Irregular sleep habits, regional grey matter volumes, and psychological functioning in adolescents.

Changing sleep rhythms in adolescents often lead to sleep deficits and a delay in sleep timing between weekdays and weekends. The adolescent brain, and in particular the rapidly developing structures involved in emotional control, are vulnerable to external and internal factors. In our previous study in adolescents at age 14, we observed a strong relationship between weekend sleep schedules and regional medial prefrontal cortex grey matter volumes. Here, we aimed to assess whether this relationship remained in this group of adolescents of the general population at the age of 16 (n = 101; mean age 16.8 years; 55% girls). We further examined grey matter volumes in the hippocampi and the amygdalae, calculated with voxel-based morphometry. In addition, we investigated the relationships between sleep habits, assessed with self-reports, and regional grey matter volumes, and psychological functioning, assessed with the Strengths and Difficulties Questionnaire and tests on working memory and impulsivity. Later weekend wake-up times were associated with smaller grey matter volumes in the medial prefrontal cortex and the amygdalae, and greater weekend delays in wake-up time were associated with smaller grey matter volumes in the right hippocampus and amygdala. The medial prefrontal cortex region mediated the correlation between weekend wake up time and externalising symptoms. Paying attention to regular sleep habits during adolescence could act as a protective factor against the emergence of psychopathology via enabling favourable brain development.

Sleep symptoms and long-term outcome in adolescents with major depressive disorder: a naturalistic follow-up study.

Sleep abnormalities in major depressive disorder (MDD) have been suggested to represent a vulnerability trait, which might predispose the individual to long-term psychiatric morbidity. In this study, we sought to assess whether the presence of sleep symptoms among adolescents with MDD is associated with poorer long-term outcome in young adulthood during naturalistic follow-up. Adolescent outpatients diagnosed with MDD (n = 166; age 13-19 years, 17.5% boys) were followed up during 8 years in naturalistic settings. N = 112 adolescents (16.1% boys) completed the 8-year assessment. Sleep symptoms and psychosocial functioning were assessed with structured clinical interviews, and depressive and anxiety symptoms with questionnaires. The severity of sleep symptoms at baseline was not associated with worse outcome at 8 years in terms of any of the outcome measures tested. In particular, the presence of a disturbed sleep-wake rhythm at baseline was associated with a more favourable outcome at 8 years: less depression and anxiety symptoms and higher level of psychosocial functioning. The presence of sleep symptoms in young adulthood was associated with the presence of current depression and anxiety symptoms and poorer psychosocial functioning. The presence of sleep symptoms at follow-up seems to be state-dependent: they are observed in conjunction with other psychiatric symptoms. Contrary to our hypothesis, our results suggest that sleep complaints among adolescents with MDD do not lead to poorer long-term clinical outcome in young adulthood. The link between sleep-wake rhythm disturbance and better long-term outcome needs to be confirmed and examined in detail in further studies, but here we speculate about possible explanations.

First-Night Effect on Sleep in Different Female Reproductive States.

OBJECTIVES: In sleep laboratory studies, the new environment is generally considered to disturb sleep during the first night. However, older women have rarely been studied. Although menopause and hormone therapy affect sleep, their impact on the first-night effect is virtually unknown. PARTICIPANTS: Four groups of women with no sleep laboratory experience: young on hormonal contraceptives (n = 11, 23.1 [0.5] years), perimenopausal (n = 15, 48.0 [0.4] years), postmenopausal without hormone therapy (HT; off-HT, n = 22, 63.4 [0.8] years) and postmenopausal with HT (n = 16, 63.1 [0.9] years). PROCEDURE: A cross-sectional study. METHODS: Polysomnography was performed over two consecutive nights and the first-night effect and group differences were evaluated. Questionnaire-based insomnia and sleepiness scores were correlated to sleep variables and their between-night changes. RESULTS: Although sleep in young women was deeper and less fragmented than in the other groups, first-night effect was similar in all study groups. Total sleep time, sleep efficiency, and S1 and S2 sleep increased, and wake after sleep onset, awakenings per hour of sleep, S2 and REM latencies, and percentage of SWS decreased from the first to the second night. Perimenopausal women had more insomnia complaints than other women. Insomnia complaints were associated with more disturbed sleep but not with the first-night effect. CONCLUSIONS: A first night in a sleep laboratory elicits a marked interference of sleep architecture in women of all ages, with a carryover effect of lighter sleep on the second study night. Menopausal state, HT use, or insomnia complaints do not modify this effect.

