Sleep EEG recordings in generalized anxiety disorder with significant depression

After one accommodation night, sleep EEG recordings were performed during three consecutive nights in ten drug-free inpatients presenting generalized anxiety disorder (GAD) with significant depression, compared with a age- and sex-matched group of patients with GAD and a group of primary major depressive disorder (MDD) patients. GAD patients with depression did not differ from GAD patients in any sleep variable. Patients with MDD showed more stage shifts and a greater number of awakenings than patients with GAD. REM latency was significantly shorter in MDD patients than in the other groups, and may thus help to differentiate anxious from depressed patients.     

Delta sleep EEG in depressed adolescent females and healthy controls

BACKGROUND: Quantitative EEG studies have identified a number of sleep abnormalities in adults with major depressive disorders (MDD), including a reduction in the amplitude of delta activity during NREM sleep. To date, these methodologies have not been used in early onset MDD. METHODS: Delta activity during NREM sleep was compared in eight symptomatic but unmedicated adolescent females with MDD and eight age- and gender-matched healthy controls. RESULTS: The depressed group showed significantly lower delta amplitude and power in the first NREM sleep period. By contrast, standard sleep architecture did not differentiate between groups. LIMITATIONS: Given the sample size, this study is best viewed as tentative. In addition, it has yet to be determined whether adolescent males with MDD also show delta sleep abnormalities. Further, failure to find between-group differences in REM latency or other macroarchitectural measures may be due to the small sample size. CONCLUSIONS: The findings of this study underscore the utility of quantitative sleep EEG techniques in early onset MDD. The results of the present study do, however, diverge from reports in adults with MDD, where delta abnormalities are more prevalent in men. Such findings suggest that the maturational time course of sleep EEG disturbances may differ for males and females with depression. Early emergence of delta abnormalities in depression may be of relevance to clinical course of illness.     

The modifications of the long-range temporal correlations of the sleep EEG due to major depressive episode disappear with the status of remission

OBJECTIVE: The aim of the present study is to investigate the scaling properties of the sleep electroencephalogram (EEG) in remitted depressed men, and to evaluate if a past history of major depressive disorder (MDD) could modify significantly and definitively, as a "scar marker," the dynamics of the sleep EEG time series. METHODOLOGY: Whole night sleep electroencephalogram signals were recorded in 24 men: 10 untreated depressed men in full to partial remission (42.43+/-5.62 years) and 14 healthy subjects (42.8+/-8.55 years). Scaling properties in these time series were investigated with detrended fluctuation analysis (DFA) (time range: 0.16-2.00 s). The scaling exponent alpha was determined in stage 2, in slow wave sleep (stages 3 and 4), and during rapid eye movement (REM) sleep. Forty-five epochs of 20 s were chosen randomly in each of these stages for each subject in both groups. RESULTS: We did not observe a significant difference and deviation of the scaling exponents between the two groups during the three sleep stages of interest. CONCLUSION: In this study, we do not observe any functional sequelae of a past history of one or more unipolar major depressive episode on the fluctuation properties of the sleep EEG. This finding is a sign of similar underlying neuronal dynamics in healthy controls and patients with a lifetime history of MDD. This study gives an additional argument to the theory that depression does not modify definitively the dynamics of the neuronal networks and is therefore against the "depressive scar hypothesis," in which permanent residual deficit is created by the acute state of the depressive disease.     

EEG sleep of young adults with major depression: a controlled study

The EEG sleep of 75 subjects aged 16-25 years was studied. Thirty-eight were in an episode of RDC major depression, and 37 were normal controls. Only one sleep continuity measure differed between the two groups: sleep latency was significantly longer in the depressive group. REM period latencies and other sleep variables did not differ between the groups. Subgroup analyses, within the depressed group with respect to inpatient status, revealed significantly higher REM density (P less than 0.03) and a marginally shortened REM period latency (P less than 0.07) among the inpatient depressives. Subgroup analysis across suicidal ratings revealed a significantly higher REM density (P less than 0.04) among suicidal depressives. Severity estimates of depression did not correlate with sleep findings. These results parallel another recent report on adolescent depressed subjects, suggesting that inpatient and/or suicidal status is an important variable in the expression of EEG sleep abnormalities in the adolescent/young adult age group.     

Trimipramine: acute and lasting effects on sleep in healthy and major depressive subjects.

