The role of objective sleep in implicit and explicit affect regulation: A comprehensive review.

Impairments in sleep and affect regulation are evident across a wide range of mental disorders. Understanding the sleep factors that relate to affect regulatory difficulties will inform mechanistic understanding and aid in treatment. Despite rising interest, some research challenges in this area include integrating across different clinical and non-clinical literatures investigating the role of sleep architecture (measured with polysomnography) and experimentally manipulated sleep, as well as integrating more explicit versus implicit affect regulation processes. In this comprehensive review, we use a unifying framework to examine sleep's relationship with implicit-automatic regulation and explicit-controlled regulation, both of which are relevant to mental health (e.g., PTSD and depression). Many studies of implicit-automatic regulation (e.g., fear extinction and safety learning) demonstrate the importance of sleep, and REM sleep specifically. Studies of explicit-controlled regulation (e.g., cognitive reappraisal and expressive suppression) are less consistent in their findings, with results differing depending on the type of affect regulation and/or way that sleep was measured or manipulated. There is a clear relationship between objective sleep and affect regulation processes. However, there is a need for 1) more studies focusing on sleep and explicit-controlled affect regulation; 2) replication with the same types of regulation strategies; 3) more studies experimentally manipulating sleep to examine its impact on affect regulation and vice versa in order to infer cause and effect; and 4) more studies looking at sleep's impact on next-day affect regulation (not just overnight change in affect reactivity).

Beta spectral power during sleep is associated with impaired recall of extinguished fear.

The failure to retain memory for extinguished fear plays a major role in the maintenance of posttraumatic stress disorder (PTSD), with successful extinction recall necessary for symptom reduction. Disturbed sleep, a hallmark symptom of PTSD, impairs fear extinction recall. However, our understanding of the electrophysiological mechanisms underpinning sleep's role in extinction retention remains underdetermined. We examined the relationship between the microarchitecture of sleep and extinction recall in healthy humans (n = 71, both male and females included) and a pilot study in individuals with PTSD (n = 12). Participants underwent a fear conditioning and extinction protocol over 2 days, with sleep recording occurring between conditioning and extinction. Twenty-four hours after extinction learning, participants underwent extinction recall. Power spectral density (PSD) was computed for pre- and post-extinction learning sleep. Increased beta-band PSD (~17-26 Hz) during pre-extinction learning sleep was associated with worse extinction recall in healthy participants (r = 0.41, p = .004). Beta PSD was highly stable across three nights of sleep (intraclass correlation coefficients > 0.92). Results suggest beta-band PSD is specifically implicated in difficulties recalling extinguished fear.

The Impact of Sleep on Fear Extinction.

Sleep plays a crucial role in the consolidation of memories, including those for fear acquisition and extinction training. This chapter reviews findings from studies testing this relationship in laboratory, naturalistic, and clinical settings. While evidence is mixed, several studies in humans have linked fear and extinction recall/retention to both rapid eye-movement and slow wave sleep. Sleep appears to further aid in the processing of both simulated and actual trauma and improves psychotherapeutic treatment outcomes in those with anxiety and trauma- and stressor-related disorders. This chapter concludes with a discussion of the current challenges facing sleep and emotional memory research in addition to suggestions for improving future research.

Utility of Wrist-Wearable Data for Assessing Pain, Sleep, and Anxiety Outcomes After Traumatic Stress Exposure.

