the control group on the measures of arousal, anxiety and depression were also not statistically significant, and neither were the sleep diary and actigraphy variables. In conclusion, a 3-week intervention with daily at-home use of the robot was not found to be an effective method to relieve the symptom burden in adults with insomnia.

Current models of insomnia disorder: a theoretical review on the potential role of the orexinergic pathway with implications for insomnia treatment.

Insomnia disorder is considered as a stress-related disorder associated with hyperarousal, stress and emotion dysregulation and the instability of the 'flip-flop' switch system. The orexinergic system is well known for its key role in sleep and arousal processes but also in the allostatic system regulating stress and emotions and may thus be of major interest for insomnia and its treatment. Accordingly, we discuss the potential role of orexins on sleep processes, brain systems modulating stress and emotions with potential implications for insomnia pathophysiology. We reviewed available data on the effect of dual orexin receptor antagonists (DORAs) on sleep and brain systems modulating stress/emotions with implications for insomnia treatment. We present our findings as a narrative review. Few data in animals and humans have reported that disrupted sleep and insomnia may be related to the overactivation of orexinergic system, while some more consistent data in humans and animals reported the overactivation of orexins in response to acute stress and in stress-related disorders. Taken together these findings may let us hypothesise that an orexins overactivation may be associated with stress-related hyperarousal and the hyperactivation of arousal-promoting systems in insomnia. On the other hand, it is possible that by rebalancing orexins with DORAs we may regulate both sleep and allostatic systems, in turn, contributing to a 'switch off' of hyperarousal in insomnia. Nevertheless, more studies are needed to clarify the role of the orexin system in insomnia and to evaluate the effects of DORAs on sleep, stress and emotions regulating systems.

Challenging subjective excessive daytime sleepiness as an insomnia symptom: a retrospective study.

Diagnostic manuals describe insomnia disorder (ID) characterised by fatigue and sleepiness as diurnal consequences of nocturnal symptoms. However, patients with ID do not frequently report sleepiness in the clinical setting. The present study aimed to investigate subjective sleepiness in ID measured through the Epworth Sleepiness Scale (ESS) and its independence towards daytime functioning and fatigue, and to evaluate cognitive behavioural therapy for insomnia (CBT-I) improvement in daytime consequences and their relationship to sleepiness and fatigue. We retrospectively collected the ESS evaluation in a large sample of 105 healthy controls (HCs), 671 patients with ID, and 602 patients with sleep disorders characterised by excessive daytime sleepiness (EDS). Moreover, we conducted a pre-post evaluation of the ESS in a sub-sample of patients with ID who underwent CBT-I. Component 2 of the Insomnia Severity Index and Profile of Mood States-Fatigue Inertia Scale was used to evaluate daytime functioning and fatigue. Patients with ID reported ESS levels comparable to that observed in HCs and significantly lower than the EDS group. No significant correlation arose between ESS and the diurnal impact of the disorder, suggesting the independence between daytime functioning and sleepiness in ID. Contrarily, insomnia severity and diurnal impact significantly correlated with fatigue. Data showed a statistically significant increase in sleepiness after CBT-I, despite significantly improving daytime consequences and fatigue. Although diagnostic manuals report sleepiness and fatigue as daytime consequences of sleep symptoms in patients with ID, these retrospective data indicate a dissociation between these entities. This evidence aligns with the core feature of ID: the hyperarousal status that pervades patients also during wakefulness.

Symptom dynamics among nightmare sufferers: An intensive longitudinal study.

