SLEEP

Taylor, Daniel J.

doi: 10.1093/sleep/31.4.447pmid: 18457230

Zammit, Gary K.

doi: 10.1093/sleep/31.4.449pmid: 18457231

Svetnik, Vladimir; Ma, Junshui; Soper, Keith A.; Doran, Scott; Renger, John J.; Deacon, Steve; Koblan, Ken S.

doi: 10.1093/sleep/31.4.451pmid: N/A

Watson, Christopher J.; Soto-Calderon, Haideliza; Lydic, Ralph; Baghdoyan, Helen A.

doi: 10.1093/sleep/31.4.453pmid: 18457232

AbstractStudy Objectives:GABAergic transmission in the oral part of the pontine reticular formation (PnO) increases wakefulness. The hypothalamic peptide hypocretin-1 (orexin A) promotes wakefulness, and the PnO receives hypocretinergic input. The present study tested the hypothesis that PnO administration of hypocretin-1 increases PnO GABA levels and increases wakefulness. This study also tested the hypothesis that wakefulness is either increased or decreased, respectively, by PnO administration of drugs known to selectively increase or decrease GABA levels.Design:A within-subjects design was used for microdialysis and microinjection experiments.Setting:University of Michigan.Patients or Participants:Experiments were performed using adult male Crl:CD® (SD)IGS BR (Sprague-Dawley) rats (n = 46).Interventions:PnO administration of hypocretin-1, nipecotic acid (a GABA uptake inhibitor that increases extracellular GABA levels), 3-mer-captopropionic acid (a GABA synthesis inhibitor that decreases extracellular GABA levels; 3-MPA), and Ringer solution (vehicle control).Measurements and Results:Dialysis administration of hypocretin-1 to the PnO caused a statistically significant, concentration-dependent increase in PnO GABA levels. PnO microinjection of hypocretin-1 or nipecotic acid caused a significant increase in wakefulness and a significant decrease in non-rapid eye movement (NREM) sleep and REM sleep. Mi-croinjecting 3-MPA into the PnO caused a significant increase in NREM sleep and REM sleep and a significant decrease in wakefulness.Conclusions:An increase or a decrease in PnO GABA levels causes an increase or decrease, respectively, in wakefulness. Hypocretin-1 may promote wakefulness, at least in part, by increasing GABAergic transmission in the PnO.

Wu, Mark N.; Koh, Kyunghee; Yue, Zhifeng; Joiner, William J.; Sehgal, Amita

doi: 10.1093/sleep/31.4.465pmid: 18457233

AbstractStudy Objectives:In order to characterize the genetic mechanisms underlying sleep, we have carried out a large-scale screen in Drosophila to identify short-sleeping mutants. The objectives of this study were as follows: (1) characterize the phenotypes of the shortest-sleeping mutants; (2) examine whether changes in arousal threshold or sleep homeostasis underlie short-sleeping phenotypes; (3) clone a gene affected in one of the shortest sleepers; and (4) investigate whether circadian mutants can be identified using light:dark (L:D) locomotor data obtained for studying sleep behavior.Design:Locomotor activity was measured using the Drosophila Activity Monitoring System in a 12:12 L:D cycle.Setting:Drosophila research laboratory.Participants:Adult flies from the 2nd chromosome Zuker collection, which contain mutations in most of the nonessential genes on the Drosophila 2nd chromosome.Measurements and Results:Our analysis of sleep characteristics suggests that daily activity (but not waking activity) correlates with daily sleep time and that defects in sleep maintenance are more common than defects in sleep initiation. Our shortest sleepers have intact or increased sleep rebound following sleep deprivation but show reduced thresholds for arousal. Molecular analysis of one of the short-sleeping lines indicates that it is a novel allele of a dopamine transporter (DAT). Finally, we describe a novel approach for identifying circadian mutants using L:D data.Conclusions:Our data suggest that most short-sleeping mutant phenotypes in Drosophila are characterized by an inability to stay asleep, most likely because of a reduced arousal threshold.