Importance: Adverse posttraumatic neuropsychiatric sequelae after traumatic stress exposure are common and have higher incidence among socioeconomically disadvantaged populations. Pain, depression, avoidance of trauma reminders, reexperiencing trauma, anxiety, hyperarousal, sleep disruption, and nightmares have been reported. Wrist-wearable devices with accelerometers capable of assessing 24-hour rest-activity characteristics are prevalent and may have utility in measuring these outcomes. Objective: To evaluate whether wrist-wearable devices can provide useful biomarkers for recovery after traumatic stress exposure. Design, Setting, and Participants: Data were analyzed from a diverse cohort of individuals seen in the emergency department after experiencing a traumatic stress exposure, as part of the Advancing Understanding of Recovery After Trauma (AURORA) study. Participants recruited from 27 emergency departments wore wrist-wearable devices for 8 weeks, beginning in the emergency department, and completed serial assessments of neuropsychiatric symptoms. A total of 19 019 patients were screened. Of these, 3040 patients met study criteria, provided informed consent, and completed baseline assessments. A total of 2021 provided data from wrist-wearable devices, completed the 8-week assessment, and were included in this analysis. The data were randomly divided into 2 equal parts (n = 1010) for biomarker identification and validation. Data were collected from September 2017 to January 2020, and data were analyzed from May 2020 to November 2022. Exposures: Participants were recruited for the study after experiencing a traumatic stress exposure (most commonly motor vehicle collision). Main Outcomes and Measures: Rest-activity characteristics were derived and validated from wrist-wearable devices associated with specific self-reported symptom domains at a point in time and changes in symptom severity over time. Results: Of 2021 included patients, 1257 (62.2%) were female, and the mean (SD) age was 35.8 (13.0) years. Eight wrist-wearable device biomarkers for symptoms of adverse posttraumatic neuropsychiatric sequelae exceeded significance thresholds in the derivation cohort. One of these, reduced 24-hour activity variance, was associated with greater pain severity (r = -0.14; 95% CI, -0.20 to -0.07). Changes in 6 rest-activity measures were associated with changes in pain over time, and changes in the number of transitions between sleep and wake over time were associated with changes in pain, sleep, and anxiety. Simple cutoffs for these biomarkers identified individuals with good recovery for pain (positive predictive value [PPV], 0.85; 95% CI, 0.82-0.88), sleep (PPV, 0.63; 95% CI, 0.59-0.67, and anxiety (PPV, 0.76; 95% CI, 0.72-0.80) with high predictive value. Conclusions and Relevance: These findings suggest that wrist-wearable device biomarkers may have utility as screening tools for pain, sleep, and anxiety symptom outcomes after trauma exposure in high-risk populations.

Worse sleep, worsening post-traumatic stress disorder (PTSD): Poor sleep quality associated with increases in PTSD symptoms amongst those experiencing high threat of the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic is a global health crisis with the potential to elicit and worsen psychiatric symptoms, particularly post-traumatic stress disorder (PTSD) symptoms. Identifying modifiable protective factors is critical for preventing and treating PTSD symptoms both during and following the COVID-19 pandemic. The present study examined associations of self-reported sleep quality and anticipatory threat appraisals of the pandemic with PTSD symptoms 6 months later in a sample enriched for pre-pandemic trauma exposure and PTSD. The sample included 590 adults (mean age 38.2 years) who completed a baseline survey in August/September 2020 and follow-up survey in March/April 2021. The sample was recruited from a pool of participants interested in a prior study about traumatic stress. Participants self-reported sleep quality and pandemic-related anticipatory threat appraisals at baseline. PTSD symptoms were assessed at baseline and follow-up. Baseline sleep quality was associated with PTSD symptoms at follow-up controlling for baseline PTSD symptoms (B = -2.49, p = 0.001). Perceived anticipatory threat of the pandemic moderated this association such that worse sleep quality was related to more severe PTSD symptoms at follow-up for participants with higher (B = -4.07, p < 0.001) but not lower (B = -0.43, p = 0.679) anticipatory threat about the COVID-19 pandemic. These findings suggest that poor sleep quality may enhance vulnerability to later PTSD symptoms during the pandemic, particularly among those individuals who perceived the pandemic as threatening for their future. Treatments that address sleep problems may be beneficial for reducing trauma-related symptoms during and following the global health crisis.

The relationship of fear-potentiated startle and polysomnography-measured sleep in trauma-exposed men and women with and without PTSD: testing REM sleep effects and exploring the roles of an integrative measure of sleep, PTSD symptoms, and biological sex.

