Effects of sleep deprivation on nocturnal cytokine concentrations in depressed patients and healthy control subjects.

Previous studies have reported alterations of cytokine and cytokine-receptor concentrations in psychiatric patient populations, including patients with major depressive disorder (MDD). However, study results are conflicting, and possible causes for these abnormalities are unknown. Since sleep deprivation may induce a rapid improvement of mood in depressed patients, the authors investigated the impact of total sleep deprivation (TSD) for one night, and subsequent recovery sleep, on nocturnal concentrations of interleukin-6 (IL-6), interleukin-1-receptor antagonist (IL-1RA), and soluble IL-2 receptor (sIL-2R) in 15 unmedicated patients with MDD and 16 healthy volunteers. Whereas IL-6 levels normalized again during the recovery night in depressed patients, they were still elevated in control subjects. Serum levels of IL-1RA were higher in depressed patients than in controls, but were not affected by TSD. During recovery sleep, IL-1RA levels increased as compared with the preceding TSD night only in controls. Responders (N=8) differed from nonresponders (N=7) to TSD with regard to IL-1RA, which increased significantly during TSD in responders only. Sleep deprivation therefore seems to significantly affect cytokine levels in both depressed patients and healthy subjects, but does so in different ways. Sleep disturbances in depressed patients could account for the increased levels of cytokines found in these patients in several previous studies. The interaction between antidepressant effects of TSD and alterations of cytokines warrants further investigation.

No persisting effect of partial sleep curtailment on cognitive performance and declarative memory recall in adolescents.

Growing evidence indicates that sleep facilitates learning and memory processing. Sleep curtailment is increasingly common in adolescents. The aim of this study was to examine the effects of short-term sleep curtailment on declarative memory consolidation in adolescents. A randomized, cross-over study design was chosen. Twenty-two healthy subjects, aged 14-16 years, spent three consecutive nights in the sleep laboratory with a bedtime of 9 h during the first night (adaptation), 4 h during the second (partial sleep curtailment) and 9 h during the third night (recovery). The control condition consisted of three consecutive nights with bedtimes of 9 h. Both experimental conditions were separated by at least 3 weeks. The acquisition phase for the declarative tests was between 16:00 and 18:00 hours before the second night. Memory performance was examined in the morning after the recovery night. Executive function, attention and concentration were also assessed to control for any possible effects of tiredness. During the 4-h night, we observed a curtailment of 50% of non-rapid eye movement (non-REM), 5% of slow wave sleep (SWS) and 70% of REM sleep compared with the control night. Partial sleep curtailment of one night did not influence declarative memory retrieval significantly. Recall in the paired-associate word list task was correlated positively with percentage of non-REM sleep in the recovery night. Declarative memory consolidation does not appear to be influenced by short-term sleep curtailment in adolescents. This may be explained by the high ability of adolescents to compensate for acute sleep loss. The correlation between non-REM sleep and declarative memory performance supports earlier findings.

Effects of tryptophan depletion on cognitive functioning, obsessive-compulsive symptoms and mood in obsessive-compulsive disorder: preliminary results.

BACKGROUND: Previous studies suggest that obsessive-compulsive disorder (OCD) is associated with moderate cognitive deficits. There is also evidence for altered serotonergic transmission in OCD. The aim of this study was to evaluate the impact of rapid plasma tryptophan depletion on cognitive functioning in OCD. METHODS: A double-blind crossover study was conducted to explore the effects of tryptophan depletion on cognitive functioning, obsessive or compulsive (OC) symptoms and mood in OCD patients treated with selective serotonin reuptake inhibitors. RESULTS: After 5 h of tryptophan depletion, 6 out of 7 patients reported worsening of mood (placebo condition: 3 patients). No effect was found regarding OC symptoms. There was a small and nonsignificant improvement of nonverbal memory and fluency. Problem solving ability and verbal memory, in contrast, were slightly impaired after tryptophan depletion. The results, however, represented only tendencies without reaching significance. CONCLUSION: The results suggest that OC symptoms may not depend on the short-time availability of serotonin. As some critical cognitive functions improved following tryptophan depletion, there is no evidence from our study that neuropsychological impairment in OCD can be reduced to a lowered level of serotonin. Future studies are needed to further clarify these findings by use of larger samples.

Variability of periodic leg movements in various sleep disorders: implications for clinical and pathophysiologic studies.

STUDY OBJECTIVES: Periodic leg movements in sleep (PLMS) are a frequent phenomenon in various sleep disorders. The pathophysiology of PLMS is still not understood, but recent studies indicate a hypoactivity of the dopaminergic system in subjects with PLMS. In the present study, we investigated the intrasubject variance of PLMS from one night to the other because a fluctuation in the number of PLMS may influence the outcome of pharmacologic and pathophysiologic studies. DESIGN: Retrospective observational study. SETTING: Data collection occurred in the sleep disorders unit. PATIENTS: Sleep electroencephalogram and PLMS data of 115 patients with PLMS monitoring over 2 consecutive nights were evaluated retrospectively. Patients were grouped into the following diagnostic categories: restless legs syndrome, insomnia secondary to a psychiatric disorder, primary insomnia, sleep apnea syndrome, and narcolepsy or idiopathic hypersomnia. INTERVENTIONS: N/A. RESULTS: In 27% of the entire patient population, we found a considerable variability of the PLMS index (difference between nights > 10/hour) and, in 19% of patients, variability of the PLMS arousal index (difference between nights > 5/hour) across the 2 investigated nights. The intraindividual variance occurred most frequently and to the highest extent in patients with RLS. CONCLUSIONS: The variability of PLMS indexes should considered if the PLMS recording is performed in support of the clinical diagnosis or in the interpretation of studies investigating drug efficacy. Furthermore, the variability of PLMS may be an indicator of an instability of the dopaminergic system that should be taken into account in studies investigating central nervous system dopaminergic activity.