Buysse, Daniel J.; Angst, Jules; Gamma, Alex; Ajdacic, Vladeta; Eich, Dominique; Rössler, Wulf

doi: 10.1093/sleep/31.4.473pmid: 18457234

AbstractStudy Objectives:(1) To describe the prevalence and prospective course of insomnia in a representative young-adult sample and (2) to describe the cross-sectional and longitudinal associations between insomnia and depression.Design:Longitudinal cohort study.Setting:Community of Zurich, Switzerland.Participants:Representative stratified population sample.Interventions:None.Measurements and Results:The Zurich Study prospectively assessed psychiatric, physical, and sleep symptoms in a community sample of young adults (n = 591) with 6 interviews spanning 20 years. We distinguished 4 duration-based subtypes of insomnia: 1-month insomnia associated with significant distress, 2- to 3-week insomnia, recurrent brief insomnia, and occasional brief insomnia. The annual prevalence of 1-month insomnia increased gradually over time, with a cumulative prevalence rate of 20% and a greater than 2-fold risk among women. In 40% of subjects, insomnia developed into more chronic forms over time. Insomnia either with or without comorbid depression was highly stable over time. Insomnia lasting 2 weeks or longer predicted major depressive episodes and major depressive disorder at subsequent interviews; 17% to 50% of subjects with insomnia lasting 2 weeks or longer developed a major depressive episode in a later interview. “Pure” insomnia and “pure” depression were not longitudinally related to each other, whereas insomnia comorbid with depression was longitudinally related to both.Conclusions:This longitudinal study confirms the persistent nature of insomnia and the increased risk of subsequent depression among individuals with insomnia. The data support a spectrum of insomnia (defined by duration and frequency) comorbid with, rather than secondary to, depression.

Pigeon, Wilfred R.; Hegel, Mark; Unützer, Jürgen; Fan, Ming-Yu; Sateia, Michael J.; Lyness, Jeffrey M.; Phillips, Cindy; Perlis, Michael L.

doi: 10.1093/sleep/31.4.481pmid: 18457235

AbstractStudy Objectives:Insomnia and depressive disorders are significant health problems in the elderly. Persistent insomnia is a risk factor for the development of new-onset and recurrent major depressive disorder (MDD). Less clear is whether persistent insomnia may perpetuate MDD and/or dysthymia. The present longitudinal study examines the relationship of insomnia to the continuation of depression in the context of an intervention study in elderly subjects.Design:Data were drawn from Project IMPACT, a multisite intervention study, which enrolled 1801 elderly patients with MDD and/or dysthymia. In the current study, subjects were assigned to an insomnia-status group (Persistent, Intermediate, and No Insomnia) based on insomnia scores at both baseline and 3-month time points. Logistic regressions were conducted to determine whether Persistent Insomnia was prospectively associated with increased risk of remaining depressed and/or achieving a less than 50% clinical improvement at 6 and at 12 months compared with the No Insomnia reference group. The Intermediate Insomnia group was compared with the other 2 groups to determine whether a dose-response relationship existed between insomnia type and subsequent depression.Setting:Eighteen primary clinics in 5 states.Participants:Older adults (60+) with depression.Measurements and Results:Overall, patients with persistent insomnia were 1.8 to 3.5 times more likely to remain depressed, compared with patients with no insomnia. The findings were more robust in patients receiving usual care for depression than in patients receiving enhanced care. Findings were also more robust in subjects who had MDD as opposed to those with dysthymia alone.Conclusions:These findings suggest that, in addition to being a risk factor for a depressive episode, persistent insomnia may serve to perpetuate the illness in some elderly patients and especially in those receiving standard care for depression in primary care settings. Enhanced depression care may partially mitigate the perpetuating effects of insomnia on depression.

Manber, Rachel; Edinger, Jack D.; Gress, Jenna L.; Pedro-Salcedo, Melanie G. San; Kuo, Tracy F.; Kalista, Tasha

doi: 10.1093/sleep/31.4.489pmid: 18457236

AbstractStudy Objective:Insomnia impacts the course of major depressive disorder (MDD), hinders response to treatment, and increases risk for depressive relapse. This study is an initial evaluation of adding cognitive behavioral therapy for insomnia (CBTI) to the antidepressant medication escitalopram (EsCIT) in individuals with both disorders.Design and setting:A randomized, controlled, pilot study in a single academic medical center.Participants:30 individuals (61% female, mean age 35±18) with MDD and insomnia.Interventions:EsCIT and 7 individual therapy sessions of CBTI or CTRL (quasi-desensitization).Measurements and results:Depression was assessed with the HRSD17 and the depression portion of the SCID, administered by raters masked to treatment assignment, at baseline and after 2, 4, 6, 8, and 12 weeks of treatment. The primary outcome was remission of MDD at study exit, which required both an HRSD17 score ≤ 7 and absence of the 2 core symptoms of MDD. Sleep was assessed with the insomnia severity index (ISI), daily sleep diaries, and actigraphy. EsCIT + CBTI resulted in a higher rate of remission of depression (61.5%) than EsCIT + CTRL (33.3%). EsCIT + CBTI was also associated with a greater remission from insomnia (50.0%) than EsCIT + CTRL (7.7%) and larger improvement in all diary and actigraphy measures of sleep, except for total sleep time.Conclusion:This pilot study provides evidence that augmenting an antidepressant medication with a brief, symptom focused, cognitive-behavioral therapy for insomnia is promising for individuals with MDD and comorbid insomnia in terms of alleviating both depression and insomnia.