The acute effects of trimipramine on sleep EEG patterns were investigated in six depressed inpatients and six healthy volunteers. The effects of long-term administration were then assessed in depressed patients after 4 weeks of treatment. Sedative effects of the drug were more pronounced in healthy subjects while sleep parameters of depressed patients seemed less sensitive to the drug. Chronic effects tended to correct most of the sleep disturbances seen in depressed subjects with respect to the natural organization of sleep. The major sleep effect of trimipramine concerned REM latency which was lengthened in both groups, independently of the treatment protocol.     

Biological and clinical features of recurrent brief depression: a comparison with major depressed and healthy subjects.

Recurrent brief depression (RBD) has recently been proposed as a new subtype of affective disorder characterized by episodes of major depression which last less than two weeks. The aim of this study was to further evaluate the validity of this putative subtype by means of clinical and biological data. DST, TSH response to TRH and sleep EEG variables were compared in 25 RBD patients sex- and age-matched to 25 major depressed (MD) and 25 healthy subjects. Family history, age at onset, and psychiatric comorbidity did not discriminate RBD from MD. Recurrent unipolar depression was found to be more prevalent in MD. Although less severely depressed during the biological tests, patients with RBD did not significantly differ from those with MDD on basis of DST non-suppression, blunted TSH response and shortening of REM latency. Compared to controls, a greater sleep onset latency was observed both in RBD and MD and a lower total sleep time in MD patients only. These results suggest that RBD could be viewed as a subtype of affective disorder sharing many characteristics with MDD.     

A polysomnographic study in young psychiatric inpatients: major depression, anorexia nervosa, bulimia nervosa

The baseline EEG sleep patterns of 10 young depressed patients, 20 patients with anorexia nervosa, 10 patients with bulimia nervosa, and 10 healthy subjects were found to be indistinguishable, except for an increased REM density in the depressed patients. In eating disorder patients, a concomitant major depressive episode had no influence on EEG sleep. The results of the cholinergic REM sleep induction test revealed a significantly faster induction of REM sleep in the depressed patients when compared with the eating disorder patients and the control subjects. This indicates a subthreshold hypersensitivity of the REM sleep triggering cholinergic transmitter system in depressives, but not in eating disorder patients.     

Comparison of EEG sleep measures in healthy full-term and preterm infants at matched conceptional ages.

Continuous electroencephalogram (EEG) sleep studies were obtained on healthy full-term and preterm infants at matched conceptional ages. Studies were recorded under environmentally controlled conditions. Eighteen healthy preterm infants were matched to 18 full-term infants based on conceptional age, sex, race and socioeconomic class. The initial 3 hours of a 12-hour recording were simultaneously recorded on paper and computer. The visually scored data based on the paper recordings for sleep architecture and continuity measures were studied. Differences in each sleep organization for the preterm infants included the following: a longer ultradian sleep cycle (70 minutes vs. 53 minutes, p = 0.02) was noted. More abundant tracé alternant (34% vs. 28%, p = 0.02) and less abundant low-voltage irregular active sleep (13% vs. 17%, p = 0.05) were noted. Although no differences were observed for sleep latency and efficiency, the preterm infants had fewer numbers and shorter durations of arousals, fewer body movements and rapid eye movement (REM) (p < 0.01), particularly during quiet sleep. The extrauterine experience or the earlier birth of the preterm infant may influence specific sleep architecture and continuity measures when compared with the sleep of full-term infants who experienced a complete intrauterine gestation.     

Symposium: Normal and abnormal REM sleep regulation: REM sleep in depression-an overview

Abnormalities of REM sleep, i.e. shortening of REM latency, lengthening of the duration of the first REM period and heightening of REM density, which are frequently observed in patients with a major depressive disorder (MDD), have attracted considerable interest. Initial hopes that these aberrant patterns of sleep constitute specific markers for the primary/endogenous sub-type of depression have not been fulfilled. The specificity of REM sleep disinhibition for depression in comparison with other psychopathological groups is challenged as well. Demographic variables like age and sex exert strong influences on sleep physiology and must be controlled when searching for specific markers of depressed sleep. It is still an open question whether abnormalities of sleep are state- or trait-markers of depression. Beyond baseline studies, the cholinergic REM induction test (CRIT) indicated a heightened responsitivity of the REM sleep system to cholinergic challenge in depression compared with healthy controls and other psychopathological groups, with the exception of schizophrenia. A special role for REM sleep in depression is supported by the well-known REM sleep suppressing effect of most antidepressants. The antidepressant effect of selective REM deprivation by awakenings stresses the importance of mechanisms involved in REM sleep regulation for the understanding of the pathophysiology of depressive disorders. The positive effect of total sleep deprivation on depressive mood which can be reversed by daytime naps, furthermore emphasizes relationships between sleep and depression. Experimental evidence as described above instigated several theories like the REM deprivation hypothesis, the 2-process model and the reciprocal interaction model of nonREM-REM sleep regulation to explain the deviant sleep pattern of depression. The different models will be discussed with reference to empirical data gathered in the field.     