STUDY OBJECTIVES: Published research indicates that sleep is involved in emotional information processing. Using a fear-potentiated startle (FPS) and nap sleep protocol, we examined the relationship of emotional learning with REM sleep (REMS) in trauma-exposed participants. We also explored the roles of posttraumatic stress disorder (PTSD) symptoms, biological sex, and an integrative measure of polysomnography-measured (PSG) sleep in the learning-sleep relationship. METHODS: After an adaptation nap, participants (N = 46) completed two more visits (counterbalanced): a stress-condition visit, which included FPS conditioning procedures prior to a nap and assessment of learning retention and fear extinction training after the nap, and a control visit, which included a nap opportunity without stressful procedures. FPS conditioning included a "fear" visual stimulus paired with an air blast to the neck and a "safety" visual stimulus never paired with an air blast. Retention and extinction involved presentation of the visual stimuli without the air blast. Primary analyses examined the relationship between FPS responses pre- and post-sleep with stress-condition REMS duration, controlling for control-nap REMS duration. RESULTS: Higher safety learning predicted increased REMS and increased REMS predicted more rapid extinction learning. Similar relationships were observed with an integrative PSG sleep measure. They also showed unexpected effects of PTSD symptoms on learning and showed biological sex effects on learning-sleep relationships. CONCLUSIONS: Findings support evidence of a relationship between adaptive emotional learning and REMS. They underscore the importance of examining sex effects in sleep-learning relationships. They introduce an integrative PSG sleep measure with potential relevance to studies of sleep and subjective and biological outcomes.

Reducing Barriers to Behavioral Treatments for Insomnia: A Qualitative Examination of Veterans' Perspectives of BBTI.

Objective: Although behavioral treatments are recommended for treating insomnia disorder, these treatments are not the most commonly provided treatments due to numerous barriers (e.g., treatment length, time limitations). Brief Behavioral Treatment for Insomnia (BBTI) was developed, in part, to help overcome these barriers. The purpose of the current study was to qualitatively examine the treatment experiences of veterans with insomnia disorder participating in BBTI.Methods: All veterans (n=46) who were randomized to receive BBTI as part of a randomized clinical trial participated in 10-20 minute semi-structured interviews one week after completing treatment. Rapid analysis procedures were used for qualitative analysis.Results: Thirteen qualitative themes were identified: BBTI provided veterans with the skills they believed they needed to continue improving independently post-treatment; beginning BBTI with in-person sessions was valued; phone sessions helped participation; veterans did not perceive that they could cover the same content during phone and in-person sessionsl; materials could be more portable; BBTI created accountability; BBTI required discipline and willingness; BBTI facilitated buy-in; BBTI was aligned with military culture; loved ones could provide important support; BBTI could be improved with more personalization; BBTI challenged expectations of mental health; and BBTI improved awareness of health behaviors beyond sleep.Conclusions: BBTI was successful in overcoming barriers to behavioral insomnia treatment and interviews identified critical treatment aspects that should be maintained to preserve acceptability (e.g., in-person session first). Areas in which BBTI did not fully meet the needs of veterans and targets for improvement (e.g., ameliorating understanding and expectations of phone sessions) were also identified.

Diagnosing obstructive sleep apnea in a residential treatment program for veterans with substance use disorder and PTSD.

BACKGROUND: Obstructive sleep apnea (OSA) is often comorbid with both substance use disorders (SUD) and posttraumatic stress disorder (PTSD), yet frequently goes undiagnosed and untreated. We present data on the feasibility and acceptability of objective OSA diagnosis procedures, findings on OSA prevalence, and the relationship between OSA and baseline SUD/PTSD symptoms among veterans in residential treatment for comorbid PTSD/SUD. METHODS: Participants were 47 veterans admitted to residential PTSD/SUD treatment. Participants completed questionnaires assessing PTSD and sleep symptoms, and filled out a sleep diary for seven days. Apnea-hypopnea index (AHI) was recorded using the overnight Home Sleep Apnea test (HSAT; OSA was diagnosed with AHI ≥ 5). RESULTS: Objective OSA diagnostic testing was successfully completed in 95.7% of participants. Of the 45 veterans who went through HSAT, 46.7% had no OSA, 35.6% received a new OSA diagnosis, and 8.9% were previously diagnosed with OSA and were using positive airway pressure treatment (PAP); an additional 8.9% were previously diagnosed with OSA, reconfirmed with the HSAT, but were not using PAP. One hundred percent of respondents during follow-up deemed the testing protocol's usefulness as "Good" or "Excellent." CONCLUSION: OSA diagnostic testing on the residential unit was feasible and acceptable by participants and was effective in diagnosing OSA. OSA testing should be considered for everyone entering a SUD and PTSD residential unit. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Cognitive behavioral therapy for insomnia in veterans with gulf war illness: Results from a randomized controlled trial.

