Epigenetic dysregulation of genes related to synaptic long-term depression among adolescents with depressive disorder and sleep symptoms.

OBJECTIVES: This study aimed to test the hypothesis that sleep and depression have independent effects on brain development and plasticity in adolescents, and that these changes are reflected in changes in the epigenome. METHODS: Participants were 17 medication-free adolescent boys (age 16.05 ± 0.80 years, mean ± standard deviation (SD); eight cases with depression and sleep symptoms, nine healthy controls). Sleep was assessed by polysomnography recordings and the Pediatric Daytime Sleepiness Scale (PDSS) and Athens Insomnia Scale (AIS). Participants underwent a clinical evaluation. DNA methylation of blood leukocytes was measured by Illumina 450K array, and Ingenuity Pathway analysis was applied to identify the most significant pathways with differentially methylated positions (DMPs). Secondary analysis of the identified loci included linear correlations between methylation and the subjectively rated scales of sleep, depression and sleep microarchitecture. RESULTS: Due to small sample size, we found no genome-wide significant differences in methylation between cases and controls. However, pathway analysis identified the synaptic long-term depression (LTD) canonical pathway (p = 0.00045) when the best 500 DMPs from the original case-control design were included. A flattened dissipation of slow wave sleep, tiredness and depression severity values correlated with five of 10 sites from the LTD pathway (IGF1R, PLAG16, PLA2R1, PPP2C5 and ERK12) in the secondary analysis when the case-control status was controlled for. CONCLUSION: Among adolescents, depressive disorder with sleep symptoms is associated with a distinctive epigenetic pattern of DNA methylation in blood leukocytes. The enrichment of DMPs on genes related to synaptic LTD emphasizes the role of sleep in synaptic plasticity and the widespread physiological consequences of disturbed sleep.

Trends in self-reported sleep problems, tiredness and related school performance among Finnish adolescents from 1984 to 2011.

The aim of this study was to investigate long-term trends in insomnia symptoms, tiredness and school performance among Finnish adolescents. A time-series from 1984 to 2011 was analysed from two large-scale survey studies, the Finnish School Health Promotion Study and the Health Behavior in School-Aged Children study. A total of 1,136,583 adolescents aged 11-18 years answered a standardized questionnaire assessing frequency of insomnia symptoms, tiredness and school performance. A clear approximately twofold increasing trend in insomnia symptoms and tiredness was found from the mid-1990s to the end of the 2000s. The increase was evident in all participating age groups and in both genders. After 2008, the increase seems to have stopped. Insomnia symptoms and tiredness were associated with lower school performance and they were more prevalent among girls (11.9 and 18.4%) compared to boys (6.9 and 9.0%, respectively). Unexpectedly, we also observed an increasingly widening gap in school performance between normally vigilant and chronically tired pupils. The underlying causes of these phenomena are unknown, but may concern changes in the broader society. The observed recent increasing trend in adolescents' sleep problems is worrisome: poor sleep quality has also been suggested to associate with clinical or subclinical mood or anxiety disorders and behavioural problems and predispose to sleep and psychiatric disorders later in life. Our results justify further studies and call for serious attention to be paid to adolescent's sleep in the Finnish educational system and society at large.

[Chronobiological treatments of mood disorders]. / Mielialahäiriöiden aikabiologiset hoidot.

Chronobiological treatments are non-pharmacological treatments that influence the circadian rhythms and the physiology of sleep. In these treatments, the sleep-wake cycle and exposure to environmental stimuli affecting the biological rhythms are controlled. The aim is to produce a therapeutic effect in the treatment of psychiatric disorders. Chronobiological treatments include manipulations of the sleep-wake cycle, like sleep deprivation and advanced sleep-wake rhythm, and scheduled exposures to light and darkness. The clinical use of chronobiological treatments in Finland has been minimal and limited to the treatment of mood disorders, especially depressive disorders.

The relationship between mood and sleep in different female reproductive states.

BACKGROUND: Sleep is disrupted in depressed subjects, but it also deteriorates with age and possibly with the transition to menopause. The nature of interaction between mood, sleep, age and reproductive state is not well-defined. The aim of this study was to evaluate the relationship between mood and sleep among healthy women in different reproductive states. METHODS: We analyzed data from 11 younger (20-26 years), 21 perimenopausal (43-51 years) and 29 postmenopausal (58-71 years) healthy women who participated in a study on menopause, sleep and cognition. The 21-item Beck Depression Inventory (BDI) was administered to assess mood. Subjective sleep quality was assessed with the Basic Nordic Sleep Questionnaire (BNSQ). Objective sleep was measured with all-night polysomnography (PSG) recordings. Perimenopausal and younger women were examined during the first days of their menstrual cycle at the follicular phase. RESULTS: Among younger women, less arousals associated with higher BDI total scores (p = 0.026), and higher SWS percentages with more dissatisfaction (p = 0.001) and depressive-somatic symptoms (p = 0.025), but with less depressive-emotional symptoms (p = 0.001). In specific, less awakenings either from REM sleep or SWS, respectively, associated with more punishment (p = 0.005; p = 0.036), more dissatisfaction (p < 0.001; p = 0.001) and more depressive-somatic symptoms (p = 0.001; p = 0.009), but with less depressive-emotional symptoms (p = 0.002; p = 0.003). In perimenopausal women, higher BNSQ insomnia scores (p = 0.005), lower sleep efficiencies (p = 0.022) and shorter total sleep times (p = 0.024) associated with higher BDI scores, longer sleep latencies with more depressive-somatic symptoms (p = 0.032) and longer REM latencies with more dissatisfaction (p = 0.017). In postmenopausal women, higher REM percentages associated with higher BDI total scores (p = 0.019) and more depressive-somatic symptoms (p = 0.005), and longer SWS latencies with more depressive-somatic symptoms (p = 0.030). CONCLUSIONS: Depressive symptoms measured with the total BDI scores associated with sleep impairment in both perimenopausal and postmenopausal women. In younger women, specific BDI factors revealed minor associations, suggesting that the type of sleep impairment can vary in relation to different depressive features. Our data indicate that associations between sleep and depressed mood may change in conjunction with hormonal milestones.

