REM Density Research Articles

Relationship between ethnicity and sleep patterns in normal controls: implications for psychopathology and treatment

The purpose of the study was to examine ethnic influences on sleep regulation. Seventy-three normal volunteers from four ethnic groups (17 African-Americans, 10 Asians, 30 Caucasians and 16 Hispanics) were studied for two consecutive nights with sleep polysomnography recordings in the laboratory. The subjects were in good physical and psychological health, and were asymptomatic with respect to sleep/wake complaints or sleep disorders. With the exception of minor differences, sleep continuity, sleep architecture and rapid eye movement (REM) sleep patterns were comparable among the four groups. African-Americans had evidence of more stages 1 and 2 and diminished stage 4 sleep, whereas the Hispanics had higher REM density. These preliminary findings suggest that sleep patterns are remarkably similar across cultures. There are, however, important cross-ethnic differences, specifically in the depth of sleep and in phasic REM measures. Because sleep disturbances are common symptoms of emotional disorders and since many psychoactive agents affect sleep, cross-ethnic differences in sleep patterns may have potential implications for the treatment and prevention of psychiatric disorders.

Olanzapine acute administration in schizophrenic patients increases delta sleep and sleep efficiency

Background: A delta sleep deficit has been observed in schizophrenic patients. Olanzapine is a novel atypical antipsychotic agent with affinity at dopaminergic, serotonergic, muscarinic, adrenergic and histaminergic binding sites. The present study was designed to analyze a sleep promoting effect reported for olanzapine. Methods: Twenty schizophrenic patients (DSM-IV) were studied, who were drug free and inpatients. Patients slept for 5 consecutive nights in the sleep unit as follows: one acclimatization night; two baseline nights (the first for sleep disorder screenings); and two olanzapine nights (10 mg olanzapine, one hour before sleep onset). Results: Sleep continuity variables and total sleep time showed an overall improvement with olanzapine. Waking time was reduced since the first night of olanzapine administration. The main sleep architecture changes were: reduction in sleep stage 1, while sleep stage 2 and delta were significantly enhanced. Rapid eye movement density was also increased by the second olanzapine night. Conclusions: Total sleep improvement was due to the increase in sleep stages 2 and delta sleep. This may be related to serotonergic antagonistic properties of olanzapine. Olanzapine seems to have a sleep promoting effect in schizophrenic patients.

Transdermal scopolamine alters phasic REM activity in normal young adults.

Transdermal scopolamine has been widely used for the prevention of motion-sickness by travelers due to its potent anticholinergic effects and the ease of administration. Nevertheless, its effects on sleep physiology are not known, despite the wellknown fact that the administration of scopolamine as an injection or an oral form could influence the sleep architecture, especially prolonging rapid eye movement (REM) sleep latency and shortening duration of REM sleep. This study aimed to measure the influence of transdermal scopolamine on REM sleep in order to examine whether it affects REM sleep as in the previous studies. We studied eight young healthy male adults polysomnographically for three nights including one adaptation night in a double blind crossover design and compared REM sleep-related variables between sleeps with and without scopolamine patch of 1.5 mg. We found no differences in tonic REM sleep measures such as REM duration and REM latency, but phasic REM sleep measures such as total REM activity (p < 0.05) and total REM density (p < 0.05) were significantly suppressed by the transdermal scopolamine; REM densities of the first (p < 0.05) and the second (p < 0.05) REM sleep periods as well as REM activity of the fourth REM sleep period (p < 0.05) were decreased significantly on the scopolamine patch nights compared with placebo patch nights. These results suggest that phasic REM components reflect cholinergic mechanism in the central nervous system (CNS) even at the lowest commercial dose, and could be useful markers of CNS cholinergic activities in the future research.

Effects of Fluoxetine on the Polysomnogram in Outpatients with Major Depression

This study investigated the effects of open-label fluoxetine (20 mg/d) on the polysomnogram (PSG) in depressed outpatients (n = 58) who were treated for 5 weeks, after which dose escalation was available (⩽40 mg/d), based on clinical judgment. Thirty-six patients completed all 10 weeks of acute phase treatment and responded (HRS-D⩽ 10). PSG assessments were conducted and subjective sleep evaluations were gathered at baseline and at weeks 1, 5, and 10. Of the 36 subjects who completed the acute phase, 17 were reevaluated after 30 weeks on continuation phase treatment and 13 after approximately 7 weeks (range 6–8 weeks) following medication discontinuation. Acute phase treatment in responders was associated with significant increases in REM latency, Stage 1 sleep, and REM density, as well as significant decreases in sleep efficiency, total REM sleep, and Stage 2 sleep. Conversely, subjective measures of sleep indicated a steady improvement during acute phase treatment. After fluoxetine was discontinued, total REM sleep and sleep efficiency were found to be increased as compared to baseline.

