Dysregulated sleep-wake cycles in young people are associated with emerging stages of major mental disorders.

AIM: To determine if disturbed sleep-wake cycle patterns in young people with evolving mental disorder are associated with stages of illness. METHODS: The sleep-wake cycle was monitored using actigraphy across 4 to 22 days. Participants (21 healthy controls and 154 persons seeking help for mental health problems) were aged between 12 and 30 years. Those persons seeking mental health care were categorized as having mild symptoms (stage 1a), an 'attenuated syndrome' (stage 1b) or an 'established mental disorder' (stage 2+). RESULTS: The proportions of individuals with a delayed weekdays sleep schedule increased progressively across illness stages: 9.5% of controls, 11.1% of stage 1a, 25.6% of stage 1b, and 50.0% of stage 2+ (χ(2) (3 d.f.) = 18.4, P < 0.001). A similar pattern was found for weekends (χ(2) (3 d.f.) = 7.6, P = 0.048). Compared with controls, stage 1b participants had later sleep onset on weekends (P = 0.015), and participants at stages 1b and 2+ had later sleep offset on both weekdays and weekends (P < 0.020). Compared with controls, all participants with mental disorders had more wake after sleep onset (P < 0.029) and those at stages 1a and 2+ had lower sleep efficiency (P < 0.040). Older age, medicated status and later weekdays sleep offset were found to be the three strongest correlates of later versus earlier clinical stages. CONCLUSIONS: In relation to clinical staging of common mental disorders in young people, the extent of delayed sleep phase is associated with more severe or persistent phases of illness.

Ambulatory sleep-wake patterns and variability in young people with emerging mental disorders.

BACKGROUND: The nature of sleep-wake abnormalities in individuals with mental disorders remains unclear. The present study aimed to examine the differences in objective ambulatory measures of the sleep-wake and activity cycles across young people with anxiety, mood or psychotic disorders. METHODS: Participants underwent several days of actigraphy monitoring. We divided participants into 5 groups (control, anxiety disorder, unipolar depression, bipolar disorder, psychotic disorder) according to primary diagnosis. RESULTS: We enrolled 342 participants aged 12-35 years in our study: 41 healthy controls, 56 with anxiety disorder, 135 with unipolar depression, 80 with bipolar disorder and 30 with psychotic disorders. Compared with the control group, sleep onset tended to occur later in the anxiety, depression and bipolar groups; sleep offset occurred later in all primary diagnosis groups; the sleep period was longer in the anxiety, bipolar and psychosis groups; total sleep time was longer in the psychosis group; and sleep efficiency was lower in the depression group, with a similar tendency for the anxiety and bipolar groups. Sleep parameters were significantly more variable in patient subgroups than in controls. Cosinor analysis revealed delayed circadian activity profiles in the anxiety and bipolar groups and abnormal circadian curve in the psychosis group. LIMITATIONS: Although statistical analyses controlled for age, the sample included individuals from preadolescence to adulthood. Most participants from the primary diagnosis subgroups were taking psychotropic medications, and a large proportion had other comorbid mental disorders. CONCLUSION: Our findings suggest that delayed and disorganized sleep offset times are common in young patients with various mental disorders. However, other sleep-wake cycle disturbances appear to be more prominent in broad diagnostic categories.

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.

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.

Sleep disturbance relates to neuropsychological functioning in late-life depression.

BACKGROUND: Sleep-wake disturbance in older people is a risk factor for depression onset and recurrence. The aim of this study was to determine if objective sleep-wake disturbance in late-life depression relates to neuropsychological functioning. METHODS: Forty-four older patients with a lifetime history of major depression and 22 control participants underwent psychiatric, medical and neuropsychological assessments. Participants completed self-report sleep measures, sleep diaries and wore wrist actigraphy for two weeks. Outcome measures included sleep latency, the number and duration of nocturnal awakenings and the overall sleep efficiency. RESULTS: Patients with depression had a greater duration of nocturnal awakenings and poorer sleep efficiency, in comparison to control participants. Sleep disturbance in patients was associated with greater depression severity and later ages of depression onset. It also related to poorer psychomotor speed, poorer verbal and visual learning, poorer semantic fluency as well as poorer performance on tests of executive functioning. These relationships largely remained significant after controlling for depression and estimated apnoea severity. LIMITATIONS: This sample had only mild levels of depression severity and results require replication in patients with moderate to severe depression. The inclusion of polysomnography and circadian markers would be useful to delineate the specific features of sleep-wake disturbance that are critical to cognitive performance. CONCLUSIONS: Sleep-wake disturbance in older patients with depression is related to neuropsychological functioning and to later ages of illness onset. This study suggests that common neurobiological changes may underpin these disease features, which may, in turn, warrant early identification and management.

Using the Internet to recruit patients for epilepsy trials: results of a New Zealand pilot study.

PURPOSE: We created a database that could be accessed via the Internet by any neurologist or pediatric neurologist in New Zealand. The database was designed to facilitate recruitment of patients for investigator-driven drug trials. METHODS: We established an epilepsy database, and invited neurologists and pediatric neurologists throughout New Zealand to register patients via the Internet when they were uncertain of the optimal management. Details regarding seizure type and frequency, epilepsy syndrome, etiology, drug history, and investigations were collected. We produced an algorithm to select patients who had failed to respond to a single antiepileptic drug (AED). These patients were randomized immediately via the Internet to receive a different drug. Participants were not reimbursed. RESULTS: The pilot study recruited patients from mid-June to December 2007. Sixteen neurologists participated; neurologists were based in eight different cities. One hundred thirty-seven patients were registered, of whom 113 were considered suitable for drug trials. Thirty-five patients who had used a single antiepileptic drug AED were enrolled, and 14 of these were successfully randomized online to a different drug. Follow-up information was entered via the Internet for all 108 patients who were seen again during the following year. DISCUSSION: We have demonstrated that patients can be recruited for trials and randomized from routine clinics via the Internet. Trials could compare AEDs or look at other aspects of epilepsy management. An international pilot study is planned. Neurologists are invited to enroll patients with epilepsy, who would be suitable for randomized controlled trials, into a Web-based register.