Antidepressant effects of acute sleep deprivation are reduced in highly controlled environments.

BACKGROUND: Numerous studies summarized in a recent meta-analysis have shown sleep deprivation rapidly improves depressive symptoms in approximately 50 % of individuals with major depressive disorder (MDD), however those studies were typically conducted in clinical settings. Here we investigated the effects of sleep deprivation utilizing a highly controlled experimental approach. METHODS: 36 antidepressant-free individuals with MDD and 10 healthy controls (HC) completed a 5 day/4-night protocol consisting of adaptation, baseline, total sleep deprivation (TSD), and recovery phases. Light was kept consistently dim (≤50 lx), meals were regulated, and activity was restricted. In-the-moment mood was assessed using a modified Hamilton Rating Scale for Depression (HRSD) at screening and each morning following the experimental nights. RESULTS: Day of study had a significant effect on mood in both groups. Post-hoc analyses revealed that significant effects were attributed to mood improvement in the MDD group following study initiation prior to beginning TSD, and in the HC group following recovery sleep, but were not due to mood improvement in the MDD group during TSD. No further improvement in mood occurred during 36 h of TSD. LIMITATIONS: Strict eligibility requirements may limit generalizability. The requirement to be medication free may have biased toward a less severely depressed sample. CONCLUSIONS: Results revealed that individuals with moderate MDD can experience a significant reduction in depressive symptoms upon entering a highly controlled laboratory environment. Environmental effects on mood can be substantial and need to be considered.

Enhanced amygdala-cingulate connectivity associates with better mood in both healthy and depressive individuals after sleep deprivation.

Sleep loss robustly disrupts mood and emotion regulation in healthy individuals but can have a transient antidepressant effect in a subset of patients with depression. The neural mechanisms underlying this paradoxical effect remain unclear. Previous studies suggest that the amygdala and dorsal nexus (DN) play key roles in depressive mood regulation. Here, we used functional MRI to examine associations between amygdala- and DN-related resting-state connectivity alterations and mood changes after one night of total sleep deprivation (TSD) in both healthy adults and patients with major depressive disorder using strictly controlled in-laboratory studies. Behavioral data showed that TSD increased negative mood in healthy participants but reduced depressive symptoms in 43% of patients. Imaging data showed that TSD enhanced both amygdala- and DN-related connectivity in healthy participants. Moreover, enhanced amygdala connectivity to the anterior cingulate cortex (ACC) after TSD associated with better mood in healthy participants and antidepressant effects in depressed patients. These findings support the key role of the amygdala-cingulate circuit in mood regulation in both healthy and depressed populations and suggest that rapid antidepressant treatment may target the enhancement of amygdala-ACC connectivity.

The association of polysomnographic sleep on posttraumatic stress disorder symptom clusters in trauma-exposed civilians and veterans.

Study Objectives: Self-reported sleep disturbance has been established as a risk factor and predictor for posttraumatic stress disorder (PTSD); however, less is known about the relationship between objective sleep and PTSD symptom clusters, and the specific role of hyperarousal. The present study examined the relationships between sleep continuity and architecture on PTSD symptom clusters. Methods: Participants underwent two in-laboratory sleep studies to assess sleep continuity and architecture. They also completed the Clinician-Administered PTSD-IV scale and the Structured Clinical Interview for the DSM-IV to assess for PTSD diagnosis and other psychiatric disorders. Results: Sleep continuity (i.e. total sleep time, sleep efficiency percent, wake after sleep onset, sleep latency) was significantly related to PTSD Cluster B (reexperiencing) symptom severity (R 2 = .27, p < .001). Sleep architecture, specifically Stage N1 sleep, was significantly associated with PTSD Cluster B (t = 2.98, p = .004), C (Avoidance; t = 3.11, p = .003), and D (Hyperarosual; t = 3.79, p < .001) symptom severity independently of Stages N2, N3, and REM sleep. REM sleep variables (i.e. REM latency, number of REM periods) significantly predicted Cluster D symptoms (R 2 = .17, p = .002). Conclusions: These data provide evidence for a relationship between objective sleep and PTSD clusters, showing that processes active during Stage N1 sleep may contribute to PTSD symptomatology in civilians and veterans. Further, these data suggest that arousal mechanisms active during REM sleep may also contribute to PTSD hyperarousal symptoms.This paper is part of the War, Trauma, and Sleep Across the Lifespan Collection. This collection is sponsored by the Sleep Research Society.