First-cycle REM density in never-depressed subjects with borderline personality disorder

Background: There is much interest in the identification of polysomnographic markers of liability to the mood disorders that may predate the onset of illness in high-risk subjects, and/or remain altered after remission. One such putative marker is rapid eye movement (REM) density during the first REM period.Methods: Never-depressed subjects with borderline personality disorder (BPD) as a group at high risk for the mood disorders were compared by continuous 48-hour ambulatory electroencephalographic monitoring to age- and gender-matched controls.Results: Subjects with BPD had significantly higher REM density during the first REM period. One man with BPD who later committed suicide had REM density values exceeding the mean value of his group by 2 SD.Conclusions: These data extend the view that REM density in the first REM period can be a marker of liability to the mood disorders, as it is present in a group of young subjects at heightened risk for depression. Biol Psychiatry 1999;45:1056–1058 © 1999 Society of Biological Psychiatry

Rapid eye movement sleep changes during the adaptation night in combat veterans with posttraumatic stress disorder

Background: Hyperarousal in posttraumatic stress disorder (PTSD) is manifested during sleep as well as waking. Elevated rapid eye movement sleep (REMS) phasic activity, likely signifying central nervous system alerting, has been identified in PTSD. The authors reasoned that PTSD compared to control subjects would show particularly increased REMS phasic activity on the first night of polysomnography, with adaptation to a novel environment. Methods: First-night polysomnograms of 17 veterans with PTSD were compared with those of 11 control subjects. Sleep was also studied in subsets of both groups over two nights. Results: On the first night, the PTSD subjects had a higher density of rapid eye movements in the first REMS period. This measure was increased on the first compared to the second night, but there was no interaction effect between night and group. Conclusions: REMS changes are again demonstrated in veterans with PTSD. Introduction to a novel environment activated a REMS phasic process, but not differentially in PTSD compared to control subjects.

Polygraphic sleep criteria as predictors of successful aging: an exploratory longitudinal study

Background: A cohort of 57 elderly healthy volunteers (34 male, 23 female) was studied in a sleep laboratory on four consecutive nights when their average age was 63.5 ± 3.7 years. Thirty subjects (20 male, 10 female) were assessed 14 years later; 21 had either died in the meantime or were very ill, and 6 did not participate for other reasons. Methods: Two operationalizations of successful aging were applied: survival in relatively good health (30 survivors vs. 21 nonsurvivors), and cognitive competence as assessed in the survivors by means of tests of cognitive function. Results: Whereas none of the sleep characteristics determined at baseline distinguished the survivors from the nonsurvivors, several parameters [REM (rapid eye movement) sleep latency, REM density, and NREM (non-REM) shifts] were significantly correlated with one or more measures of cognitive functioning at follow-up. These polygraphic sleep parameters also distinguished a subgroup of cognitively fully competent subjects from those who, according to their performance in tests of cognitive function, could be considered as mildly demented. Conclusions: While the REM latency and density findings support the theory of a functional link between brain cholinergic activity, timing, and density of REM sleep and cognitive functioning, the positive association between the number of NREM shifts at baseline and cognitive performance 14 years later is difficult to explain. It is suggested that the findings of the present study, in particular the potential predictive value of REM latency and REM density for cognitive functioning in the old, need replication in other subject samples followed for similar time periods.

The tryptophan depletion test. Impact on sleep in healthy subjects and patients with obsessive-compulsive disorder.

The tryptophan depletion test is a research tool to study the functional consequences of decreasing the brain serotonin metabolism. Since serotonin is involved in sleep regulation and assumed to be of high importance in the etiology of psychiatric disorders, the acute polysomnographic effects of tryptophan depletion were studied in healthy subjects and patients with obsessive compulsive disorder (OCD). According to the reciprocal interaction model of non-REM and REM-sleep regulation we expected that tryptophan depletion in healthy controls should provoke alterations of sleep similar to depression, whereas we assumed that these effects would be more pronounced in patients with OCD. 12 healthy subjects with a mean age of 34 years and 12 patients suffering from OCD with a mean age of 30 years had 4 polysomnographic investigations. After 1 adaption and 1 baseline night subjects received a low protein diet on day 3 and 4 until midday. On day 4 at 18.00 h subjects ingested an aminoacid mixture devoid of tryptophan. This procedure resulted in a decrease of 85% in healthy subjects and 80% in OCD patients at 22.00 h. The tryptophan depletion led to more pronounced disturbances of sleep continuity in OCD patients than in healthy subjects in terms of an increase of wake time and a decrease of total sleep time. In both groups a decrease of sleep stage 2 could be observed. Healthy subjects showed significant alterations of phasic REM parameters as REM density and total number of rapid eye movements, what was not the case for OCD patients. Our results indicate the important role of the serotonergic system for sleep maintainance and the phasic aspects of REM sleep. Furthermore our data demonstrate that the tryptophan depletion test is a useful tool to evaluate the hypothesis of a serotonergic involvement in sleep regulation and the etiology of psychiatric disorders.

