Rébecca Robillard

Delayed sleep phase in young people with unipolar or bipolar affective disorders

BACKGROUND Circadian disturbances may play a key role in the pathogenesis of some forms of mood disorders. Despite marked changes in circadian rhythms during the normal course of adolescence and young adulthood, less is known about changes in the 24-h sleep-wake cycle in young persons with mood disorders. METHODS Seventy-five young participants with mood disorders (unipolar: n=46, 20.1 ± 4.7 years old; bipolar I or II: n=29, 23.2 ± 4.3) and 20 healthy participants (24.8 ± 2.5 years old) underwent actigraphy monitoring during a depressive phase over seven consecutive days and nights. Sleep phase delay was defined as mean sleep onset ≥ 1:30 am and/or sleep offset ≥ 1 0:00 am. RESULTS A delayed sleep phase was found in 62% of participants with bipolar disorders when depressed, compared with 30% of those with unipolar depression (χ(2)=6.0, p=0.014) and 10% of control participants (χ(2)=11.2, p<0.001). Sleep offset times were significantly later in subjects with mood disorders compared to the control group, and later in those with bipolar as compared with unipolar disorders (all p ≤ 0.043). LIMITATIONS This study was cross-sectional and the depressed groups were somewhat younger compared to the healthy controls. Longitudinal studies are required to determine the predictive significance of these findings. CONCLUSIONS Young patients with mood disorders, especially those with bipolar disorders, are particularly likely to have a delayed sleep phase. Therapies focused on advancing sleep phase may be of specific benefit to these young persons.

Topography of age-related changes in sleep spindles.

Aging induces multiple changes to sleep spindles, which may hinder their alleged functional role in memory and sleep protection mechanisms. Brain aging in specific cortical regions could affect the neural networks underlying spindle generation, yet the topography of these age-related changes is currently unknown. In the present study, we analyzed spindle characteristics in 114 healthy volunteers aged between 20 and 73 years over 5 anteroposterior electroencephalography scalp derivations. Spindle density, amplitude, and duration were higher in young subjects than in middle-aged and elderly subjects in all derivations, but the topography of age effects differed drastically. Age-related decline in density and amplitude was more prominent in anterior derivations, whereas duration showed a posterior prominence. Age groups did not differ in all-night spindle frequency for any derivation. These results show that age-related changes in sleep spindles follow distinct topographical patterns that are specific to each spindle characteristic. This topographical specificity may provide a useful biomarker to localize age-sensitive changes in underlying neural systems during normal and pathological aging.

Sleep slow wave changes during the middle years of life

Slow waves (SW; < 4 Hz and > 75 μV) during non‐rapid eye movement (NREM) sleep in humans are characterized by hyperpolarization [surface electroencephalogram (EEG) SW negative phase], during which cortical neurons are silent, and depolarization (surface EEG positive phase), during which the cortical neurons fire intensively. We assessed the effects of age, sex and topography on the dynamics of SW characteristics in a large population (n = 87) of healthy young (23.3 ± 2.4 years) and middle‐aged (51.9 ± 4.6 years) volunteers. Older subjects showed lower SW density and amplitude than young subjects. Age‐related lower SW density in men was especially marked in prefrontal/frontal brain areas, where they originate more frequently. Older subjects also showed longer SW positive and negative phase durations. These last results indicate that, in young subjects, cortical neurons would synchronously enter the SW hyperpolarization and depolarization phases, whereas this process would take longer in older subjects, leading to lower slope and longer SW positive and negative phases. Importantly, after controlling for SW amplitude, middle‐aged subjects still showed lower slope than young subjects in prefrontal, frontal, parietal and occipital derivations. Age‐related effects on SW density, frequency and positive phase duration were more prominent at the beginning of the night, when homeostatic sleep pressure is at its highest. Age‐related SW changes may be associated with changes in synaptic density and white matter integrity and may underlie greater sleep fragmentation and difficulty in recuperating and maintaining sleep under challenges in older subjects.

