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Sleep and sleep regulation in the ferret (Mustela putorius furo).

We investigated sleep-wake (S-W) architecture and sleep regulation in the ferret: a phylogenetically primitive mammal increasingly used in neurobiological studies. Twenty-four hour S-W baseline data were collected in eight adult ferrets. Seven ferrets were then sleep deprived for 6h at the beginning of the light period. Like other placental mammals, ferrets exhibited the main vigilance states of wakefulness, rapid-eye-movement (REM) sleep and non-REM (NREM) sleep. Interestingly, the amount of REM sleep in the ferret was considerably higher (24.01+/-1.61% of total recording time) than typically reported in placental mammals. Ferret sleep was homeostatically regulated as sleep deprivation produced a significant increase in NREM EEG delta power during the recovery period. Therefore, ferret sleep in most respects is comparable to sleep in other placental mammals. However, the large amount of REM sleep in this phylogenetically more ancient species suggests that REM sleep may have been present in greater amounts in early stages of mammalian evolution.

Animals↗

Age-dependent changes in recovery sleep after 48 hours of sleep deprivation in rats.

To characterize possible changes in homeostatic regulation of sleep with aging, we have examined sleep stages during recovery sleep after 48 h of sleep deprivation in young (3 months), middle aged (12 months), and old (24 months) rats. It was found that young and middle aged, in contrast to old rats, had large (21-24%) increases in total sleep time during recovery sleep; the old rats experienced a quantitatively small (8%) but significant rise in total sleep. NREM sleep increased significantly during the recovery period in young and middle aged, but not older rats. High voltage NREM sleep (HS2) declined by 30% during recovery in the young animals, but remained unchanged compared to baseline in the middle aged and old animals. The young and middle aged rats had increases in REM sleep during recovery compared to their baseline by 96% and 93%, respectively, which was significantly greater than a 65% increase during recovery in the old rats. Increases in total sleep and REM sleep during recovery were largely confined to the first 6 h in young and middle aged rats, but maxima for the old rats occurred in the second 6 h.

Aging↗

Sleep and sleep substances.

Time-consuming studies in search of an endogenously occurring sleep substance started early in this century. The historical background of this field of sleep science is briefly reviewed. The search for "sleep-promoting substance (SPS)" started in 1972. A bioassay technique was developed based on the monitoring of the circadian sleep-waking rhythm in freely moving male rats. The partially purified SPS from the brainstem of 24-h sleep-deprived rats caused a reduction in locomotor activity and an increase in both slow wave sleep and paradoxical sleep, when nocturnally administered by either the intraperitoneal or intracerebroventricular route. SPS is composed of at least 4 different effective fractions, including uridine. The sleep-inducing and sleep-maintaining potencies of several putative sleep substances were compared. Circadian variations in their effectiveness were apparent. The role of sleep substances in sleep regulation is discussed.

Animals↗

Intrinsic dreams are not produced without REM sleep mechanisms: evidence through elicitation of sleep onset REM periods.

The hypothesis that there is a strict relationship between dreams and a specific rapid eye movement (REM) sleep mechanism is controversial. Many researchers have recently denied this relationship, yet none of their studies have simultaneously controlled both sleep length and depth prior to non-REM (NREM) and REM sleep awakenings, due to the natural rigid order of the NREM--REM sleep cycle. The failure to control sleep length and depth prior to arousal has confounded interpretations of the REM-dreams relationship. We have hypothesised that different physiological mechanisms underlie dreaming during REM and NREM sleep, based on recent findings concerning the specificity of REM sleep for cognitive function. Using the Sleep Interruption Technique, we elicited sleep onset REM periods (SOREMP) from 13 normal subjects to collect SOREMP and sleep onset NREM (NREMP) dreams without the confounds described above. Regression analyses showed that SOREMP dream occurrences were significantly related to the amount of REM sleep, while NREMP dream occurrences were related to arousals from NREM sleep. Dream properties evaluated using the Dream Property Scale showed qualitative differences between SOREMP and NREMP dream reports. These results support our hypothesis and we have concluded that although 'dreaming' may occur during both REM and NREM periods as previous researchers have suggested, the dreams obtained from these distinct periods differ significantly in their quantitative and qualitative aspects and are likely to be produced by different mechanisms.