Nightmares are considerably prevalent in the general population and are known to be closely associated with a variety of mental disorders. However, not much is known about the immediate antecedents and consequences of nightmares. Therefore, we used intensive longitudinal assessments to investigate the night-to-night within-person associations between nightmares on the one hand and fear of sleep, somatic as well as cognitive pre-sleep arousal, and sleep quality on the other hand. Young women with regular nightmares (n = 16) maintained a sleep diary for around 30 days; upon awaking, the participants reported on nightmares and sleep quality during the past night as well as the pre-sleep levels of arousal and fear of sleep (which resulted in 461 observations). Participants also wore an actigraph, which provided objective sleep parameters. Multilevel modeling showed that higher levels of fear of sleep and lower subjective sleep quality were significantly associated with higher levels of nightmare distress. Furthermore, we found individual differences in the strength of these associations, which implies that factors proximate to nightmares may vary across individuals. Pre-sleep arousal, however, did not show expected within-person associations with nightmares or fear of sleep. These findings highlight the crucial role of fear of sleep in the etiology of nightmares and sleep disturbances, while pointing to the importance of pursuing individual, personalised models that explain heterogeneity in the process of triggering nightmares.

On the relationship between EEG spectral analysis and pre-sleep cognitive arousal in insomnia disorder: towards an integrated model of cognitive and cortical arousal.

According to the hyperarousal model, insomnia is characterised by increased arousal in the cortical, cognitive, and physiological domains. However, the interaction between these arousal domains is poorly understood. The present observational case-control study aimed to investigate cortical arousal during the night, pre-sleep cognitive arousal and the relationship between these two domains. A total of 109 patients with insomnia disorder (ID) and 109 age-and gender matched healthy controls were investigated on two sleep laboratory nights. Electroencephalographic (EEG) spectral power during non-rapid eye movement (NREM) and REM sleep was analysed as a measure of cortical arousal. In addition, patients completed the Pre-Sleep Arousal Scale (PSAS), which consists of two subscales, one for cognitive arousal (PSAS-CA) and one for self-reported somatic arousal (PSAS-SA). The relationship between the subscale scores and EEG spectral power was calculated by multi- and univariate analyses of variance. During NREM and REM sleep, patients with ID showed significantly increased spectral power in the EEG gamma band. In addition, patients with ID showed significantly increased scores on both subscales of the PSAS. The PSAS-CA score was significantly associated with increased NREM and REM gamma power, whereas PSAS-SA was associated with decreases in NREM and REM gamma power. Consistent with our hypothesis, patients with ID showed increased cortical and cognitive arousal. Moreover, there was an association between these two arousal domains, which may indicate that cortical arousal during the night is (at least in part) elicited by pre-sleep worry and rumination.

Rapid eye movement sleep parasympathetic activity predicts wake hyperarousal symptoms following a traumatic event.

Heart rate variability (HRV) can be used to assess changes in output of the parasympathetic nervous system (PNS). Considering that patients with post-traumatic stress disorder (PTSD) often experience disturbances in sleep, arousal, and autonomic functioning, we sought to explore the association of PNS activity during sleep with hyperarousal symptoms of PTSD. Because a broad literature supports the importance of rapid eye movement (REM) sleep in PTSD, REM-sleep features were specifically examined as predictors of PTSD symptom severity. A total of 90 participants, primarily civilian and female, aged 18-40 years who had experienced a traumatic event in the last 2 years, underwent an ambulatory polysomnography (PSG) acclimation night followed by a second PSG night from which sleep physiological measures were computed. Participants underwent an ambulatory polysomnography (PSG) acclimation night followed by a second PSG night from which sleep physiological measures were computed. PTSD severity was measured using the PTSD Checklist for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (PCL-5). Dependent variables were total PCL-5 score as well as its hyperarousal symptom subscore. Predictors included REM latency, percentage, density, segment length, and an index of parasympathetic tone (root mean square of the successive differences in the R-R interval or RMSSD). Hierarchical regression models were conducted to analyse the association of REM features with PCL-5 total and hyperarousal subscales. Using hierarchical regression, REM-sleep RMSSD accounted for a significant proportion of the variation in outcome variables, even when accounting for other REM-sleep features. The present findings support hypothesised relationships between PTSD symptomatology and REM-sleep physiology and, specifically, that lowered parasympathetic tone in REM may be an important associate of the hyperarousal symptom cluster in PTSD.