Challenging sleep in aging: the effects of 200 mg of caffeine during the evening in young and middle-aged moderate caffeine consumers

The aim of this study was to evaluate the effects of a 200‐mg administration of caffeine on polysomnographic sleep variables and quantitative sleep electroencephalography (EEG) in 12 young (20–30 years) and 12 middle‐aged (40–60 years) moderate caffeine consumers (one to three cups of coffee per day). All subjects were submitted to both a caffeine (200 mg) and placebo (lactose) condition in a double‐blind cross‐over design. The conditions were separated by 1 week. Compared with the placebo condition, the evening ingestion of caffeine lengthened sleep latency, reduced sleep efficiency, and decreased sleep duration and amount of stage 2 sleep in both age groups. Caffeine also reduced spectral power in delta frequencies in frontal, central and parietal brain areas, but not in prefrontal (PF) and occipital regions. Moreover, caffeine increased spectral power in beta frequencies in frontal and central brain areas in both age groups. A suppression of spectral power in the PF area in low delta frequencies (0.5–1.00 Hz) and a rise in spectral power in the parietal region in high alpha (10.00–12.00 Hz) and beta frequencies (17.00–21.00, 23.00–25.00, 27.00–29.00 Hz) occurred solely in middle‐aged subjects. No such changes were noticeable in young subjects. Generally, caffeine produced similar effects in young and middle‐aged subjects. Only a few frequency bins showed more effects of caffeine in middle‐aged subjects compared with young subjects. Furthermore, sleep EEG results do not entirely support the hypothesis that caffeine fully mimics the effects of a reduction of homeostatic sleep propensity when following a normal sleep–wake cycle.

Sleep-wake cycle and melatonin rhythms in adolescents and young adults with mood disorders: Comparison of unipolar and bipolar phenotypes

This study evaluated the potential of circadian measures as early markers of mood disorders subtypes. Patients with bipolar disorders had significantly lower levels and later onset of melatonin secretion than those with unipolar depression. Furthermore, abnormal phase angles between sleep, melatonin and temperature were found in several patients.

Effects of Caffeine are more Marked on Daytime Recovery Sleep than on Nocturnal Sleep

Caffeine is often used to counteract sleepiness generated by sleep deprivation, jet lag, and shift-work, and is consumed at different times of day. Caffeine also has effects on sleep. However, little is known about the interaction between sleep deprivation, circadian timing, and caffeine consumption on sleep. In this study, we compared the effects of caffeine on nocturnal sleep initiated at habitual circadian time and on daytime recovery sleep. Thirty-four moderate caffeine consumers participated in both caffeine (200 mg) and placebo (lactose) conditions in a double-blind crossover design. Seventeen subjects followed their habitual sleep–wake cycle and slept in the laboratory during the night (Night), while 17 subjects were sleep deprived for one night and recovery sleep started in the morning (DayRec). All subjects received a capsule of 100 mg of caffeine (or placebo) 3 h before bedtime, and the remaining dose 1 h before bedtime. Compared to placebo, caffeine lengthened sleep latency, increased stage 1, and reduced stage 2 and slow-wave sleep (SWS) in both groups. However, caffeine reduced sleep efficiency more strongly in the DayRec group, and decreased sleep duration and REM sleep only in that group. The stronger effects of caffeine on daytime recovery sleep compared to nocturnal sleep are probably the consequence of the combined influence of increasing circadian wake propensity drive and the dissipation of homeostatic sleep pressure. We propose that the reduction of SWS by caffeine during daytime sleep increases the impact of the circadian wake signal on sleep. These results have implications for individuals using caffeine during night time.

Manipulating the sleep-wake cycle and circadian rhythms to improve clinical management of major depression

BackgroundClinical psychiatry has always been limited by the lack of objective tests to substantiate diagnoses and a lack of specific treatments that target underlying pathophysiology. One area in which these twin failures has been most frustrating is major depression. Due to very considerable progress in the basic and clinical neurosciences of sleep-wake cycles and underlying circadian systems this situation is now rapidly changing.DiscussionThe development of specific behavioral or pharmacological strategies that target these basic regulatory systems is driving renewed clinical interest. Here, we explore the extent to which objective tests of sleep-wake cycles and circadian function - namely, those that measure timing or synchrony of circadian-dependent physiology as well as daytime activity and nighttime sleep patterns - can be used to identify a sub-class of patients with major depression who have disturbed circadian profiles.SummaryOnce this unique pathophysiology is characterized, a highly personalized treatment plan can be proposed and monitored. New treatments will now be designed and old treatments re-evaluated on the basis of their effects on objective measures of sleep-wake cycles, circadian rhythms and related metabolic systems.

Sleep-wake cycle in young and older persons with a lifetime history of mood disorders.