Sleep in conduct-disordered adolescents--a polysomnographic and spectral power analysis study.

The aim of the present study was to characterize sleep in conduct-disordered adolescents using polysomnography and spectral power analysis. The two hypotheses were that conduct disorder would be associated with objective sleep problems, and that conduct disorder--as a precursor of adult antisocial personality disorder--would be associated with the same kind of abnormal sleep architecture, with both increased deep sleep and delta power, as previously reported in antisocial personality disorder. The patients consisted of 15 adolescents (age range 13-17 years, mean age 14.7 years) with histories of antisocial behavior so functionally impairing that they were ordered by child welfare to undergo a psychosocial evaluation in a closed social services ward. The healthy age-matched controls comprised 20 volunteers recruited with a newspaper advertisement. Opposite to earlier subjective sleep studies among conduct-disordered children, no significant differences in sleep parameters were observed between the two groups. The adolescents with conduct disorder slept a little bit longer, but the percentage amount of different sleep stages did not differ significantly between the two groups. Relative spectral power of sleep, delta power in particular, was similar in both groups, assessed in total sleep time as well as in first half of it. Different alternative explanations for these findings are discussed.

Sleep architecture in homicidal women with antisocial personality disorder--a preliminary study.

The aim of the present study was to characterize sleep in severely violent women with antisocial personality disorder (ASP) as the primary diagnosis. Participants for this preliminary study were three drug-free female offenders ordered to undergo a forensic mental examination in a maximum security state mental hospital after committing homicide or attempted homicide. Ten healthy age- and gender-matched controls consisted of hospital staff with no history of physical violence. The most striking finding was the increased amount of slow wave sleep, particularly the deepest sleep stage, S4, in women with ASP. This finding is in agreement with previously reported results in habitually violent male criminals with ASP. Severe female aggression seems to be associated with profound changes in sleep architecture. Whether this reflects specific brain pathology, or a delay in the normal development of sleep patterns in the course of aging, needs to be clarified. From the perspective of sleep research, the biological correlates of severe impulsive violence seem to be similar in both sexes.

Hormone treatment gives no benefit against cognitive changes caused by acute sleep deprivation in postmenopausal women.

The objective was to evaluate whether hormone therapy (HT) gives any benefit against the possible impairment of cognitive performance when challenged by acute sleep deprivation. Twenty postmenopausal women volunteered (age range 59-72 years, mean=64.4 years, SD=4.4): 10 HT users and 10 nonusers. Eleven young women served as a control group for the cognitive age effect (age range 20-26 years, mean age 23.1 years, SD=1.6). The subjects spent four consecutive nights at the sleep laboratory and were exposed to acute sleep deprivation of 40 h. Measures of attention (reaction speed and vigilance), alertness, and mood were administered every 2 h during the daytime and every hour during the sleep deprivation night. Postmenopausal women performed slower than young controls, whereas young controls made more errors. In HT users, the recovery night did not fully restore the performance in the simple and two-choice reaction time tasks, but in nonusers it did so. Sleep deprivation had a detrimental, yet reversible effect on vigilance in all groups. In all groups, sleepiness started to increase after 15 h of sleep deprivation and remained elevated in the morning after the recovery night. Prolonged wakefulness or HT had no effect on mood. In conclusion, sleep deprivation impaired cognitive performance in postmenopausal as well as young women. Postmenopausal women kept up their performance at the expense of reaction speed and young women at the expense of accuracy. One night was not enough for HT users to recover from sleep deprivation. Thus, HT gave no benefit in maintaining the attention and alertness during sleep deprivation.

Local energy depletion in the basal forebrain increases sleep.

Sleep saves energy, but can brain energy depletion induce sleep? We used 2,4-dinitrophenol (DNP), a molecule which prevents the synthesis of ATP, to induce local energy depletion in the basal forebrain of rats. Three-hour DNP infusions induced elevations in extracellular concentrations of lactate, pyruvate and adenosine, as well as increases in non-REM sleep during the following night. Sleep was not affected when DNP was administered to adjacent brain areas, although the metabolic changes were similar. The amount and the timing of the increase in non-REM sleep, as well as in the concentrations of lactate, pyruvate and adenosine with 0.5-1.0 mM DNP infusion, were comparable to those induced by 3 h of sleep deprivation. Here we show that energy depletion in localized brain areas can generate sleep. The energy depletion model of sleep induction could be applied to in vitro research into the cellular mechanisms of prolonged wakefulness.