Functional connectivity correlates of attentional networks in insomnia disorder: A pilot study.

Insomnia disorder has been associated with poor executive functioning. Functional imaging studies of executive functioning in insomnia are scarce and inconclusive. Because the Attentional Network Test relies on well-defined cortical networks and sensitively distinguishes different aspects of executive function, it might reveal brain functional alterations in relatively small samples of patients. The current pilot study assessed functional connectivity during the Attentional Network Test performed using magnetic resonance imaging in 12 participants with insomnia and 13 self-defined good sleepers. ANCOVAs were used to evaluate group differences in performance and functional connectivity in the regions of interest representing the attentional networks (i.e. alerting, orienting and executive control) at p < 0.05, uncorrected. During the orienting part, participants with insomnia showed weaker connectivity of the precentral gyrus with the superior parietal lobe (false discovery rate-corrected), while they showed stronger connectivity between premotor and visual regions. Individual differences in connectivity between premotor and visual regions correlated inversely with reaction time. Reaction times suggested more efficient executive control in participants with insomnia compared with good sleepers. During the executive control part, participants with insomnia showed stronger connectivity of thalamic parts of the arousal circuit with the middle frontal and the occipital gyri. Conversely, connectivity between the inferior and superior frontal gyri was weaker. Participants with insomnia seem to recruit more cortical resources in visuo-motor regions to orient attention than good sleepers do, and seem to have enhanced executive control that relates to stronger connectivity of arousal-related thalamic areas. This latter result should be treated with caution and requires confirmation.

Abnormal alterations of regional spontaneous neuronal activity and functional connectivity in insomnia patients with difficulty falling asleep: a resting-state fMRI study.

BACKGROUND: Insomnia disorder (ID) seriously affects people's daily life. Difficulty falling asleep is the most commonly reported complaint in patients with ID. However, the mechanism of prolonged sleep latency (SL) is still obscure. The aim of our present study was to investigate the relationship between prolonged SL and alterations in spontaneous neural activity and brain functional connectivity (FC) in ID patients using functional magnetic resonance imaging (fMRI). METHODS: A total of 52 insomniacs with difficulty falling asleep and 30 matched healthy controls (HCs) underwent resting-state fMRI. The amplitude of low-frequency fluctuation (ALFF) was measured and group differences were compared. The peak areas with significantly different ALFF values were identified as the seed regions to calculate FC to the whole brain. SL was assessed by a wrist actigraphy device in ID patients. The Pittsburgh Sleep Quality Index (PSQI), Hamilton Anxiety Rating Scale (HAMA), and Hyperarousal Scale (HAS) were evaluated in both ID patients and HCs. Finally, correlation analyses were performed between the clinical features and FC/ALFF values. RESULTS: ID patients showed higher PSQI, HAMA, HAS scores than HCs. The functional MRI results indicated increased ALFF value in the left insula and right amygdala and decreased ALFF value in the right superior parietal lobe (SPL) in ID patients. The seed-based FC analysis demonstrated increased FC between the left insula and the bilateral precentral gyrus and FC between the right amygdala and the left posterior cingulate cortex (PCC) in patients with ID. Correlation analysis indicated that the increased FC value of the right amygdala-left PCC was positively correlated with SL measured by actigraphy. CONCLUSION: This study revealed abnormal regional spontaneous fluctuations in the right amygdala, left insula, and right SPL, as well as increased FC in the left insula-precentral and right amygdala-left PCC. Moreover, the prolonged SL was positively correlated with the abnormal FC in the right amygdala-left PCC in ID patients. The current study showed the correlation between prolonged SL and the abnormal function of emotion-related brain regions in ID patients, which may contribute to a better understanding of the neural mechanisms underlying difficulty falling asleep in patients with ID. CLINICAL TRIAL REGISTRATION: http://www.chictr.org.cn ., ChiCTR1800015282. Registered on 20th March 2018.