A randomized controlled study of convalescent plasma for individuals hospitalized with COVID-19 pneumonia.

BackgroundAntibody-based strategies for COVID-19 have shown promise in prevention and treatment of early disease. COVID-19 convalescent plasma (CCP) has been widely used but results from randomized trials supporting its benefit in hospitalized patients with pneumonia are limited. Here, we assess the efficacy of CCP in severely ill, hospitalized adults with COVID-19 pneumonia.MethodsWe performed a randomized control trial (PennCCP2), with 80 adults hospitalized with COVID-19 pneumonia, comparing up to 2 units of locally sourced CCP plus standard care versus standard care alone. The primary efficacy endpoint was comparison of a clinical severity score. Key secondary outcomes include 14- and 28-day mortality, 14- and 28-day maximum 8-point WHO ordinal score (WHO8) score, duration of supplemental oxygenation or mechanical ventilation, respiratory SARS-CoV-2 RNA, and anti-SARS-CoV-2 antibodies.ResultsEighty hospitalized adults with confirmed COVID-19 pneumonia were enrolled at median day 6 of symptoms and day 1 of hospitalization; 60% were anti-SARS-CoV-2 antibody seronegative. Participants had a median of 3 comorbidities, including risk factors for severe COVID-19 and immunosuppression. CCP treatment was safe and conferred significant benefit by clinical severity score (median [MED] and interquartile range [IQR] 10 [5.5-30] vs. 7 [2.75-12.25], P = 0.037) and 28-day mortality (n = 10, 26% vs. n = 2, 5%; P = 0.013). All other prespecified outcome measures showed weak evidence toward benefit of CCP.ConclusionTwo units of locally sourced CCP administered early in hospitalization to majority seronegative participants conferred a significant benefit in clinical severity score and 28-day mortality. Results suggest CCP may benefit select populations, especially those with comorbidities who are treated early.Trial RegistrationClinicalTrials.gov NCT04397757.FundingUniversity of Pennsylvania.

Twin-based heritability of actimetry traits.

There is a critical need for phenotypes with substantial heritability that can be used as endophenotypes in behavioral genetic studies. Activity monitoring, called actimetry, has potential as a means of assessing sleep and circadian rhythm traits that could serve as endophenotypes relevant to a range of psychopathologies. This study examined a range of actimetry traits for heritability using a classic twin design. The sample consisted of 195 subjects from 45 monozygotic (MZ) and 50 dizygotic (DZ) twin pairs aged 16-40 years. Subjects wore both a research-grade actimeter (GENEActiv) and a consumer-oriented device (FitBit) for 2 weeks. Sleep and circadian traits were extracted from GENEActiv data using PennZzz and ChronoSapiens software programs. Sleep statistics for a limited number of FitBit-collected traits were generated by its accompanying mobile app. Broad sense heritability was computed on a set of 33 MZ and 38 DZ twin pairs with complete data using both OpenMX and SOLAR software. These analyses yielded a large number of actimetry-derived traits, 20 of which showed high heritability (h2 > 0.6), seven of which remain significant after Bonferroni correction. These results indicate that actimetry enables assessing a range of phenotypes with substantial heritability that may be useful as endophenotypes for genetic studies.

Effects of armodafinil and cognitive behavior therapy for insomnia on sleep continuity and daytime sleepiness in cancer survivors.