Madan, Vibha; Brennan, Francis X.; Mann, Graziella L.; Horbal, Apryle A.; Dunn, Gregory A.; Ross, Richard J.; Morrison, Adrian R.

doi: 10.1093/sleep/31.4.497pmid: 18457237

AbstractStudy Objectives:To study long-term effects of conditioned fear on REM sleep (REMS) parameters in albino rats.Design:We have investigated disturbances in sleep architecture, including muscle twitch density as REMS phasic activity, and freezing behavior in wakefulness, upon reexposure to a conditioned stimulus (CS) on Day 1 and Day 14 postconditioning.Subjects:Male Sprague-Dawley rats prepared for polysomnographic recordings.Interventions:After baseline sleep recording, the animals in the experimental group received five pairings of a 5-sec tone, co-terminating with a 1-sec, 1 mA footshock. The control rats received similar numbers of tones and shocks, but explicitly unpaired. On postconditioning days, after reexposure to tones alone, sleep and freezing behavior were recorded.Measurements and Results:Conditioned fear significantly altered REMS microarchitecture (characterized as sequential-REMS [seq-REMS: ≤3 min episode separation] and single-REMS [sin-REMS: >3 min episode separation]) on Day 14. The total amount and number of seq-REMS episodes decreased, while the total amount and number of sin-REMS episodes increased. Further, the CS induced significant increases in freezing and REMS myoclonic twitch density in the experimental group. Reexposure to the CS produced no alterations in controls.Conclusions:The results suggest that conditioned fear causes REMS alterations, including difficulty in initiating a REMS episode as indicated by the diminution in the number of seq-REMS episodes. Another finding, the increase in phasic activity, agrees with the inference from clinical investigations that retrieval of fearful memories can be associated with the long-term REMS disturbances characteristic of posttraumatic stress disorder.

Tiba, Paula Ayako; de Menezes Oliveira, Maria Gabriela; Rossi, Vanessa Contatto; Tufik, Sergio; Suchecki, Deborah

doi: 10.1093/sleep/31.4.505pmid: 18457238

AbstractStudy Objectives:To evaluate whether paradoxical sleep deprivation-induced memory impairments are due to release of glucocorticoids, by means of corticosterone inhibition with metyrapone.Design:The design was a 2 (Groups [control, paradoxical sleep-deprived]) × 2 (Treatments [vehicle, metyrapone]) study, performed in 2 experiments: Acute treatment (single injection given immediately after 96 hours of sleep deprivation) and chronic treatment (8 injections, twice per day, throughout the sleep-deprivation period). Animals were either paradoxical sleep-deprived or remained in their home cages for 96 hours before training in contextual fear conditioning and received intraperitoneal injections of a corticosterone synthesis inhibitor, metyrapone. Memory performance was tested 24 hours after training.Subjects:Three-month old Wistar male rats.Measurements:Freezing behavior was considered as the conditioning index, and adrenocorticotropic hormone and corticosterone plasma levels were determined from trunk blood of animals sacrificed in different time points. Animals were weighed before and after the paradoxical sleep-deprivation period.Results:Acute metyrapone treatment impaired memory in control animals and did not prevent paradoxical sleep deprivation-induced memory impairment. Likewise, in the chronic treatment, paradoxical sleep-deprived animals did not differ from control rats in their corticosterone or adrenocorticotropic hormone response to training, but still did not learn as well, and did not show any stress responses to the testing. Chronic metyrapone was, however, effective in preventing the weight loss typically observed in paradoxical sleep-deprived animals.Conclusions:Our results suggest that glucocorticoids do not mediate memory impairments but might be responsible for the weight loss induced by paradoxical sleep deprivation.