The Role of Hyperarousal and Aberrant Salience in the Acceptance of Anti-COVID-19 Vaccination.

Background and Objectives: This present study was aimed at exploring hyperarousal and aberrant salience in a sample of the Italian general population to understand their possible role in the acceptance of anti-COVID-19 vaccination. Materials and Methods: Sociodemographic data questions, the "Acceptance of Vaccination" measure, the Hyperarousal Scale (H-Scale), and the Aberrant Salience Inventory (ASI) were sent as an unpaid online survey to the general population (age range 18-80 years) within the Italian territory. Results: The enrolled subjects were divided into two subgroups: "Pro-vax" (n = 806; 87.4%) and "No-vax" (n = 116; 12.6%). Statistical analysis showed significant differences between groups in the "Education Level" (p = 0.001) category, higher in the "Pro-vax" group, and in the ASI "Senses Sharpening" (p = 0.007), "Heightened Emotionality" (p = 0.008), and "Heightened Cognition" (p = 0.002) subscales with the "Total Score" (p = 0.015), all higher in "No-vax" subjects. Furthermore, a linear regression model evidenced that only "Education Level" (ß = 0.143; p < 0.0001) and "Senses Sharpening" (ß = -0.150; p = 0.006) were, respectively, direct and inverse predictors of "Acceptance of Vaccination". Conclusions: Our results show that several subthreshold conditions, such as somatosensory amplification, anxiety traits, and panic experiences, should be taken into account by authoritative sources involved in health education, communication, and policy to alleviate public concerns about vaccine safety, for the present and also future pandemics, and to provide more inclusive, informed, and accurate public health preventive and treatment programs.

Consequences of child maltreatment: A glimpse at stress and sleep.

The present study goal was to provide further information on the association of maltreatment experiences in childhood (CM) and impaired sleep taking the hyperarousal theory of insomnia and stress reaction into account. In all, 62 participants took part in the study. CM history (Childhood Trauma Questionnaire) and subjective sleep quality (Pittsburgh Sleep Quality Index) were assessed before study commencement. In addition, participants wore an actigraph for 6-7 consecutive nights and completed a sleep log during this time. After 3-4 days, the participants took part in a laboratory stress paradigm (Maastricht Acute Stress Test) with 29 participants in the experimental and 31 in the control condition. Saliva cortisol samples were taken before and after the experiment and heart rate variability was assessed. CM was positively correlated with impaired subjectively assessed sleep in adulthood. The stress manipulation led to heightened subjective and physiological stress. Although lower cortisol changes after and lower mean heart rate values during the stress induction were found in the CM group, the differences were not statistically significant. There was no observable sleep reactivity on the stress induction. Stress and CM appear to have long-term effects on subjective sleep. Acute social stress does not directly worsen sleep quality, neither in participants with nor without a history of CM. However, the association underlines the importance of prevention and intervention. When treating sleep impairments, potential CM experiences should be taken into account.

Effects of alcohol on sleep and nocturnal heart rate: Relationships to intoxication and morning-after effects.

BACKGROUND: Alcohol consumption produces feelings of well-being and stimulation, but also impairs psychomotor performance, disturbs cardiovascular function and sleep, and can disrupt next-day mood and behavior. A deeper understanding of how the acute effects of alcohol relate to its sleep and morning-after effects is needed to minimize harm resulting from its use. This study examined relationships between the effects of a high dose of alcohol on subjective and psychomotor measures, nocturnal heart rate, sleep quality, and morning-after mood and behavior. We hypothesized that alcohol would produce disturbances in cardiovascular and sleep regulation during the night, which would predict morning-after mood and behavioral performance. METHODS: Thirty-one men and women participated in two overnight laboratory visits during which they consumed either alcohol (1.0 g/kg for men, 0.85 g/kg for women) or placebo (randomized, crossover design). They consumed the beverage from 8 to 9 pm, and remained in the laboratory overnight for polysomnographic sleep recording. Subjective and behavioral measures were obtained during consumption and at 7-8 am the morning after. RESULTS: Alcohol increased both negative and positive arousal, urge to drink and sedation, and it impaired performance on behavioral tasks. During sleep, alcohol produced expected tachycardia and detriments in sleep quality including decreased total sleep time, sleep efficiency, and altered sleep architecture. Only modest effects on mood or performance were detected the following morning. The acute sedative-like effects of alcohol were related to increases in N2 sleep, but not to other disruptions in sleep or nocturnal heart rate, and neither sleep impairments nor nocturnal heart rate were related to mood or task performance the morning after. CONCLUSIONS: The effects of alcohol on sleep and nocturnal heart rate were not strongly related to either its acute or morning-after effects. These findings do not provide strong support for the idea that alcohol-induced sleep disruptions underlie morning-after effects.