First-night effect on cardiac autonomic function in different female reproductive states.

Decreases in heart rate variability, a marker of autonomic nervous system function, are associated with increased cardiovascular mortality. Heart rate variability increases in non-rapid eye movement sleep, peaking in slow-wave sleep. Therefore, decreasing the amount of deep sleep, for example, by introducing patients to a sleep laboratory environment, could decrease heart rate variability, increasing cardiovascular risk. We studied four groups of women with no previous sleep laboratory experience: young [n = 11, 23.1 (0.5) years]; perimenopausal [n = 15, 48.0 (0.4) years]; postmenopausal without hormone therapy [n = 22, 63.4 (0.8) years]; and postmenopausal on hormone therapy [n = 16, 63.1 (0.9) years], using a cross-sectional design. Polysomnography including electrocardiogram was performed over two consecutive nights. Heart rate variability was assessed overnight, and the first-night effect on heart rate variability was analysed. Furthermore, correlations between heart rate variability and sleep variables were analysed. Using combined groups, only minor changes were observed in non-linear heart rate variability, indicating increased parasympathetic tone from the first to the second night. No group differences in first-night effect were seen. Heart rate variability and sleep variables were not significantly correlated. Heart rate variability decreased with increasing age, and it was lowest in the postmenopausal women on hormone therapy. We conclude that a first night in a sleep laboratory elicits only minimal changes in overnight vagally mediated non-linear heart rate variability in women irrespective of reproductive state. This finding warrants further analyses in different sleep stages, but suggests that changes in sleep architecture per se do not predict the autonomic strain of a poor night.

Sleep and slow-wave activity in depressed adolescent boys: a preliminary study.

OBJECTIVE: Adolescence is a vulnerable period of life that is characterized by increasing incidence of depression. Sleep disturbance is one of the diagnostic symptoms of depressive disorder. Adolescence is also characterized by dramatic maturational changes in sleep and its regulation. The goal of this study was to assess sleep macroarchitecture and slow-wave activity (SWA) in depressed adolescent boys. METHODS: Eight non-medicated adolescent boys meeting the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for depressive disorder and 10 age-matched healthy controls (average age 16.0 years) underwent polysomnography in their home environment for two consecutive nights. Sleep macroarchitecture, SWA, and SWA dissipation were assessed in all subjects. RESULTS: Depressed boys showed a flattened pattern of SWA dissipation through the night. SWA power was lower during the first non-rapid eye movement (NREM) episode in the frontal derivation and higher during the third NREM episode in the central derivation in the group of depressed boys as compared to healthy boys. The SWA dissipation pattern correlated with the severity of depressive symptoms, and the correlation was strongest in the frontal derivation. In addition, total sleep time was shorter in patients as compared to the control group, but no other differences were found in the macroarchitecture of sleep. CONCLUSION: Depression in adolescent boys is characterized by more evenly distributed SWA through the night as compared to healthy subjects, and we showed for the first time that this pattern of SWA distribution is associated with severity of depressive symptoms. These findings suggest that homeostatic regulation of sleep may be impaired in adolescent depression.

Frontal Cortex Myo-Inositol Is Associated with Sleep and Depression in Adolescents: A Proton Magnetic Resonance Spectroscopy Study.