AIMS: To examine whether cognitive behavioral therapy for insomnia (CBT-I), delivered by telephone, improves sleep and non-sleep symptoms of Gulf War Illness (GWI). MAIN METHODS: Eighty-five Gulf War veterans (21 women, mean age: 54 years, range 46-72 years) who met the Kansas GWI case definition, the Centers for Disease Control and Prevention (CDC) case definition for Chronic Multisymptom Illness (CMI), and research diagnostic criteria for insomnia disorder were randomly assigned to CBT-I or monitor-only wait list control. Eight weekly sessions of individual CBT-I were administered via telephone by Ph.D. level psychologists to study participants. Outcome measures included pre-, mid-, and post-treatment assessments of GWI and insomnia symptoms, subjective sleep quality, and continuous sleep monitoring with diary. Outcomes were re-assessed 6-months post-treatment in participants randomized to CBT-I. KEY FINDINGS: Compared to wait list, CBT-I produced significant improvements in overall GWI symptom severity, individual measures of fatigue, cognitive dysfunction, depression and anxiety, insomnia severity, subjective sleep quality, and sleep diary outcome measures. The beneficial effects of CBT-I on overall GWI symptom severity and most individual GWI symptom measures were maintained 6-months after treatment. SIGNIFICANCE: GWI symptoms have historically been difficult to treat. Because CBT-I, which is associated with low stigma and is increasingly readily available to veterans, improved both sleep and non-sleep symptoms of GWI, these results suggest that a comprehensive approach to the treatment of GWI should include behavioral sleep interventions.

Diurnal Rhythm Robustness in Individuals With PTSD and Insomnia and The Association With Sleep.

Posttraumatic stress disorder (PTSD) and insomnia are characterized by sleep disturbances and daytime functional impairments. Actigraphy metrics can quantify diurnal rhythms via interdaily stability, intradaily variability, relative amplitude, and sleep regularity. Here, we (a) compared diurnal rhythms in PTSD, insomnia, and healthy control samples using linear mixed modeling; (b) compared inter-individual variability of diurnal rhythms between groups using variance ratio tests; and (c) examined correlations between diurnal rhythms and sleep measures within the clinical samples. Participants (N = 98) wore wrist-activity monitors for one week and completed the Insomnia Severity Index and Pittsburgh Sleep Quality Index. Both clinical samples displayed significantly lower interdaily stability, relative amplitude, and sleep regularity compared with controls. Individuals with PTSD and insomnia did not differ on mean diurnal rhythm metrics. Both clinical samples showed more inter-individual variability in relative amplitude compared with controls, and the individuals with PTSD were distinguished from those with insomnia by greater inter-individual variability in interdaily stability and relative amplitude. Relative amplitude in the clinical samples was positively correlated with objective sleep efficiency and total sleep time. This is the first study to compare individuals with PTSD and insomnia on measures of diurnal rhythms, revealing those with PTSD and insomnia to have less robust and more variable diurnal rhythms compared with controls. Individuals with PTSD differed from those with insomnia in inter-individual variability of diurnal rest-activity stability and amplitude, highlighting this population as particularly heterogenous. Diurnal rhythm robustness might be considered an intervention target in insomnia and PTSD populations.

Brief behavioral treatment for insomnia improves psychosocial functioning in veterans: results from a randomized controlled trial.

STUDY OBJECTIVES: Our goal was to compare brief behavioral treatment for insomnia (BBTI) to a progressive muscle relaxation training (PMRT) control condition among veterans with insomnia, examining psychosocial functioning as a primary outcome and sleep-related outcomes, mood, cognition, and pain as secondary outcomes. METHODS: Veterans were randomly assigned to either BBTI or PMRT (N = 91; 24-74 years; M = 49 years). BBTI consisted of two in-person (60-min and 30-min sessions) and two telephone sessions (20-min each), and the PMRT control condition was matched to BBTI for session duration and type. Veterans were assessed through clinical interview at baseline and self-report measures at pre-, mid-, and posttreatment, as well as 6-month follow-up for the BBTI condition to assess sustained response. Measures also included continuous sleep monitoring with sleep diary. RESULTS: Intent-to-treat analyses demonstrated that individuals who completed BBTI versus PMRT reported greater improvements in work, home, social and cognitive functioning, insomnia symptom severity, mood, and energy. Improvements in psychosocial functioning, insomnia symptoms, and mood were maintained 6-months following BBTI treatment completion. CONCLUSIONS: Veterans who received BBTI improved and maintained gains in psychosocial functioning, insomnia, and mood. BBTI is a treatment that can be implemented in primary care, mental health, or integrated care settings and provide symptom relief and improved functioning among those with insomnia, one of the most commonly reported mental health problems among veterans. CLINICAL TRIAL REGISTRATION: NCT02571452.