Temporal characteristics of delta activity during NREM sleep in depressed outpatients and healthy adults: group and sex effects

STUDY OBJECTIVES: The primary aim was to evaluate group and sex differences in delta activity across non-rapid eye movement (NREM) sleep in depressed patients and healthy controls. DESIGN: Repeated-measures ANOVA contrasted delta power, amplitude and incidence in the first three NREM periods (stages 2, 3, and 4) of sleep. The time course of delta activity was evaluated with exponential regressions. Age effects on delta were evaluated with linear regression analysis. SETTING: Two consecutive nights were spent in the laboratory, the first of which served as adaptation. PATIENTS OR PARTICIPANTS: Twenty-two (9 men, 13 women) symptomatic, but unmedicated, outpatients with major depressive disorder (MDD) and 23 healthy controls (15 men, 8 women) participated in the study. MEASUREMENTS AND RESULTS: Delta power and amplitude showed significant group by sex interactions. Men with MDD showed lower power and amplitude in NREM sleep compared to women with MDD, but did not differ significantly from controls. However, the time course of delta power and amplitude was significantly different in men with MDD, with lower accumulation and slower dissipation across NREM sleep than all other groups. Women with MDD showed no evidence of lower delta power and amplitude or an abnormal time course compared to control women or men. Age had a differential influence on delta activity between the groups, with little age-related change in delta activity in the depressed groups. CONCLUSIONS: It was concluded that slow-wave sleep deficiencies may be characteristic of men, but not women, with MDD. It was also concluded that the influence of age on delta activity varied as a function of both psychiatric status and sex.     

Sex and age differences in sleep macroarchitecture in childhood and adolescent depression

SUBJECT OBJECTIVE: To evaluate age and sex differences in sleep macroarchitecture in children and adolescents with major depressive disorder. DESIGN: Ninety-seven (50 F, 47 M) symptomatic unmedicated depressed outpatients were compared with 76 healthy controls (42 F, 34 M) matched for age and sex. SETTING: Participants spent 2 consecutive nights in the sleep laboratory. PARTICIPANTS: One hundred seventy-three children and adolescents, aged 8 to 18 years. MEASUREMENTS AND RESULTS: Significant group-by-age-by-sex interactions were evident for total sleep period, percentage of Stage 1 sleep, percentage of Stage 2, percentage of slow-wave sleep, and rapid eye movement (REM) sleep latency. The depressed adolescent boys had the greatest sleep disturbance with the highest amount of percentage of Stage 1 sleep, the shortest REM latency, and the least percentage of slow-wave sleep and number of minutes of slow-wave sleep in the first non-REM period. There were minimal age differences in sleep parameters between depressed children and adolescent girls. Within age groups, the sex differences were minimal in the healthy controls. The sex differences within the depressed group were substantially larger than controls. CONCLUSIONS: These findings suggest a differential developmental influence on sleep in early-onset depression that is heavily dependent on sex. Sex differences are substantially smaller in healthy individuals compared with those with depression, in agreement with previous studies in depressed adults.     

Slow-wave sleep: do young adult men and women age differently?

The differential effects of ageing on polysomnographic and EEG spectral characteristics of sleep were explored in men and women between the ages of 20 and 40. Men and women in their twenties were found to have similar percentages of slow-wave sleep (SWS) (% Stage 3 and 4) and mean EEG slow wave activity (quantified by spectral analysis). Significant reductions in the percentage of SWS and mean slow wave activity over the night occurred in men during their thirties but not in the women. This suggests that gender difference in SWS may emerge between age 30 and 40 in young adults. Men in this sample were also found to have significant increases in Stage 2 sleep, and decreases in REM sleep time, REM activity, REM density and REM intensity. No significant effects of age were found for women in any visually scored sleep variables. Both men and women had age related reductions in spectral power in the spindle frequencies. Taken together, these findings suggest that the sleep of men and women over age 20–40 may age differently.     