Adolescent↗

Corticospinal excitability and sleep: a motor threshold assessment by transcranial magnetic stimulation after awakenings from REM and NREM sleep.

Transcranial magnetic stimulation (TMS) is a recently established technique in the neurosciences that allows the non-invasive assessment, among other parameters, of the excitability of motor cortex. Up to now, its application to sleep research has been very scarce and because of technical problems it provided contrasting results. In fact delivering one single suprathreshold magnetic stimulus easily awakes subjects, or lightens their sleep. For this reason, in the present study we assessed motor thresholds (MTs) upon rapid eye movement (REM) and non-rapid eye movement (NREM) sleep awakenings, both in the first and in the last part of the night. Taking into account that a full re-establishment of wake regional brain activity patterns upon awakening from sleep needs up to 20-30 min, it is possible to make inferences about the neurophysiological characteristics of the different sleep stages by analyzing the variables of interest immediately after provoked awakenings. Ten female volunteers slept in the lab for four consecutive nights. During the first night the MTs were collected, following a standardized procedure: 5 min before lights off, upon stage 2 awakening (second NREM period), upon REM sleep awakening (second REM period), upon the final morning awakening (always from stage 2). Results showed that MTs increased linearly from presleep wakefulness to REM sleep awakenings, and from the latter to stage 2 awakenings. There was also a time-of-night effect on MTs upon awakening from stage 2, indicating that MTs decreased from the first to the second part of the night. The increase in corticospinal excitability across the night, which parallels the fulfillment of sleep need, is consistent with the linear decrease of auditory arousal thresholds during the night. The maximal reduction of corticospinal excitability during early NREM sleep can be related to the hyperpolarization of thalamocortical neurons, and is in line with the decreased metabolic activity of motor cortices during this sleep stage. On the contrary, the increase of MTs upon REM sleep awakenings should reflect peripheral factors. We conclude that our findings legitimate the introduction of the TMS technique as a new proper tool in sleep research.

Adult↗

Objective and subjective sleep quality in premenopausal, perimenopausal, and postmenopausal women in the Wisconsin Sleep Cohort Study.

STUDY OBJECTIVE: Assess objectively measured sleep quality in premenopausal, perimenopausal, and postmenopausal women. DESIGN: Observational epidemiology study. SETTING: Community-based. PARTICIPANTS: Probability sample of 589 premenopausal, perimenopausal, and postmenopausal women recruited from state employee records. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Menopausal status was determined by menstrual history, surgical history, and use of hormone replacement therapy. Sleep quality was objectively measured by full in-laboratory polysomnography and by self-reported sleep problems. Linear and logistic regression were used to estimate associations adjusted for potential confounding factors. OBJECTIVE: Sleep quality was not worse in perimenopausal or postmenopausal women, compared with premenopausal women. To the contrary, postmenopausal woman had more deep sleep (16% vs 13% stages 3/4, P < 0.001) and significantly longer total sleep time (388 minutes vs 374 minutes, P = 0.05). Menopausal status was moderately related to self-reported dissatisfaction with sleep but was not consistently associated with symptoms of insomnia or sleepiness. CONCLUSIONS: Menopause is not associated with diminished sleep quality measured by polysomnography. Although perimenopausal and postmenopausal women, relative to premenopausal women, were less satisfied with their sleep, menopause was not a strong predictor of specific sleep-disorder symptoms. Symptoms and signs of sleep abnormalities in midlife women should not be attributed primarily to menopause before ruling out underlying sleep disorders.

Adult↗

Deletion of the mammalian circadian clock gene BMAL1/Mop3 alters baseline sleep architecture and the response to sleep deprivation.

STUDY OBJECTIVES: The finding that deletion or mutation of core circadian clock genes in both mice and flies induce unexpected alterations in sleep amount, sleep architecture and the recovery response to sleep deprivation, has led to new insights into functions of the circadian system that extend beyond its role as a regulator of the timing of the sleep-wake cycle. A key transcription factor in the transcriptional/translational feedback loop of mammalian circadian genes is BMAL1/Mop3, a heterodimeric partner to CLOCK. It was previously shown that mice deficient in the BMAL1/Mop3 gene become immediately arrhythmic in constant darkness and have reduced locomotor activity levels under entrained and constant conditions. In this study, we tested the hypothesis that the mammalian BMAL1/Mop3 gene would have regulatory effects on sleep-wake patterns. DESIGN: In mice with targeted deletion of the BMAL1/Mop3 gene, EEG/EMG sleep-wake patterns were recorded under entrained and free-running conditions as well as following acute (6-hrs) sleep deprivation. MEASUREMENTS AND RESULTS: Mice homozygous for the BMAL1/Mop3 deletion showed an attenuated rhythm of sleep and wakefulness distribution across the 24-hr period. In addition, these mice showed increases in total sleep time, sleep fragmentation and EEG delta power under baseline conditions, and an attenuated compensatory response to acute sleep deprivation. CONCLUSIONS: These new data strengthen the hypothesis that molecular components of the circadian system play a central role in the generation of sleep and wakefulness beyond just the timing of these behavioral vigilance states.