Examining sleep over time in a randomized control trial comparing two integrated PTSD and alcohol use disorder treatments.

STUDY OBJECTIVES: Insomnia is highly co-occurring with both posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD). This is concerning since insomnia contributes to worse substance abuse and PTSD, and a host of negative health consequences. No study has tracked how sleep indices and insomnia change related to integrated PTSD and AUD treatment using evidence-based exposure therapy. This study examined how insomnia changes over time in a randomized control trial of two integrated PTSD and AUD treatments. METHODS: Participants were 119 adult veterans (90 % male) seeking treatment for AUD and PTSD at a large urban VA. Participants were randomized to either COPE (integrated treatment using prolonged exposure) or Seeking Safety (integrated therapy using cognitive behavioral, interpersonal techniques and case management). Assessments were done at pre- and post-treatment and include: Clinician Administered PTSD Scale, Timeline Follow-back calendar-assisted interview for AU, insomnia severity index (ISI), sleep diary and actigraphy for 7 days. RESULTS: ISI showed significant decreases, but a majority remained above the clinical cutoff at post-treatment. Wake after sleep onset decreased, but only by 8 min, remaining above clinical thresholds. Decreases in PTSD, but not in heavy drinking, predicted change in ISI. No significant changes were observed in other sleep variables measured. CONCLUSIONS: Findings suggested some statistical improvements in sleep quality, but sleep indices remained above clinical cut-offs. This study provides evidence that insomnia is an independent disorder and not responsive to PTSD or AUD treatments alone. Sleep symptoms should be assessed and treated in patients with comorbid mental health conditions.

Validation of sleep measurement in a multisensor consumer grade wearable device in healthy young adults.

STUDY OBJECTIVES: Our objective was to examine the ability of a consumer-grade wearable device (Basis B1) with accelerometer and heart rate technology to assess sleep patterns compared with polysomnography (PSG) and research-grade actigraphy in healthy adults. METHODS: Eighteen adults underwent consecutive nights of sleep monitoring using Basis B1, actigraphy, and PSG; 40 nights were used in analyses. Discrepancies in gross sleep parameters and epoch-by-epoch agreements in sleep/wake classification were assessed. RESULTS: Basis B1 accuracy was 54.20 ± 8.20%, sensitivity was 98.90 ± 2.70%, and specificity was 8.10 ± 15.00%. Accuracy, sensitivity, and specificity for distinguishing between the different sleep stages were 60-72%, 48-62%, and 57-86%, respectively. Pearson correlations demonstrated strong associations between Basis B1 and PSG estimates of sleep onset latency and total sleep time; moderate associations for sleep efficiency, duration of light sleep, and duration of rapid eye movement sleep; and a weak association for duration of deep sleep. Basis B1 significantly overestimates total sleep time, sleep efficiency, and duration of light sleep and significantly underestimates wake after sleep onset and duration of deep sleep. CONCLUSIONS: Basis B1 demonstrated utility for estimates of gross sleep parameters and performed similarly to actigraphy for estimates of total sleep time. Basis B1 specificity was poor, and Basis B1 is not useful for the assessment of wake. Basis B1 accuracy for sleep stages was better than chance but is not a suitable replacement for PSG assessment. Despite low cost, ease of use, and attractiveness for patients, consumer devices are not yet accurate or reliable enough to guide treatment decision making in clinical settings.

Work by day and sleep by night, do not sleep too little or too much: Effects of sleep duration, time of day and circadian synchrony on flanker-task performance in internet brain-game users from teens to advanced age.