Effects of playing a computer game using a bright display on presleep physiological variables, sleep latency, slow wave sleep and REM sleep

Epidemiological studies have shown that playing a computer game at night delays bedtime and shortens sleeping hours, but the effects on sleep architecture and quality have remained unclear. In the present study, the effects of playing a computer game and using a bright display on nocturnal sleep were examined in a laboratory. Seven male adults (24.7+/-5.6 years old) played exciting computer games with a bright display (game-BD) and a dark display (game-DD) and performed simple tasks with low mental load as a control condition in front of a BD (control-BD) and DD (control-DD) between 23:00 and 1:45 hours in randomized order and then went to bed at 2:00 hours and slept until 8:00 hours. Rectal temperature, electroencephalogram (EEG), heart rate and subjective sleepiness were recorded before sleep and a polysomnogram was recorded during sleep. Heart rate was significantly higher after playing games than after the control conditions, and it was also significantly higher after using the BD than after using the DD. Subjective sleepiness and relative theta power of EEG were significantly lower after playing games than after the control conditions. Sleep latency was significantly longer after playing games than after the control conditions. REM sleep was significantly shorter after the playing games than after the control conditions. No significant effects of either computer games or BD were found on slow-wave sleep. These results suggest that playing an exciting computer game affects sleep latency and REM sleep but that a bright display does not affect sleep variables.     

Sleep architecture and sleep apnea in patients with Cushing's disease.

Patients with Cushing's syndrome (CS) frequently have sleep complaints. We evaluated sleep polysomnographically in 22 patients, including 17 with pituitary-ACTH-dependent Cushing's disease (CD) and five with CS from an adrenal tumor. Data were compared to healthy controls of comparable age. Seven patients (32%) demonstrated at least mild sleep apnea (> or = 9.4 events/hour), and four of 22 (18%) had > or = 17.5 events/hour. The apneic CD and CS patients had a trend for a greater complaint of excessive daytime sleepiness. Both apneic and nonapneic groups had considerable snoring and obesity. The electroencephalographic (EEG) sleep of nonapneic patients was compared to that of normal subjects. Nonapneic CD patients differed strikingly from healthy volunteers in sleep continuity and architecture, demonstrating lighter, fragmented sleep. Rapid eye movement (REM) sleep in CD patients bore many similarities to the sleep of patients with major depression, with REM latency being significantly shortened and REM density significantly increased. Continued examination of EEG sleep in CD patients may shed light on similarities in pathophysiology between CD and major depression, disorders which are characterized by both a dysfunction of the hypothalamic-pituitary-adrenal axis and alterations in mood.     

Sleep patterns related to menstrual cycle phase and premenstrual affective symptoms

An ovulatory menstrual cycle is characterized by fluctuating levels of progesterone. Progesterone, a gonadal hormone known for its soporific and thermogenic effects, is present in negligible levels prior to ovulation and in high levels after ovulation. To describe and compare sleep patterns in relation to ovulatory cycles and premenstrual mood state, sleep was monitored in healthy women at two phases of the menstrual cycle. Results indicated that rapid-eye-movement (REM) latency was significantly shorter during the postovulatory (luteal) phase compared to the preovulatory (follicular) phase, but there was no significant difference in latency to sleep onset or the percentage of REM sleep. While there were no menstrual cycle phase differences in the percentages of various sleep stages, the women with negative affect symptoms during the premenstruum demonstrated significantly less delta sleep during both menstrual cycle phases in comparison with the asymptomatic subjects.     

Effects of intravenous catheter on sleep in healthy men and in depressed patients

The effects of intravenous catheter and nocturnal blood samplings at frequent intervals on sleep electroencephalogram (EEG) variables were investigated in 8 male healthy controls and 12 depressed patients, who were studied in the same experimental conditions. After one night of habituation, sleep was recorded during 4 consecutive nights in the sleep laboratory. A catheter was inserted around noon the day before the fourth night, and blood was sampled every 15 min for 25 h. The night-to-night comparison of sleep EEG variables did not show significant sleep continuity modifications in the control subjects, other than a weak trend toward an increase in nocturnal awakenings during the night with the catheter. A lengthening of sleep onset latency during the fourth night was found in the depressed patients. No significant changes were detected in percentage of rapid eye movement (REM) sleep in the two groups. However, a gradual increase in Stage 3 was observed across the 4 nights in the control subjects. These results indicate that intravenous blood sampling via a catheter can be performed without inducing significant disruption of sleep length and structure.     