AIM: This study used proton magnetic resonance spectroscopy (1H MRS) to evaluate the neurochemistry of the frontal cortex in adolescents with symptoms of sleep and depression. METHODS: Nineteen non-medicated adolescent boys (mean age 16.0 years; 9 clinical cases with depression/sleep symptoms and 10 healthy controls) underwent 1H MRS at 3 T. MR spectra were acquired from the anterior cingulate cortex (ACC), the dorsolateral prefrontal cortex, and frontal white matter. Concentrations of N-acetyl aspartate, total creatine, choline-containing compounds, total glutamine plus glutamate, and myo-inositol (mI) were compared in the 2 subgroups, and correlated with sleep and clinical measures in the total sample. Sleep was assessed with self-report questionnaires and ambulatory polysomnography recordings. RESULTS: Concentrations of mI were lower in both frontal cortical regions among the depressed adolescents than in controls. No statistically significant differences in other metabolite concentrations were observed between the subgroups. Frontal cortex mI concentrations correlated negatively with depression severity, subjective daytime sleepiness, insomnia symptoms, and the level of anxiety, and correlated positively with total sleep time and overall psychosocial functioning. The correlations between mI in the ACC and total sleep time as well as daytime sleepiness remained statistically significant when depression severity was controlled in the analyses. CONCLUSION: Lower frontal cortex mI may indicate a disturbed second messenger system. Frontal cortical mI may thus be linked to the pathophysiology of depression and concomitant sleep symptoms among maturing adolescents. Short sleep and daytime sleepiness may be associated with frontal cortex mI independently from depression.

Advanced phases and reduced amplitudes are suggested to characterize the daily rest-activity cycles in depressed adolescent boys.

Self-reported eveningness has been previously associated with depressed mood among adults and adolescents. Here, we study how circadian indicators based on actigraphic data differ between depressed and healthy adolescent boys. Our sample consisted of 17 medication-free adolescent boys, aged 14.5 to 17.5 years, of which eight had depressive disorder and were currently depressed and nine were healthy comparison participants. Psychiatric assessment was conducted by diagnostic interviews and complemented with observer-rating and self-rating scales. Actigraphic data were collected with wrist actigraphs for a minimum period of 25 consecutive days (range of 25 to 44 days). The behavioral trait of morningness-eveningness was measured with the 19-item Horne-Östberg Morningness-Eveningness Questionnaire. Based on the self-report, the depressed boys were more prone to eveningness than healthy controls, but based on the actigraphic data, they had earlier phases especially on school days and lower activity levels especially on weekends. On weekends, the depressed boys showed a greater shift toward later-timed phases than healthy controls. Our results confirm a mismatch of the subjective morningness-eveningness preference (late-preference) and the objective rest-activity rhythm (early-prone) during school days in depressed adolescent boys.

Sleep habits, academic performance, and the adolescent brain structure.

Here we report the first and most robust evidence about how sleep habits are associated with regional brain grey matter volumes and school grade average in early adolescence. Shorter time in bed during weekdays, and later weekend sleeping hours correlate with smaller brain grey matter volumes in frontal, anterior cingulate, and precuneus cortex regions. Poor school grade average associates with later weekend bedtime and smaller grey matter volumes in medial brain regions. The medial prefrontal - anterior cingulate cortex appears most tightly related to the adolescents' variations in sleep habits, as its volume correlates inversely with both weekend bedtime and wake up time, and also with poor school performance. These findings suggest that sleep habits, notably during the weekends, have an alarming link with both the structure of the adolescent brain and school performance, and thus highlight the need for informed interventions.

Cardiac autonomic changes after 40 hours of total sleep deprivation in women.