Considering the marked changes in sleep and circadian rhythms across the lifespan, age may contribute to the heterogeneity in sleep-wake profiles linked to mood disorders. This study aimed to investigate the contributions of age and depression severity to sleep-wake disturbances. The Hamilton Depression Rating Scale (HDRS) was administered to assess current symptoms severity in 238 persons with a history of a mood disorder between 12 and 90 years of age (y.o.). Actigraphy was recorded over five to 22 days. Regression analyses and analyses of variance [age (12–19 y.o., 20–39 y.o., 40–59 y.o., and ≥60 y.o.) by depression severity (HDRS< and ≥8)] were conducted. The 12–19 y.o. and 20–39 y.o. groups had a delayed sleep schedule and acrophase compared to all other groups. The ≥60 y.o. group had a lower rhythmicity and amplitude (p≤.006) than the 12–19 y.o. group (p≤.046). Participants with a HDRS≥8 spent longer time in bed, had later sleep offset times and had lower circadian rhythmicity than those with a HDRS<8 (p≤.036). Younger age and higher HDRS score correlated with later sleep onset and offset times, longer time in bed, higher WASO, lower sleep efficiency and later acrophase (p≤.023). Age was a significant predictor of delayed sleep and activity schedules (p≤.001). The profile of sleep-wake cycle disturbances associated with mood disorders changes with age, with prominent sleep phase delay during youth and reduced circadian strength in older persons. Conversely, disruptions in sleep consolidation seem more stable across age.

Neuropsychological and Functional Outcomes in Recent-Onset Major Depression, Bipolar Disorder and Schizophrenia-Spectrum Disorders: A Longitudinal Cohort Study.

Functional disability is the lead contributor to burden of mental illness. Cognitive deficits frequently limit functional recovery, although whether changes in cognition and disability are longitudinally associated in recent-onset individuals remains unclear. Using a prospective, cohort design, 311 patients were recruited and assessed at baseline. One hundred and sixty-seven patients met eligibility criteria (M=21.5 years old, s.d.=4.8) and returned for follow-up (M=20.6 months later, s.d.=7.8). Two-hundred and thirty participants were included in the final analysis, comprising clinically stable patients with major depression (n=71), bipolar disorder (BD; n=61), schizophrenia-spectrum disorders (n=35) and 63 healthy controls. Neuropsychological functioning and self-rated functional disability were examined using mixed-design, repeated-measures analysis, across diagnoses and cognitive clusters, covarying for relevant confounds. Clinical, neuropsychological and functional changes did not differ between diagnoses (all P>0.05). Three reliable neuropsychological subgroups emerged through cluster analysis, characterized by psychomotor slowing, improved sustained attention, and improved verbal memory. Controlling for diagnosis and changes in residual symptoms, clusters with improved neuropsychological functioning observed greater reductions in functional disability than the psychomotor slowing cluster, which instead demonstrated a worsening in disability (P<0.01). Improved sustained attention was independently associated with greater likelihood of follow-up employment (P<0.01). Diagnosis of BD uniquely predicted both follow-up employment and independent living. Neuropsychological course appears to be independently predictive of subjective and objective functional outcomes. Importantly, cognitive phenotypes may reflect distinct pathophysiologies shared across major psychiatric conditions, and be ideal targets for personalized early intervention.

Topography of homeostatic sleep pressure dissipation across the night in young and middle‐aged men and women

Decline in slow‐wave activity (SWA) across the night is believed to reflect dissipation of the homeostatic sleep drive. This study evaluated the effects of age, sex and topography on SWA dissipation. The sleep electroencephalogram of 48 young [22 women, 26 men; mean = 23.3 years; standard deviation (SD) = 2.4] and 39 middle‐aged (21 women, 18 men; mean = 51.9 years; SD = 4.6) healthy volunteers was analysed. Spectral analysis (0.5–22.0 Hz) was performed per non‐rapid eye movement period for Fp1, F3, C3, P3 and O1. SWA (1.0–5.0 Hz) dissipation was modelled using linear and exponential decay functions applied to each age and sex subgroup data set for each derivation. The relative adequacy of both functions was compared using Akaike’s information criterion. Results suggest that the exponential model provides a better data fit than the linear fit independently of age, gender and brain location. In women, age reduced the span (distance between the y intercept and the asymptote) of SWA decay in Fp1, F3, P3 and O1. In men, however, the effect of age on the span of SWA decay was limited to Fp1 and F3. In all age and sex subgroups, anterior regions showed a higher span than posterior regions. The asymptote was lower in anterior regions in young but not in middle‐aged subjects. These results suggest that the homeostatic process operates on a larger scale in anterior regions. Importantly, ageing reduced the scale of homeostatic dissipation in both sexes, but this effect was more widespread across the brain in women.