David B. Jarrett

Circadian rhythms in human performance and mood under constant conditions

This study explored the relationship between circadian performance rhythms and rhythms in rectal temperature, plasma cortisol, plasma melatonin, subjective alertness and well‐being. Seventeen healthy young adults were studied under 36 h of «unmasking» conditions (constant wakeful bedrest, temporal isolation, homogenized «meals») during which rectal temperatures were measured every minute, and plasma cortisol and plasma melatonin measured every 20 min. Hourly subjective ratings of global vigour (alertness) and affect (well‐being) were obtained followed by one of two performance batteries. On odd‐numbered hours performance (speed and accuracy) of serial search, verbal reasoning and manual dexterity tasks was assessed. On even‐numbered hours, performance (% hits, response speed) was measured at a 25–30 min visual vigilance task. Performance of all tasks (except search accuracy) showed a significant time of day variation usually with a nocturnal trough close to the trough in rectal temperature. Performance rhythms appeared not to reliably differ with working memory load. Within subjects, predominantly positive correlations emerged between good performance and higher temperatures and better subjective alertness; predominantly negative correlations between good performance and higher plasma levels of cortisol and melatonin. Temperature and cortisol rhythms correlated with slightly more performance measures (5/7) than did melatonin rhythms (4/7). Global vigour correlated about as well with performance (5/7) as did temperature, and considerably better than global affect (1/7). In conclusion: (1) between‐task heterogeneity in circadian performance rhythms appeared to be absent when the sleep/wake cycle was suspended; (2) temperature (positively), cortisol and melatonin (negatively) appeared equally good as circadian correlates of performance, and (3) subjective alertness correlated with performance rhythms as well as (but not better than) body temperature, suggesting that performance rhythms were not directly mediated by rhythms in subjective alertness.

Sleep, gender, and depression: An analysis of gender effects on the electroencephalographic sleep of 302 depressed outpatients

Gender-related differences in electroencephalographic (EEG) sleep were examined in 151 pairs of men and women with major depression, all outpatients, matched for age and severity of depression. Across five decades (age 21-69), depressed men had less slow-wave sleep than did depressed women. Gender differences were small with respect to visually scored measures of slow-wave sleep time and percent, but moderate for gender differences in automated measures of slow-wave density. The time constant of the polygraph preamplifier significantly affected both visually scored and automatically scored slow-wave sleep. Other measures such as REM sleep latency, first REM period duration, sleep efficiency, and early morning awakening, showed robust age effects, but no main effects for gender or gender-by-age interactions. Gender effects on slow-wave sleep and delta-wave counts in depression parallel gender effects seen in healthy aging. The possibility of occult alcohol use by depressed male outpatients cannot be definitely excluded as a partial explanation of the current findings. However, covarying for past alcohol abuse did not negate the statistical significance of the observed gender effects on slow-wave sleep and delta-wave density. The possibility of gender differences in slow-wave regulatory mechanisms is suggested, but similarity in temporal distribution of delta-wave density between the first and second non-rapid-eye-movement (NREM) periods does not support gender differences in slow-wave sleep regulation.

Application of automated REM and slow wave sleep analysis: II. Testing the assumptions of the two-process model of sleep regulation in normal and depressed subjects

Abnormalities in a two-process model of sleep regulation (a sleep-dependent process, termed Process S, and a sleep-independent circadian process, termed Process C) have been proposed to account for sleep abnormalities in depressive states. The major tenets of the two-process model of sleep regulation as applied to depression are: the level of process S, as reflected by the electroencephalographic (EEG) slow-wave activity, corresponds to the sleep-dependent facet of sleep propensity; the pathognomonic changes of sleep in depressives are a consequence of a deficiency in the build-up of process S. The application of automated rapid eye movement (REM) and delta wave analyses in normal subjects and younger depressed patients supports the model to some extent: The time spent asleep is positively correlated with total delta waves (normals and depressives) and average delta waves (depressives); delta sleep is lower in depressives than in normals; the average delta wave count is significantly reduced in younger depressives over the total night and in non-REM period 1. The model also postulates that measures of phasic REM activity are inversely related to process S, suggesting that process S can be regarded as exerting an inhibitory influence on phasic REM activity.

Application of automated REM and slow wave sleep analysis: I. Normal and depressed subjects.

Computerized analysis of rapid eye movement (REM) and delta electroencephalographic (EEG) sleep patterns in normal and depressed subjects offers opportunities to examine sleep more precisely than previously possible. In the present study, automated REM analyses demonstrated good reliability with traditional manual procedures in both normal and depressed subjects. However, automated delta analyses correlated well with traditional scoring in normal subjects, but not in depressed patients. These findings suggest the use of automated delta techniques similar to those employed in this report or spectral analytic techniques in the following types of studies: specificity of delta sleep in various psychiatric syndromes, changes in delta sleep produced by the administration of psychotropic agents, relationships between delta sleep and sleep-related neuro-endocrine patterns, and, finally, relationships between delta sleep patterns and other biological rhythms such as activity and temperature.