Sleep microstructure around sleep onset differentiates major depressive insomnia from primary insomnia

In the present study we investigate whether alterations of sleep propensity or of wake propensity are implicated in sleep initiation disturbances encountered in major depressive insomnia and in primary insomnia. For this purpose, the time course of electroencephalogram (EEG) power density during the period preceding sleep onset and during the first non-rapid eye movement (REM) period was examined in three age and gender matched groups of 10 women and 11 men (healthy controls, primary insomniacs and depressive insomniacs). In contrast to healthy controls and depressive insomniacs, patients with primary insomnia did not experience a gradual decrease of their alpha and beta1 power during the sleep onset period and had a lower delta activity in the 5 min preceding sleep onset. Compared with the two other groups, depressive patients exhibit less dynamic changes in slow wave activity during the first non-REM period. The present results suggest that hyperarousal (high 'Process W') may mainly be implicated in the sleep initiation difficulties of primary insomniacs whereas the homeostatic sleep regulation process seems to be partially maintained. In our major depressed patients, the sleep initiation disturbances appeared to relate to a lower sleep pressure (low 'Process S') rather than to hyperarousal. This study supports the idea that different mechanisms are implicated in sleep disturbances experienced by primary insomniacs and major depressive insomniacs.     

Sex differences in delta and alpha EEG activities in healthy older adults

STUDY OBJECTIVES: To examine sex effects on sleep stages and electroencephalogram (EEG) spectral power in older adults. DESIGN: Sleep was polygraphically recorded for 2 consecutive nights, and blood was sampled during the last 24 hours. SETTING: The University of Chicago Clinical Research Center. PARTICIPANTS: Two groups of healthy nonobese older subjects: 10 men (59 +/- 2 years), and 10 postmenopausal women (63 +/- 2 years). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: A spectral analysis of the EEG was performed in the delta and alpha bands. There were no sex differences in sleep stages. Blood sampling resulted in reductions of total sleep time, sleep maintenance, slow-wave sleep, and absolute delta activity that were all larger in women than in men. In absolute values, delta and alpha activities in non-rapid eye movement (NREM) and rapid eye movement (REM) sleep were higher in women than in men, but, for delta activity, the sex differences were larger in REM than in NREM sleep. In women, but not in men, absolute delta activity in REM was decreased during blood sampling and was strongly correlated with absolute delta activity in NREM. Delta activity in REM did not dissipate across the night in either group. When normalized for the activity in REM sleep, the sex difference in delta activity in NREM sleep was reversed, with lower activity in women. CONCLUSIONS: Sex differences in sleep EEG variables are present in older adults. When normalized, delta activity in older women is lower than in older men, which may be more consistent with sex differences in subjective complaints, in fragility of sleep in the presence of environmental disturbances, and in the relationship to growth-hormone release.     

EEG sleep, depression, and aging

—To date little attention has been paid to the posssible age-dependent relationships of EEG sleep measures in depression or to the implications of such relationships for diagnostic sensitivity and specificity. In a study of 108 patients with major depressive disorders (67 inpatients, 41 outpatients), age was shown to be a very powerful determinant of electroencephalographic (EEG) sleep patterns. Thus, among other sleep variables, sleep efficiency, delta sleep percent, and REM latency all showed significant linear declines with increasing age. Similar trends were seen in both inpatients and outpatients. Some variables were without age trends (age-stable), including sleep latency, REM sleep percent, and REM activity. These findings confirm those of an earlier report from our laboratory [45] and suggest that age-corrected sleep variables can be developed for clinical diagnostic application. Thus, using normative data from Gillin et al. [19] for comparison, a sensitivity level of 65% for age-corrected REM latency was demonstrated, together with a specificity of 95% and a diagnostic confidence of 92%. Data from a pilot study comparing EEG sleep measures in depression and dementia are also presented; these data suggest the potential utility of EEG sleep measures in the differential diagnosis of these two disorders, especially in patients with mixed symptoms. Additional areas for further research are reviewed with enumeration of specific testable hypotheses.     

The sleep structure of patients with anxiety disorders in comparison to that of healthy controls and depressive patients under baseline conditions and after cholinergic stimulation.

This study investigated sleep EEG during placebo and after cholinergic stimulation with RS 86 in 36 healthy subjects, 34 patients with major depression and 20 patients with anxiety disorders. Cholinergic stimulation with RS 86 led to a decrease of slow wave sleep and REM latency. RS 86 had a more profound impact on REM latency in patients with major depression than in healthy controls and patients with anxiety disorders. Six out of 36 healthy controls, three out of 20 patients with anxiety disorders and 24 of 34 patients with depression displayed sleep onset REM periods after cholinergic stimulation. Also effects on REM density and duration of the first REM period were more pronounced in major depression. Even in those patients with anxiety disorders and a secondary major depression no depression-like sleep abnormalities could be provoked. The results underline the usefulness of the cholinergic REM induction test to differentiate patients with major depression from those with other psychiatric disorders. The results can be interpreted as further evidence for the cholinergic-aminergic imbalance model of depression and for the reciprocal interaction model of nonREM-REM regulation.