Research elucidating the effects of sleep and circadian rhythm on cognitive performance is advancing, yet many important questions remain. Using flanker-task performance scores from a large internet sample (N = 48,881) with repeated measures of cognitive performance and linked prior-night self-reported sleep duration, we analysed the relationship between sleep duration, time of day of task performance, and chronotype synchrony with performance in participants aged 15-80 years. Results indicate a performance peak at 7 hr habitual sleep duration, and point to a variable effect of deviation from habitual sleep duration depending on users' habitual sleep duration and age. Time-of-day effects were notable for a steady decline in performance up until 01:00 hours-02:00 hours for the group as a whole, which was accounted for by nighttime deterioration on trials requiring inhibitory executive functioning, particularly in older subjects. Analyses did not demonstrate an advantage for playing in synchrony with self-identified chronotype. Results strengthen findings indicating an inverted U-shaped relationship between sleep duration and cognitive performance across a broad spectrum of age groups. These findings underscore the importance of daytime task performance for tasks requiring inhibitory function, especially in elderly people. Findings highlight the utility of large-scale internet data in contributing to sleep and circadian science.

A Review of the Relationship Between Emotional Learning and Memory, Sleep, and PTSD.

PURPOSE OF REVIEW: The emotional memory and learning model of PTSD posits maladaptive fear conditioning, extinction learning, extinction recall, and safety learning as central mechanisms to PTSD. There is increasingly convincing support that sleep disturbance plays a mechanistic role in these processes. The current review consolidates the evidence on the relationships between emotional memory and learning, disturbed sleep, and PTSD acquisition, maintenance, and treatment. RECENT FINDINGS: While disrupted sleep prior to trauma predicts PTSD onset, maladaptive fear acquisition does not seem to be the mechanism through which PTSD is acquired. Rather, poor extinction learning/recall and safety learning seem to better account for who maintains acute stress responses from trauma versus who naturally recovers; there is convincing evidence that this process is, at least in part, mediated by REM fragmentation. Individuals with PTSD had higher "fear load" during extinction, worse extinction learning, poorer extinction recall, and worse safety learning. Evidence suggests that these processes are also mediated by fragmented REM. Finally, PTSD treatments that require extinction and safety learning may also be affected by REM fragmentation. Addressing fragmented sleep or sleep architecture could be used to increase emotional memory and learning processes and thus ameliorate responses to trauma exposure, reduce PTSD severity, and improve treatment. Future studies should examine relationships between emotional memory and learning and disturbed sleep in clinical PTSD patients.

Altered overnight levels of pro-inflammatory cytokines in men and women with posttraumatic stress disorder.

BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with disturbed sleep and elevated levels of pro-inflammatory cytokines, including interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Studies in animals and healthy humans have also shown that disrupted sleep elevates pro-inflammatory cytokines, including IL-6 and TNF-α. A better understanding of overnight cytokine levels and sleep might shed light on possible mechanisms for elevated inflammation in PTSD. Thus, we investigated overnight levels of IL-6 and TNF-α in individuals with and without PTSD while recording sleep polysomnography (PSG). METHOD: Serum samples were collected from otherwise healthy, medication-free participants with chronic PTSD (n = 44; 50% female; M age = 30.34 ± 8.11) and matched controls (n = 49; 53% female; M age = 30.53 ± 6.57) during laboratory PSG. Levels of IL-6 and TNF-α were measured at hours 0, 2, 4, 6, and 8 after typical sleep onset time using serial serum samples. Plasma IL-6 and TNF-α levels were quantified using enzyme-linked immunosorbent assays. RESULTS: Growth model analysis indicated a significantgroup by time interaction for IL-6 (t[247] = -2.92, p = .005) and a significant group by sex by time interaction for TNF-α (t[275] = 2.02, p = .04). PTSD positive men and women initially had higher IL-6 and TNF-α at sleep onset, but not at the end of their sleep cycle. Men with PTSD showed a peak of TNF-α at the end of the sleep cycle, whereas male control subjects demonstrated an inverted U-shaped profile. There were no significant differences in TNF-α levels overnight between women with and without PTSD. CONCLUSION: To our knowledge, this is the largest study to examine IL-6 overnight in a PTSD sample and the first study to examine overnight TNF-α in PTSD. Overnight IL-6 and TNF-α levels may be altered in individuals with PTSD compared to those without PTSD, and TNF-α trajectories also differed by sex. The current findings highlight the need to consider sex, sleep, time of day, and circadian variation when examining inflammation in PTSD. Additional research in broader study samples will be necessary to clarify associations between disrupted sleep, cytokines, and increased risk for disease in PTSD.