ARNTL Transcription Factors↗

Understanding sleep-wake behavior and sleep disorders in children: the value of a model.

PURPOSE OF REVIEW: Sleep-wake problems such as night wakings, excessive crying, or difficulties in falling asleep are frequent behavioral issues during childhood. Maturational changes in sleep and circadian regulation likely contribute to the development and maintenance of such problems. This review highlights the recent research examining bioregulatory sleep mechanisms during development and provides a model for predicting sleep-wake behavior in young humans. RECENT FINDINGS: Findings demonstrate that circadian and sleep homeostatic processes exhibit maturational changes during the first two decades of life. The developing interaction of both processes may be a key determinant of sleep-wake and crying behavior in infancy. Evidence shows that the dynamics of sleep homeostatic processes slow down in the course of childhood (i.e., sleep pressure accumulates more slowly with increasing age) enabling children to be awake for consolidated periods during the day. Another current topic is the adolescent sleep phase delay, which appears to be driven primarily by maturational changes in sleep homeostatic and circadian processes. SUMMARY: The two-process model of sleep regulation is a valuable framework for understanding and predicting sleep-wake behavior in young humans. Such knowledge is important for improving anticipatory guidance, parental education, and patient care, as well as for developing appropriate social policies.

Adolescent↗

Association of nocturnal arrhythmias with sleep-disordered breathing: The Sleep Heart Health Study.

RATIONALE: Sleep-disordered breathing recurrent intermittent hypoxia and sympathetic nervous system activity surges provide the milieu for cardiac arrhythmia development. OBJECTIVE: We postulate that the prevalence of nocturnal cardiac arrhythmias is higher among subjects with than without sleep-disordered breathing. METHODS: The prevalence of arrhythmias was compared in two samples of participants from the Sleep Heart Health Study frequency-matched on age, sex, race/ethnicity, and body mass index: (1) 228 subjects with sleep-disordered breathing (respiratory disturbance index>or=30) and (2) 338 subjects without sleep-disordered breathing (respiratory disturbance index<5). RESULTS: Atrial fibrillation, nonsustained ventricular tachycardia, and complex ventricular ectopy (nonsustained ventricular tachycardia or bigeminy or trigeminy or quadrigeminy) were more common in subjects with sleep-disordered breathing compared with those without sleep-disordered breathing: 4.8 versus 0.9% (p=0.003) for atrial fibrillation; 5.3 versus 1.2% (p=0.004) for nonsustained ventricular tachycardia; 25.0 versus 14.5% (p=0.002) for complex ventricular ectopy. Compared with those without sleep-disordered breathing and adjusting for age, sex, body mass index, and prevalent coronary heart disease, individuals with sleep-disordered breathing had four times the odds of atrial fibrillation (odds ratio [OR], 4.02; 95% confidence interval [CI], 1.03-15.74), three times the odds of nonsustained ventricular tachycardia (OR, 3.40; 95% CI, 1.03-11.20), and almost twice the odds of complex ventricular ectopy (OR, 1.74; 95% CI, 1.11-2.74). A significant relation was also observed between sleep-disordered breathing and ventricular ectopic beats/h (p<0.0003) considered as a continuous outcome. CONCLUSIONS: Individuals with severe sleep-disordered breathing have two- to fourfold higher odds of complex arrhythmias than those without sleep-disordered breathing even after adjustment for potential confounders.

Aged↗

Determination of sleep latency in polysomnographic evaluations of daytime somnolence in patients with sleep apnea and patients with narcolepsy.