Impact of sleep-related complaints on depressive symptoms in patients with restless legs syndrome.

OBJECTIVE: Restless legs syndrome (RLS) is a distressing sensorimotor disorder with a 5% to 10% prevalence in the United States and Western Europe. The nocturnal occurrence of symptoms often leads to severe sleep disturbances. RLS has been reported to be associated with depression and anxiety. The aim of the present study was to investigate the relationship between RLS symptom severity, sleep disturbances, and depressive symptoms. METHOD: Questionnaire data from 100 consecutive patients with idiopathic RLS who had been investigated in our Sleep Disorders Unit from April 1999 to December 2004 were evaluated. Patients were untreated regarding RLS, depression, or sleep disturbances. Severity of RLS was assessed with the International RLS Study Group rating scale (IRLS). Depressive symptoms and subjective sleep quality were determined using the Beck Depression Inventory (BDI) and the Pittsburgh Sleep Quality Index (PSQI), respectively. RESULTS: IRLS scores indicated moderate-to-severe RLS symptoms in the population studied (mean +/- SD IRLS score = 23.6 +/- 6.7). The mean +/- SD BDI score was 9.3 +/- 5.6, with highest values on the "reduced sleep," "loss of energy," and "work difficulties" items, indicating predominating somatic symptoms of depression. Fourteen patients had a BDI score of 15 to 20 ("mild depression"), and 3 patients had a BDI score of 20 to 30 ("mild to moderate depression"). Overall, patients estimated their sleep quality as moderately impaired (mean +/- SD PSQI score = 10.9 +/- 3.7). Severity of RLS correlated with the impairment of subjective sleep quality (r = 0.281, p = .007) but not with self-rated depressive symptoms (r = 0.119, p = .237). CONCLUSION: RLS patients scored high on the somatic items of the BDI, particularly on those related to sleep disturbance, but not on the other items that mostly address cognitive symptoms. Our results indicate that RLS might be associated with some features of depression but not with the full spectrum of a depressive disorder. The relationship between the 2 disorders should be investigated in further studies.

The impact of increasing sleep restriction on cortisol and daytime sleepiness in adolescents.

Sleep restriction is a widespread phenomenon, specifically in adolescents. This study investigated the impact of increasing sleep restriction in adolescents on cortisol levels and daytime sleepiness. Eighty-eight healthy adolescents were randomized to five sleep restriction protocols (four consecutive nights with 9, 8, 7, 6, or 5 h time in bed). Polysomnography (baseline and last experimental night) and multiple sleep latency test (day 6) data were obtained. Saliva cortisol levels were assessed half-hourly in the evening before and in the morning after the baseline and the last experimental night. Four nights of sleep restriction in healthy adolescents lead to a linear increase of objective sleepiness, but had no significant effect on evening or morning cortisol levels. The lack of detrimental effects of sleep restriction on cortisol levels might be due to compensation mechanisms during sleep.

Sleep restriction over several days does not affect long-term recall of declarative and procedural memories in adolescents.

OBJECTIVES: There is broad evidence that sleep as opposed to waking facilitates the consolidation of both declarative and procedural memory. The current study addressed the question whether different extents of sleep restriction after learning would impair long-term memory consolidation in adolescents. METHODS: Eighty-eight healthy adolescents were randomized to five different sleep protocols with 9, 8, 7, 6 or 5 h of time in bed for four consecutive nights under controlled conditions that excluded daytime sleep. Declarative (word-pair task) and procedural memory (mirror tracing task) encoding was assessed prior to the sleep restriction protocol. Recall was assessed after two recovery nights following the sleep protocol and 4 weeks later. RESULTS: Sleep diaries and actigraphy data demonstrated that the participants closely followed the sleep protocols. There were no differences in demographic parameters or memory encoding at baseline. In contrast to the initial prediction, restriction of nocturnal sleep over four consecutive nights had no significant impact on declarative or procedural memory consolidation. Polysomnographic monitoring after sleep restriction demonstrated a high preservation of the amount of slow wave sleep in the restricted conditions. CONCLUSIONS: The results suggest that adolescents show a high resilience of memory consolidation to substantial sleep curtailment across four nights that might be promoted by increased sleep intensity under conditions of sleep restriction.

Sleep and memory in healthy children and adolescents - a critical review.

There is mounting evidence that sleep is important for learning, memory and the underlying neural plasticity. This article aims to review published studies that evaluate the association between sleep, its distinct stages and memory systems in healthy children and adolescents. Furthermore it intends to suggest directions for future research. A computerised search of the literature for relevant articles published between 1966 and March 2008 was performed using the keywords "sleep", "memory", "learn", "child", "adolescents", "adolescence" and "teenager". Fifteen studies met the inclusion criteria. Published studies focused on the impact of sleep on working memory and memory consolidation. In summary, most studies support the hypothesis that sleep facilitates working memory as well as memory consolidation in children and adolescents. There is evidence that performance in abstract and complex tasks involving higher brain functions declines more strongly after sleep deprivation than the performance in simple memory tasks. Future studies are needed to better understand the impact of a variety of variables potentially modulating the interplay between sleep and memory, such as developmental stage, socioeconomic burden, circadian factors, or the level of post-learning sensory and motor activity (interference). This line of research can provide valuable input relevant to teaching, learning and public health policy.