STUDY OBJECTIVES: This study involves the analysis of a secondary outcome of a trial examining whether cognitive behavior therapy for insomnia (CBT-I), a wake-promoting medication (armodafinil), or both results in greater improvement in prospectively assessed sleep continuity and daytime sleepiness than a placebo-alone group among a heterogeneous group of cancer survivors. Whether or not armodafinil alone, and/or when combined with CBT-I, affected adherence with CBT-I was evaluated. DESIGN: This study is a randomized, placebo-controlled, clinical trial. SETTING: This study was conducted at two northeastern academic medical centers. PARTICIPANTS: Eighty-eight cancer survivors with chronic insomnia were recruited between October 2008 and November 2012. Participants were assigned to one of four conditions: 1) CBT-I and placebo (CBT-I+P); 2) CBT-I and armodafinil (CBT-I + A); 2) armodafinil alone (ARM); or 4) placebo alone (PLA). INTERVENTIONS: CBT-I was delivered in seven weekly individual therapy sessions (three in person, four via telephone). The armodafinil dosage was 50 mg BID. MEASUREMENTS AND RESULTS: Sleep continuity was measured with daily sleep diaries assessing sleep latency (SL), wake after sleep onset (WASO), and total sleep time (TST). The Epworth Sleepiness Scale (ESS) measured daytime sleepiness. Compared to the PLA group, the CBT-I+P and CBT-I+A groups reported a significant reduction in SL with effect sizes of 0.67 and 0.58, respectively. A significant reduction was observed in WASO in the CBT-I+A group with an effect size of 0.64. An increasing trend of TST was observed in the CBT-I+P, CBT-I+A, and PLA groups, but not in the ARM group. No statistically significant reductions in daytime sleepiness (ESS) were observed for any of the groups. CONCLUSION: CBT-I alone and in combination with armodafinil caused significant improvement in sleep continuity. The addition of armodafinil did not appear to improve daytime sleepiness or enhance adherence to CBT-I.

Stress Reactivity in Insomnia.

This study examined whether individuals with primary insomnia (PI) are more reactive to stress than good sleepers (GS). PI and GS (n = 20 per group), matched on gender and age, completed three nights of polysomnography. On the stress night, participants received a mild electric shock and were told they could receive additional shocks during the night. Saliva samples were obtained for analysis of cortisol and alpha amylase along with self-report and visual analog scales (VAS). There was very little evidence of increased stress on the stress night, compared to the baseline night. There was also no evidence of greater stress reactivity in the PI group for any sleep or for salivary measures. In the GS group, stress reactivity measured by VAS scales was positively associated with an increase in sleep latency in the experimental night on exploratory analyses. Individuals with PI did not show greater stress reactivity compared to GS.

Durability of treatment response to zolpidem with three different maintenance regimens: a preliminary study.

BACKGROUND AND AIM: At present, there is no consensus regarding how to medically manage chronic insomnia in the long term. The unstated standard of practice is for patients to use hypnotics intermittently. The present study aimed to compare a partial reinforcement strategy with nightly and intermittent dosing strategies for its potential as a maintenance therapy. METHODS: A mixed model was used in the study. One between-subjects factor: group (n = 4). One repeated-measures factor: time (12 weekly assessments). A total of 74 subjects with chronic Insomnia were treated with 10 mg zolpidem for 4 weeks. Treatment respondents were randomized to nightly dosing with 10 mg or 5 mg (QHS-10 and QHS-5), intermittent dosing with 10 mg (IDS-10 [3-5 days weekly]), or partial reinforcement dosing with 10 mg (PRS-10 [nightly pill use with 50% active medication and 50% placebos]) for 12 weeks. RESULTS: It was found, in compliant subjects (n = 55), that all four strategies evaluated maintained treatment response over time (ie, prevented or delayed relapse). For the subjects that remained in remission, the subjects in the intermittent dosing group (IDS-10) group exhibited poorer sleep continuity. CONCLUSIONS: While best considered a preliminary study, the present findings suggest that the partial reinforcement strategy may be a viable means toward maintaining treatment gains over time with less active medication.

Sleep diaries of Vietnam War veterans with chronic PTSD: the relationships among insomnia symptoms, psychosocial stress, and nightmares.

Impaired sleep and nightmares are known symptoms of posttraumatic stress disorder (PTSD) in the veteran population. In order to assess prospectively the sleep disturbances in this population, sleep diaries are an effective way to obtain information over an extended period of time. In this investigation, a sample of veterans (N = 105) completed daily sleep diaries for a 6-week period. Greater PTSD severity and nightmare-related distress were correlated with more awakenings, shorter duration of sleep, longer sleep latency, and greater frequency of nightmares. Perceived frequency of daytime stressors was associated with an increased number of nightmares, nightmare-related distress, and longer sleep latency. The use of sleep diaries in future investigations may allow targeted treatments for veteran populations with PTSD and sleep disturbances.