Sleep onset during the multiple sleep latency test was scored by three criteria for 21 patients with narcolepsy and 21 patients with obstructive sleep apnea: a single epoch of stage 1, three consecutive epochs of stage 1, and a single epoch of stage 2 or REM. Mean sleep latency for both groups was predictably shortest using a single epoch of stage 1 and longest using a single epoch of stage 2 or REM. All estimates of sleep latency were highly correlated. It was concluded that a single epoch of any stage of sleep is an appropriate measure of sleep latency for patients with narcolepsy, although a modified scoring system should be developed for patients with sleep apnea. The obstructive apneic episodes prevented or delayed sleep onset on 4.8% to 33.3% of trials depending on the specific criteria used to determine sleep latency. Such apnea-related interruptions to sleep should be taken into account when assessing daytime somnolence in patients with sleep apnea.

Adolescent↗

Sleep structure correlates of continuous positive airway pressure variations during application of an autotitrating continuous positive airway pressure machine in patients with obstructive sleep apnea syndrome.

STUDY OBJECTIVES: To evaluate the relationship between sleep structure and continuous positive airway pressure (CPAP) delivered by an automatic CPAP (auto-CPAP) machine in patients with obstructive sleep apnea syndrome (OSAS). DESIGN: Nocturnal polysomnography was performed during CPAP administration by an auto-CPAP machine (Autoset Clinical 1; ResMed; Sydney, Australia). SETTING: Sleep-disorders center in a research institute. PATIENTS: Fifteen subjects with newly diagnosed OSAS deserving home CPAP treatment. MEASUREMENTS AND RESULTS: During the night, in most cases, the lowest CPAP level was recorded during a prolonged nonrapid eye movement (NREM) sleep period uninterrupted by arousals, whereas the highest level during wake-sleep transitions or NREM sleep fragmented by arousals. In four subjects, rapid eye movement sleep was always associated with increasing CPAP. Sleep efficiency was negatively correlated with CPAP variability, evaluated as the SD of the mean nocturnal CPAP level averaged epoch by epoch (r = 0.63, p < 0.02). Eighty-eight percent of rapid CPAP augmentations (increases by at least 2 cm H(2)O in less-than-or-equal 2 min) were observed during sleep-wake transitions or after arousals/awakenings (Ar/Aw); 63% of such Ar/Aw were not preceded by any detectable respiratory abnormality. CONCLUSIONS: CPAP levels and variations during auto-CPAP application may be mainly related to sleep continuity and efficiency. The recording of a highly variable pressure during auto-CPAP administration in an unattended environment must raise the question whether the patient's sleep quality was acceptable. A poor sleep quality during an autotitration night could lead to an undesirable overestimation of the CPAP level needed for use with fixed-level CPAP machines.

Adult↗

Practice parameters for the evaluation of chronic insomnia. An American Academy of Sleep Medicine report. Standards of Practice Committee of the American Academy of Sleep Medicine.

Chronic insomnia is the most common sleep complaint which health care practitioners must confront. Most insomnia patients are not, however, seen by sleep physicians but rather by a variety of primary care physicians. There is little agreement concerning methods for effective assessment and subsequent differential diagnosis of this pervasive problem. The most common basis for diagnosis and subsequent treatment has been the practitioner's clinical impression from an unstructured interview. No systematic, evidence-based guidelines for diagnosis exist for chronic insomnia. This practice parameter paper presents recommendations for the evaluation of chronic insomnia based on the evidence in the accompanying review paper. We recommend use of these parameters by the sleep community, but even more importantly, hope the large number of primary care physicians providing this care can benefit from their use. Conclusions reached in these practice parameters include the following recommendations for the evaluation of chronic insomnia. Since the complaint of insomnia is so widespread and since patients may overlook the impact of poor sleep quality on daily functioning, the health care practitioner should screen for a history of sleep difficulty. This evaluation should include a sleep history focused on common sleep disorders to identify primary and secondary insomnias. Polysomnography, and the Multiple Sleep Latency Test (MSLT) should not be routinely used to screen or diagnose patients with insomnia complaints. However, the complaint of insomnia does not preclude the appropriate use of these tests for diagnosis of specific sleep disorders such as obstructive sleep apnea, periodic limb movement disorder, and narcolepsy that may be present in patients with insomnia. There is insufficient evidence to suggest whether portable sleep studies, actigraphy, or other alternative assessment measures including static charge beds are effective in the evaluation of insomnia complaints. Instruments such as sleep logs, self-administered questionnaires, symptom checklist, or psychological screening tests may be of benefit to discriminate insomnia patients from normals, but these instruments have not been shown to differentiate subtypes of insomnia complaints.