OBJECTIVES: The effect of total sleep deprivation on heart rate variability (HRV) in groups of postmenopausal women on oral hormone therapy (HT) (on-HT, n = 10, 64.2 (1.4) years), postmenopausal women without HT (off-HT, n = 10, 64.6 (1.4) years) and young women (n = 11, 23.1 (0.5) years) was studied using a prospective case-control setup. METHODS: Polysomnography was performed over an adaptation night, a baseline night, and a recovery night after 40 h of total sleep deprivation. Time and frequency domain and nonlinear HRV from overnight electrocardiogram recordings were compared between groups during baseline and recovery nights. Further, the changes in HRV from baseline to recovery were analysed and compared between groups. Finally, correlations of HRV to percentages of sleep stages and measures of sleep fragmentation were analysed during baseline and recovery. RESULTS: Young women had higher HRV than older women; the most marked difference was between young and on-HT postmenopausal women. Sleep deprivation induced a decrease in frequency domain HRV in young and in off-HT women, an increase in α2 in off-HT women, and an increase in mean heart rate in on-HT women. The sleep deprivation effect was mainly uncorrelated to changes in sleep parameters. CONCLUSIONS: Acute total sleep deprivation has a deleterious effect on the autonomic nervous system in young women, but an even more pronounced effect in postmenopausal women. Hormone therapy use in late postmenopause does not give protection against these changes. These harmful effects may partly explain the increased cardiovascular morbidity and overall mortality associated with sleep loss.

Sleep complaints in adolescent depression: one year naturalistic follow-up study.

BACKGROUND: Sleep complaints are highly prevalent in adolescents suffering from major depressive disorder (MDD). The aims of this study were to describe the longitudinal course of sleep complaints, and to assess the association between sleep complaints and clinical outcome in a sample of adolescents with MDD during naturalistic follow-up. METHODS: A sample of adolescent outpatients (n = 166; age 13-19 years, 17.5% boys) diagnosed with MDD was followed-up during one year in naturalistic settings. Sleep symptoms and psychiatric symptoms were assessed with interviews and self-report questionnaires. RESULTS: All sleep complaints were less frequent at one-year follow-up compared to baseline. Baseline sleep complaints did not adversely affect clinical outcome at one-year follow-up: severity of the sleep complaints at baseline was associated with a steeper improvement of depressive and anxiety symptoms, suicidality/self-harm symptoms, and overall psychosocial functioning over time. CONCLUSIONS: Our results suggest that sleep disturbances at baseline do not necessarily lead to poorer clinical outcome during follow-up. Larger longitudinal studies combining both subjective and objective measures of sleep in depressed adolescents are needed to clarify the link between sleep and depression further.

Sleep complaints among adolescent outpatients with major depressive disorder.

OBJECTIVE: The objective of our study was to examine the prevalence rates of different sleep complaints among adolescent outpatients with major depressive disorder (MDD). Further, we examined whether depressed adolescents with and without different sleep disturbances differ in terms of severity of depression, the presence of comorbid psychiatric disorders, and the symptom profile of depression. METHODS: A total of 166 Finnish adolescent psychiatric outpatients (age 13-19; mean 16.5 years old; 17.5% boys) diagnosed with unipolar MDD (as defined by DSM-IV criteria) were included in the study. Their sleep complaints were assessed with self-rating scales and clinical research interviews. RESULTS: The prevalence rate of subjective sleep complaints in adolescents with MDD was high: 83% of the adolescents experienced significantly disturbed sleep. The most common types of sleep complaints were nonrestorative sleep (69%) and insomnia (51%). The presence of sleep disturbances was associated with severity of depression: Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI) total sum scores were highest in adolescents with multiple sleep disturbances and lowest in adolescents with no sleep problems. Adolescents with multiple sleep disturbances differed most from adolescents with no or minor sleep disturbances in terms of thoughts about death, suicidal thoughts, and anhedonia. CONCLUSIONS: These findings suggest a close link between sleep disturbances and the severity of depression in adolescent outpatients with MDD. In particular, the link between sleep disturbances and thoughts about death and suicidal thoughts calls for attention to sleep problems among depressed adolescents in clinical settings.