Do posttraumatic stress symptoms predict trajectories of sleep disturbance and fatigue in patients with breast cancer? A parallel-process latent growth model.

OBJECTIVE: Using a parallel-process latent growth model (LGM), this study examined whether posttraumatic stress symptoms (PTSS) are associated with the trajectory of sleep disturbance (SD) and fatigue and whether the SD trajectory mediates the PTSS-fatigue relationship. METHODS: Data were from 215 patients with breast cancer recruited from a tertiary hospital in South Korea. A self-report survey was administered at four time points during the course of adjuvant chemotherapy. RESULTS: The mean age of the participants was 46.69 (SD = 9.08) and the majority was at stage I and the average months since diagnosis was 1.33 (SD = 1.43). Unconditional parallel-process LGM indicated that SD and fatigue were positively associated with each other, both in terms of initial status and growth rate. Then, the conditional parallel-process LGM with baseline PTSS (i.e., avoidance, intrusion, and hyperarousal) as predictors were examined and anxiety, depressive symptoms and chronotype were entered as covariates in the model. Results indicated that a higher initial status and faster growth of SD were associated with a faster increase in fatigue. Greater baseline hyperarousal was directly related to a higher initial status and a slower increase in SD, and higher initial fatigue. Furthermore, a higher hyperarousal was associated with a greater initial SD, which was related to a faster increase in fatigue. Additionally, the late chronotype was related to a faster increase in fatigue through its impact on the initial SD. CONCLUSIONS: The detrimental impact of hyperarousal on the SD trajectory and fatigue suggests the need to intervene in PTSS and SD early and throughout the course of cancer treatments to prevent fatigue.

High-fat diet attenuates morphine withdrawal effects on sensory-evoked locus coeruleus norepinephrine neural activity in male obese rats.

Objective: These experiments sought to characterize the effects of obesity propensity and obesogenic diet on locus coeruleus (LC) norepinephrine (NE) activity and determine the effects of obesity on LC neural responses to morphine withdrawal.Methods: In vivo single-unit LC electrophysiological activity was measured in obese prone (OP) and obese resistant (OR) male SD rats following high-fat (HFD: 45% fat) or low-fat (LFD; 10% fat) feeding. A separate cohort of LFD and HFD rats underwent in vivo LC recording on day 3 of spontaneous morphine withdrawal following an escalation dose paradigm (5-15 mg/kg; SQ twice daily).Results: OP (LFD: 34 cells/7 rats; HFD: 32 cells/6 rats) had higher spontaneous and tonic activity, and lower sensory-evoked activity compared with OR (LFD: 31 cells/6 rats; HFD: 41 cells/7 rats). Interacting effect of diet x strain status was observed on signal-to-noise ratio with OR-LFD having higher ratio than OP-LFD and OP-HFD. Morphine treatment decreased body weights. Withdrawal increased sensory-evoked rate in LFD (morphine; 20 cells/10 rats; saline 24 cells/6 rats) but not HFD (saline: 22 cells/7 rats; morphine: 21 cells/5 rats) rats. In a separate group of age-matched SD rats, a similar weight loss (5-7%) in response to the morphine did not alter sensory-evoked rate but decreased signal-to-noise ratio (Control: 22 cells/8 rats; Weight-matched: 23 cells/8 rats).Discussion: Taken together, our findings suggest that obesity and diet alter the sensory-evoked LC-NE neural responses, which could have implication for emotional stress and opioid-withdrawal behaviors.