Chronic Disease↗

Short-term variability of respiration and sleep during unattended nonlaboratory polysomnography--the Sleep Heart Health Study. [corrected].

STUDY OBJECTIVES: To determine the short-term variability of indices of disturbed respiration and sleep during 2 nights of unattended nonlaboratory polysomnography conducted several months apart. DESIGN: Participants were randomly selected using a block design with stratification on preliminary estimates of 2 criteria: respiratory disturbance index [RDI3% (apnea or hypopnea events associated with > or = 3% O2 desaturation): < 15/hour total sleep time, > or = 15/hour total sleep time] and sleep efficiency (SEff: < 85% and > or = 85%). The RDI and sleep data from initial and repeated polysomnography were compared. SETTING: NA. PARTICIPANTS: A subset of 99 participants in the Sleep Heart Health Study who agreed to have a repeat polysomnogram within 4 months of their original study. INTERVENTIONS: NA. MEASUREMENTS AND RESULTS: Acceptable repeat polysomnograms were obtained in 91 subjects (mean study interval: 77 +/- 18 [sd] days; range: 31-112 days). There was no significant bias in RDI between study nights using several different RDI definitions including RDI3% and RDI4% (apnea or hypopnea events associated with > or = 4% O2 desaturation). Variability between studies estimated using intraclass correlations (ICC) ranged from 0.77 to 0.81. For subjects with a RDI3% < 15, variability increased as a function of increasing RDI, but for those with a RDI3% > or = 15, variability was constant. Body mass index, SEff, gender, or age did not directly predict RDI variability. Using RDI4% cutpoints of < or = 5, < or = 10 and < or = 15 events per hour of sleep demonstrated that 79.1%, 85.7%, and 87.9% of subjects, respectively, had the same classification of SDB status on both nights of study. There also was no significant bias in sleep staging, sleep efficiency, or arousal index between studies. However, variability was greater with ICC values ranging from 0.37 (% time in REM) to 0.76 (arousal index). CONCLUSION: In the Sleep Heart Health Study, accurate estimates of the severity of sleep-disordered breathing and the quality of sleep were obtained from a single night of unattended nonlaboratory polysomnography. These findings may be applicable to other large epidemiologic studies provided that similar recording techniques and quality-assurance procedures are followed.

Adult↗

Study of delta sleep-inducing peptide efficacy in improving sleep on short-term administration to chronic insomniacs.

The effects of delta sleep-inducing peptide (DSIP), on the sleep cycle of insomniac patients were assessed by means of polysomnographic recordings. DSIP in a dose of 25 nmol/kg or a placebo was administered i.v. during four nights using a double-blind crossover design. The number of nocturnal awakenings, non-rapid-eye-movement (NREM) sleep latency, total waking time and waking time after sleep onset were decreased under DSIP treatment, but no significant differences were found in comparison to baseline or to double-blind placebo nights. Total sleep time and NREM sleep time were increased by the peptide. Their increase was related to increases in stage 2, while stage 1, slow wave sleep (stages 3 and 4) and rapid-eye-movement sleep were not modified. For NREM sleep time and stage 2 sleep differences between DSIP and a placebo were significant, but the same differences existed already for the baseline values. It can be concluded that sleep improvement under DSIP treatment is of little clinical significance.

Adult↗

A 20-h recovery sleep after prolonged sleep restriction: some effects of competing in a world record-setting cinemarathon.

The recovery sleep of a 21-year-old normal woman was assessed after she had endured 11(1/2) days of sleep restriction in a world record-setting film-viewing marathon. An exceptional sleep debt was observed as indicated by an instanteous sleep onset, a high sleep efficiency, and a total sleep duration of over 20 hours. Other striking features of this recovery sleep were very short latencies to stages 3 and 4 sleep, return of Stage 4 sleep after 14.5 h, REM and SWS sleep rebound, and a linear increase in REM sleep efficiency across 14 consecutive REM-NREM episodes. Seven of nine home dreams reported after this recording contained competition themes, but none relating to the marathon films. Comparisons of the present results with those from subjects in previous record-setting events suggest possible explanations for the extremely long recovery sleep. Results also suggest that analyses of multiple consecutive sleep cycles may provide novel ways of assessing hypotheses about regulation of the REM-NREM cycle.