Sleep and the menopause - do postmenopausal women experience worse sleep than premenopausal women?

OBJECTIVE: To examine the sleep characteristics in three cross-sectional populations: young, premenopausal and postmenopausal women, and the associations between sleep, menopause, mood and cognitive performance. STUDY DESIGN: Twenty-one premenopausal (45-51 years), 29 postmenopausal (59-71 years) and 11 young (20-26 years, using oral contraceptives) women were recruited. Polysomnography was used to measure objective sleep quality. Subjective sleep quality, sleepiness and mood were assessed using questionnaires. Cognitive performance was investigated by means of three attentional tests. RESULTS: Total sleep time in pre- and postmenopausal women was similar (404.9 and 384.7 minutes), but shorter than in young women (448.2 minutes, P = 0.030 and <0.003, respectively). Sleep efficiency followed the same pattern, being 84.3% in premenopausal (P = 0.027), 80.2% in postmenopausal (P < 0.003) and 93.4% in young women. Pre- and postmenopausal women had less slow wave sleep (duration or activity) and more wake time after sleep onset (duration or frequency). Insomnia complaints were more frequent after the menopause (P = 0.023). Sleepiness and mood scores were similar in all groups. Reaction speeds slowed with increasing age. After the menopause, better cognitive performance was associated with more rapid eye movement sleep. CONCLUSION: Objective sleep measures differed significantly between the young and postmenopausal groups. These differences may be more because of the physiology of ageing than the rapid changes across the menopause, since similar sleep characteristics were already present in the premenopausal women. The increase in sleep complaints after menopause was not associated with sleepiness or disturbances in objective sleep quality, mood or cognitive performance.

Psychomotor vigilance task performance during total sleep deprivation in young and postmenopausal women.

The objective of this study was to investigate the effects of age on women's performance in the psychomotor vigilance task (PVT) during total sleep deprivation (SD). A total of 46 healthy women volunteered. They belonged to two age groups: young (n=34; age range 19-30 years; 12 without, and 22 with oral contraceptives (OC); early phase of the menstrual cycle) and older (n=12; age range 60-68; postmenopausal; without hormone therapy). During a 40-h total SD, the subjects performed the PVT and the Stanford Sleepiness Scale (SSS) at 2-h intervals. At baseline, the reaction speed of the young women was faster as compared to the older women (Mann-Whitney U-test p<0.01). During SD, all the PVT measures as well as the SSS scores changed similarly in the two age groups, when the baseline performance difference in favour of the young women was taken into account (area under curve analyses, Mann-Whitney U-tests n.s.). No age difference in the time course of the SD-related deterioration in PVT performance or subjective sleepiness was observed. OC use had no effects on any of the measures during SD. After recovery sleep, young women had higher subjective sleepiness scores than older women, the sleepiness scores being highest in young women not taking OCs. In conclusion, in women, aging has no effects on the amount or the time course of the decline in PVT performance caused by total SD. OC use does not significantly affect young women's PVT performance during SD in the early phase of the menstrual cycle.

Sleep deprivation and hormone therapy in postmenopausal women.

BACKGROUND AND PURPOSE: Sleep complaints increase after menopause, but literature on the effect of postmenopausal hormone therapy (HT) on sleep is controversial. The purpose of this study was to determine the effect of ageing and HT on sleep quality, assessed using polysomnography, and on the accuracy of the subjective estimation of sleep quality in women before and after sleep deprivation. PATIENTS AND METHODS: Twenty postmenopausal women (aged 58-72 years) were recruited: 10 HT-users and 10 non-HT-users. Eleven young women (aged 20-26 years) served as controls. Polysomnography and subjective sleep quality were measured on four consecutive nights: adaptation, baseline, 40-h sleep deprivation and recovery. RESULTS: Although the postmenopausal women slept worse than the controls at baseline, and in particular during the recovery night, their recovery response to sleep deprivation was well preserved. At baseline, HT-users had a shorter latency to rapid eye movement (REM) (P=0.043), with fewer awakenings from slow wave sleep (SWS) (P=0.029) but more from REM (P=0.033) than non-HT-users. During recovery, the HT-users had more stage 2 sleep (P=0.048) and less slow wave activity (SWA) in the first non-rapid eye movement (NREM) sleep episode (P=0.021) than the non-HT-users. The poor correlation between subjective and objective sleep quality at baseline became significant during recovery. CONCLUSIONS: Although sleep in postmenopausal women was worse than in young controls, the recovery response following sleep deprivation was relatively well preserved. HT offered no significant advantage to sleep at baseline and slightly weakened the recovery response to prolonged wakefulness.