A reexamination of the relationship between growth hormone secretion and slow wave sleep using delta wave analysis

Sleep onset growth hormone secretion is a reliable and reproducible finding in young adults and children. Secretion typically occurs during the first non-REM period of sleep and, despite some evidence to the contrary, growth hormone secretion has frequently been associated with the first period of slow wave sleep. By measuring delta wave activity (0.5-2 Hz) instead of slow wave sleep and, accounting for the within subject variability, it has not been possible to demonstrate a consistent or statistically significant linear relationship between delta wave activity and sleep-related growth hormone secretion. This suggests the presence of more complex mediating factors and the possibility that sleep onset and growth hormone secretion are two separate processes which are independently stimulated by events associated with sleep onset.

Nighttime plasma cortisol secretion and EEG sleep--are they associated?

Since the initial rise in plasma cortisol during sleep usually occurs near the second period of rapid eye movement (REM) sleep, a more precise association between the initial cortisol rise and electroencephalographic (EEG) sleep was examined in 22 normal control subjects. Our results indicate that the length of the total non-REM sleep period between the first and second REM period including awake time was significantly correlated to the cortisol rise time. However, the timing of the initial cortisol rise was not significantly related to the overall plasma cortisol levels during the night. But the second non-REM sleep period (minus awake time) is inversely related to overall cortisol levels during the night.

Minute-by-minute analysis of REM sleep timing in major depression

Sleep changes described in depressed patients may represent alterations in the timing of rapid-eye-movement (REM) sleep or sleep onset. We examined these variables in groups of healthy control subjects (n = 47), depressed outpatients (n = 98), and depressed inpatients (n = 41). Outpatient depressives had greater severity of clinical symptoms than inpatients using the Hamilton Rating Scale for Depression. The depressed inpatient group had a later mean sleep onset time than the other groups, and the depressed outpatient group had a wider range of good night times than control subjects. REM timing in each group was examined as a relative frequency distribution of REM sleep (FDRS) for each minute across the night. The FDRSs for the three groups were statistically compared using the parameters from a two-component model, which includes a deterministic sinusoidal function and a time series process for errors. The slope of the linear trend in the FDRS rhythm was smaller (less positive) for both depressed groups than for controls. The ultradian FDRS rhythm occurred at an earlier phase, relative to sleep onset, in the inpatient depressed group compared to the control group. The ultradian FDRS rhythm had a longer period in the outpatient group compared to the control and inpatient groups. When referenced to 24-hr clock time in an exploratory analysis, the depressed groups appeared to have less robust FDRS ultradian rhythms than controls, but they did not appear to have a systematic phase alteration compared to controls. Abnormalities of REM sleep timing in groups of depressed patients may reflect a disturbance of sleep initiation and generation, or difficulty in entrainment of REM, rather than a systematic phase alteration in REM sleep propensity.

The effect of SRIF on the EEG sleep of normal men.

The aim of this investigation was to evaluate EEG sleep, especially measures of delta-wave sleep, during and after the administration of somatostatin (SRIF). Eleven normal men, ages 22-37 yr, were administered saline or SRIF (0.1 microgram/kg/min IV) over 160 min at bedtime. SRIF delayed sleep-related growth hormone (GH) secretion without altering the amount of GH available during the entire night of sleep. No changes in delta-wave sleep occurred during either the first 100 min of sleep or the remainder of the night. Furthermore, all major EEG sleep variables were not significantly different between the saline and SRIF infusion night. It would not appear that the peripheral administration of this dose of SRIF or the subsequent delay of GH release has quantitative effects on EEG measures of all-night sleep.

SLEEP-RELATED GROWTH HORMONE SECRETION IS PERSISTENTLY SUPPRESSED IN WOMEN WITH RECURRENT DEPRESSION : A PRELIMINARY LONGITUDINAL ANALYSIS

Growth hormone secretion was monitored during sleep in a group of 43 women with recurrent major depression who were participating in a 3-year maintenance therapy program. Patients were studied before acute treatment, after complete remission, and at 3-month intervals during maintenance treatment and the data generated were compared to those obtained in a control group of 14 age-matched healthy women studied once under identical conditions. When compared to the control group, the depressed patients secreted significantly less growth hormone before treatment. This reduction in growth hormone secretion, which was confined to the first half of the sleep period, persisted across the length of the maintenance study regardless of whether the subjects completed three years of therapy or experienced a recurrence.

Prolactin secretion during sleep: A comparison between depressed patients and healthy control subjects ☆

Although several neuroendocrine abnormalities have been described in depressed patients, relatively little attention has been paid to the pattern of prolactin secretion during sleep. Sleep disturbances are frequently found in depressed patients, and the sleep electroencephalogram (EEG) typically shows significant changes in the first and last 100 min, when prolactin secretion frequently occurs. In this study, carefully defined inclusion criteria were used to ensure comparability in the quality of the sleep maintenance, so that the pattern of sleep-related prolactin secretion in a group of 26 depressed inpatients could be compared to that in a group of 20 healthy control subjects. Starting from sleep onset, the patients did not show any statistically significant difference in either the serum prolactin concentration or the pattern of integrated prolactin secretion relative to the control subjects. A statistically significant relationship between prolactin secretion and the REM-non-REM sleep cycle could not be demonstrated in these subjects.