Journal Article↗

Motor dyscontrol in narcolepsy: rapid-eye-movement (REM) sleep without atonia and REM sleep behavior disorder.

Narcolepsy involves abnormalities of rapid-eye-movement (REM) sleep, including a short latency to the onset of REM sleep, hypnagogic hallucinations, and sleep paralysis. In addition, persistence of muscle tone by electromyographic criteria or excessive muscle twitching during REM sleep or both have been reported in treated and untreated narcoleptic patients. We report that another previously described abnormality of REM sleep, REM sleep behavior disorder, may also be a symptom of narcolepsy. This disorder was found in 10 narcoleptic patients during routine clinical evaluations involving polysomnography and multiple sleep latency tests. During REM sleep, 7 additional narcoleptic patients displayed persistent muscle tone and/or excessive twitching, which we believe to be subclinical components of REM sleep behavior disorder. These 17 patients, diagnosed by established criteria for narcolepsy and for REM sleep behavior disorder, ranged in age from 8 to 74 years. Seventy-one percent were male. Narcolepsy and REM sleep behavior disorder most commonly emerged in tandem. In 3 patients, treatment of narcolepsy-cataplexy with stimulants and tricyclics either induced or exacerbated REM sleep behavior disorder.

Adolescent↗

Effects of kava-kava extract on the sleep-wake cycle in sleep-disturbed rats.

RATIONALE: Kava-kava extract may be useful as an herbal medicine for treatment of insomnia and anxiety. OBJECTIVES: The present study was undertaken to investigate the effects of kava-kava extract on the sleep-wake cycle in comparison with that of flunitrazepam using sleep-disturbed rats. METHODS: Electrodes for measurement of electroencephalogram (EEG) and electromyogram (EMG) were implanted into the frontal cortex and the dorsal neck muscle of rats. EEG and EMG were recorded with an electroencephalogram. SleepSign ver.2.0 was used for EEG and EMG analysis. Total times of wakefulness, non-rapid eye movement (non-REM) and REM sleep were measured from 09:00 to 15:00. RESULTS: A significant shortening of the sleep latency in sleep-disturbed rats was observed following the administration of kava-kava extract at a dose of 300 mg/kg, while no effects were observed on the total waking and non-REM sleep time. On the other hand, flunitrazepam showed a significant shortening in sleep latency, decrease in total waking time and increase in total non-REM sleep time. Although the effects of flunitrazepam were antagonized by the benzodiazepine receptor antagonist flumazenil, the effect of kava-kava extract was not antagonized by flumazenil. Kava-kava extract showed a significant increase in delta activity during non-REM sleep in sleep-disturbed rats, whereas a significant decrease in delta power during non-REM sleep was observed with flunitrazepam. Flumazenil caused no significant effect on the changes in delta activity induced by both kava-kava extract and flunitrazepam. CONCLUSIONS: Kava-kava extract is an herbal medicine having not only hypnotic effects, but also sleep quality-enhancement effects.

Animals↗

Sleep electroencephalogram in seasonal affective disorder and in control women: effects of midday light treatment and sleep deprivation.

The role of sleep regulation in Seasonal Affective Disorder (SAD) was studied in 11 female SAD patients and eight controls in winter before and after light treatment (LT, 6000 lux, 10-14h, 5 days). The sleep electroencephalogram (EEG) was recorded at baseline and after the total sleep deprivation (TSD) of a 40-h constant routine. The well-known effects of TSD on sleep parameters and on EEG power spectra were replicated, indicating normal homeostatic sleep regulation in SAD. Sleep improved after LT in both groups. Since the condition following LT was the second session, these improvements may be an order effect and/or an effect of LT itself. After LT, sleep EEG spectra of SAD patients, but not of controls, showed modifications resembling those of recovery sleep. Since only SAD patients curtailed their sleep while remitting during the LT period, these EEG modifications can be explained by normal sleep regulation alone. We conclude that the robust antidepressant effect of LT in SAD is unlikely to be mediated by changes in sleep, and that sleep regulatory mechanisms are not a crucial factor in the pathogenesis of winter depression.

Adult↗