Development and validation of the Japanese version of the Hyperarousal Scale.

BACKGROUND: The objectives of this study were to develop a Japanese version of the Hyperarousal Scale (HAS-J) and investigate its factor structure, reliability, and validity, as well as to calculate a cutoff score for the HAS-J and assess different levels of hyperarousal in insomnia patients and community dwellers. METHODS: We recruited 224 outpatients receiving insomnia treatment (56.3% women; mean age 51.7 ± 15.6 years) and 303 community dwellers aged 20 years or older (57.8% women; mean age 43.9 ± 15.2 years). Exploratory and confirmatory factor analysis was performed to examine the factor structure of the HAS-J. Cronbach's α and McDonald's ω were then used to test internal consistency. To examine the scale's validity, we determined correlations between the HAS-J and other indexes and compared HAS-J scores between insomnia patients and community dwellers. We also compared HAS-J scores between two community-dweller groups (normal and poor sleepers) and two insomnia patient groups (with and without alleviation after treatment). RESULTS: Following exploratory and confirmatory factor analysis, a 20-item measure emerged comprising three factors: "Introspectiveness and Reactivity," "Neuroticism," and "Insomnia." Confirmatory factor analysis showed a generally good fit for the model of the three-factor structure suggested by the exploratory factor analysis loadings (χ2 (163) = 327.423, (p <  0.001), CFI = 0.914, GFI = 0.872, AGFI = 0.835, RMSEA = 0.067). In insomnia patients, internal consistency indicated sufficient reliability of the HAS-J. Correlation analysis showed weak to moderate positive correlations of the HAS-J score with other indexes, indicating concurrent validity of the HAS-J. All HAS-J subscale scores were significantly higher in insomnia patients than in community dwellers. Additionally, the total score in patients with alleviation of insomnia was comparable to that in poor sleepers and significantly higher than that in normal sleepers. CONCLUSIONS: This study demonstrated the reliability and validity of the HAS-J, indicating that it is useful as a clinical scale of hyperarousal. The high level of hyperarousal in insomnia patients who were assessed to be in remission by the Insomnia Severity Index suggests a risk of insomnia recurrence in these patients.

A Randomized Controlled Trial Comparing Neurofeedback and Cognitive-Behavioral Therapy for Insomnia Patients: Pilot Study.

Insomnia is a common disease that negatively affects patients both mentally and physically. While insomnia disorder is mainly characterized by hyperarousal, a few studies that have directly intervened with cortical arousal. This study was conducted to investigate the effect of a neurofeedback protocol for reducing cortical arousal on insomnia compared to cognitive-behavioral treatment for insomnia (CBT-I). Seventeen adults with insomnia, free of other psychiatric illnesses, were randomly assigned to neurofeedback or CBT-I. All participants completed questionnaires on insomnia [Insomnia Severity Index (ISI)], sleep quality [Pittsburgh Sleep Quality Index (PSQI)], and dysfunctional cognition [Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS-16)]. The neurofeedback group showed decreases in beta waves and increases in theta and alpha waves in various areas of the electroencephalogram (EEG), indicating lowered cortical arousal. The ISI and PSQI scores were significantly decreased, and sleep efficiency and sleep satisfaction were increased compared to the pre-treatment scores in both groups. DBAS scores decreased only in the CBT-I group (NF p = 0.173; CBT-I p = 0.012). This study confirmed that neurofeedback training could alleviate the symptoms of insomnia by reducing cortical hyperarousal in patients, despite the limited effect in reducing cognitive dysfunction compared to CBT-I.