Preliminary findings of proton magnetic resonance spectroscopy in occipital cortex during sleep deprivation.

Proton magnetic resonance spectroscopy ((1)H MRS) has revealed biochemical alterations in various psychiatric disorders. Changes in brain metabolites may be caused not only by the disease's progression or response to treatment, but also by physiological variability. The aim of this study was to use (1)H MRS to assess the effects of specific short-term physiological states on major metabolites. Eight healthy women underwent (1)H MRS at the beginning and end of a 40-h period of sleep deprivation. The ratios of N-acetyl-aspartate (NAA), total creatine (tCr), and choline-containing compounds (Cho) to water (H(2)O) were determined from the occipital cortex during both baseline and photic stimulation conditions. During sleep deprivation, NAA/H(2)O decreased by 7% and Cho/H(2)O by 12%. Photic stimulation had no effect on the measured metabolites in the alert state, but in the sleep-deprived state the level of Cho/H(2)O increased during neuronal activation. The results suggest that NAA/H(2)O and Cho/H(2)O may depend on the state of alertness.

Stimulus-induced brain lactate: effects of aging and prolonged wakefulness.

Both aging and sleep deprivation disturb the functions of the frontal lobes. Deficits in brain energy metabolism have been reported in these conditions. Neurons use not only glucose but also lactate as their energy substrate. The physiological response to elevated neuronal activity is a transient increase in lactate concentrations in the stimulated area. We have previously shown that cognitive stimulation increases brain lactate. To study the effect of prolonged wakefulness on the lactate response we designed an experiment to assess brain lactate levels during a 40-h sleep deprivation period in young (19-24 years old; n = 13) and in aged (60-68 years old; n = 12) healthy female volunteers. Brain lactate levels were assessed with proton MR-spectroscopy ((1)H MRS) during the performance of a silent word generation task. The (1)H MRS voxel location was individually selected, using functional magnetic resonance imaging, to cover the activated area in the left frontal lobe. The degree of sleepiness was verified using vigilance tests and self-rating scales. In the young alert subjects, the silent word generation test induced a 40% increase in lactate, but during the prolonged wakefulness period this response disappeared. In the aged subjects, the lactate response could not be detected even in the alert state. We propose that the absence of the lactate response may be a sign of malfunctioning of normal brain energy metabolism. The behavioral effects of prolonged wakefulness and aging may arise from this dysfunction.

Metabolic imaging of human cognition: an fMRI/1H-MRS study of brain lactate response to silent word generation.

Proton magnetic resonance spectroscopy (1H-MRS) allows in vivo assessment of the metabolism related to human brain functions. Visual, auditory, tactile, and motor stimuli induce a temporary increase in the brain lactate level, which may act as a rapid source of energy for the activated neurons. The authors studied the metabolism of the frontal lobes during cognitive stimulation and measured local lactate levels with standard 1H-MRS, after localizing the activated area by functional MRI. Lactate levels were monitored while the subjects either silently listed numbers (baseline) or performed a silent word-generation task (stimulus-activation). The cognitive stimulus-activation produced a 50% increase in the brain lactate level in the left inferior frontal gyrus. The results show that metabolic imaging of neuronal activity related to cognition is possible using 1H-MRS.