REM sleep and safety signal learning in posttraumatic stress disorder: A preliminary study in military veterans.

BACKGROUND: Posttraumatic Stress Disorder (PTSD) is associated with a number of negative physical and mental health consequences. Fear conditioning plays an important mechanistic role in PTSD, and PTSD patients also show deficits in safety signal learning. Sleep, particularly REM sleep, is linked to improved safety learning and extinction processes in animal models and healthy humans. No studies have examined the link between REM sleep and safety signal learning or extinction memory in clinical populations. METHODS: This study examined the relationship between REM sleep, safety signal learning, and extinction processes in veterans with PTSD (n = 13). Patients' overnight sleep was characterized in the laboratory via polysomnography (PSG). The next day, participants underwent a fear conditioning paradigm during which they acquired fear toward a visual cue. This testing session also included a visual cue that became a safety signal (CS-). Following conditioning, the veterans' sleep was monitored overnight again, after which they underwent extinction training. Following a third night of sleep, extinction recall and safety recall were tested. Bivariate correlations examined the relationship between the slope of safety signal learning and subsequent REM sleep, as well as the relationship between REM sleep and subsequent extinction recall and safety recall on the last day of testing. RESULTS: Veterans learned to differentiate the CS+ and the CS- on the first day of testing. Veterans who underwent safety learning more quickly on the first day of testing showed more efficient REM sleep that night (r = .607, p = .028). On the second day of testing, the patients successfully underwent extinction learning. Patients with a higher percentage of REM sleep on the last night of the study showed more safety recall early on the last day of testing (r = .688, p = .009). CONCLUSION: To our knowledge, this was the first study to examine the relationship between objective sleep and fear-potentiated startle performance in veterans with PTSD. Study methods were well tolerated by participants, supporting feasibility of the experimental design. Results indicated REM sleep was associated with both initial safety learning and subsequent safety recall. Taken together with previous studies in healthy controls, these preliminary results provide additional evidence suggesting REM sleep could play a mechanistic role in the maintenance of PTSD and thus identify a modifiable biological process to target in treatment of PTSD. These findings should be replicated in larger samples.

Cognitive Behavioral Therapy for Insomnia Reduces Fear of Sleep in Individuals With Posttraumatic Stress Disorder.

STUDY OBJECTIVES: Our study aims were to examine (1) the association between fear of sleep and posttraumatic stress disorder (PTSD) symptoms, (2) the association between fear of sleep and subjective and objective insomnia symptoms and disruptive behaviors during sleep, and (3) whether fear of sleep decreases following cognitive behavioral therapy for insomnia (CBT-I). METHODS: Forty-five adults with PTSD and insomnia participated in the study. Fear of sleep was assessed using the Fear of Sleep Inventory; PTSD symptoms were assessed using the Clinician Administered PTSD Scale; and sleep disturbance symptoms were assessed using the Insomnia Severity Index, polysomnography, sleep diaries, and the Pittsburgh Sleep Quality Index Addendum for PTSD. Participants were randomly assigned to 8 weeks of CBT-I (n = 29) or a waitlist control condition (n = 16). RESULTS: Greater fear of sleep was associated with greater PTSD symptom severity, greater nightmare frequency, and greater hypervigilance intensity. Greater fear of sleep was associated with decreased wake after sleep onset (WASO), reduced total sleep time, and greater disruptive nocturnal behaviors. Following CBT-I, there was a significant reduction in fear of sleep compared to the waitlist condition. These improvements persisted 6 months later. CONCLUSIONS: Fear of sleep was related to sleep disturbances specific to trauma rather than "classic" insomnia symptoms. Unexpectedly, greater fear of sleep was associated with reduced WASO. These results may be related to having a truncated sleep period and thus more consolidated sleep. Fear of sleep deceased following CBT-I despite not being a permissible target for this research protocol and not being related to insomnia symptoms. CLINICAL TRIAL REGISTRATION: Registry: CinicalTrials.gov; Name: Treating People with Post-traumatic Stress Disorder with Cognitive Behavioral Therapy for Insomnia; Identifier: NCT00881647; URL: https://clinicaltrials.gov/ct2/show/NCT00881647.