Polysomnography and depressive symptoms in primary alcoholics with and without a lifetime diagnosis of secondary depression and in patients with primary major depression

Background: There is evidence suggesting that there is: (1) additive polysomnographic effects of alcoholism and depression; and (2) elevated baseline REM density in primary alcoholics with (PASD) and without lifetime history of secondary depression (NPA). Methods: 23 PASDs, 59 NPAs, and 23 primary major depression patients (PMD) underwent polysomnography. Any drinking within 3 months after a 1-month inpatient alcohol rehabilitation defined relapse. Results: PASDs' polysomnography was more like NPAs than PMDs. Polysomnography reflected 3-month sobriety status more than diagnosis. Limitations: Not all PASD's met full major depression criteria upon admission. Conclusions: Alcoholism affected polysomnography more than depression. Elevated admission REM density predicted 3-month relapse in PASDs and NPAs.

Is there a relationship between delta sleep at night and afternoon cerebral blood flow, assessed by HMPAO-SPECT in depressed patients and normal control subjects? Preliminary data

We wished to explore the relationships between waking HMPAO uptake and visually scored polysomnography. We hypothesized that HMPAO activity would correlate positively with slow wave sleep measures the same night. Eight unmedicated unipolar patients with current DSM-IV major depression (17-item Hamilton Depression Rating Scale Score 21.5±2.9) and seven control subjects received polysomnography on 2 consecutive nights. On the afternoon following the adaptation night, subjects received cerebral SPECT, with 15 mCi Tc-99m-HMPAO injected while subjects performed the Continuous Performance Task. Patients and control subjects did not significantly differ on demographic, polysomnographic, and SPECT variables. Slow wave sleep measures correlated positively (Spearman's) with global and regional tracer activity for depressed ( n=8), control ( n=7) and combined groups ( n=15); in other words, the greater the global or regional afternoon HMPAO uptake, the greater the slow wave sleep measures were the same night. In addition, the greater the waking afternoon global or regional HMPAO activity, the faster subjects fell asleep and the less Stage 2% they had. In patients, global and regional HMPAO activity correlated positively with REM density. Positive correlations between waking tracer activity and subsequent slow wave measures are consistent with previous hypotheses linking slow wave sleep with brain energy conservation and restoration. Further study is needed to determine whether these functional relationships differ in depression.

Polysomnographic studies of Lesch–Nyhan syndrome

Three cases of Lesch–Nyhan syndrome (LNS) were examined by polysomnography to assess the brainstem function, and to determine the causes of the neurological manifestations and sudden death in this syndrome. In the two older cases, the amount of slow wave and rapid eye movement (REM) sleep, the REM density and the frequency of REM bursts were decreased. In the youngest case, symmetrical phasic movements of all four limbs were observed at all sleep stages other than REM sleep. Although movements other than these symmetrical body movements appeared to be normal in this case, the frequency of twitch movements showed an abnormal pattern in each sleep stage in the two older cases. These findings suggest that in the brainstems of younger cases with LNS the REM-non REM generator as well as multiple neurotransmitter systems influencing body movements during sleep remain relatively normal, but become progressively impaired in adult cases. Severe obstructive apnea was observed in one case with hypothyroidism, but there were no respiratory abnormalities in other two cases.

A laboratory study of sleep and dreaming in a case of Asperger's Syndrome.

Asperger's Syndrome (AS) is a pervasive developmental disorder whose continuity with High-Functioning Autism is still a matter of debate. Clinical observations suggest that patients with AS may present the same sleep disorders as autistic patients, including difficulties in initiating and maintaining sleep as well as poor dream recall. We recorded the sleep of a 25-year-old male patient with AS for two nights using a full EEG montage and compared the second night to that of a group of normal participants. We found low levels of slow wave sleep (SWS: stages 3 + 4), high levels of stage 1, and a large number of awakenings. The organization of REM sleep was unremarkable, including normal REM density. Analyses of phasic EEG events revealed a very low incidence of sleep spindles and a normal number of K-complexes over bilateral frontal and central EEG leads. In order to collect dream reports, the patient was awakened three times over two nights following at least 15 minutes of REM sleep in each case. On each occasion the patient was not aware of any mental activity happening just prior to awakening. These observations are discussed with regards to the connections that may exist between EEG sleep spindle activity, selective attention, and the capacity to generate a dream report.

Increased REM Sleep Density at Admission Predicts Relapse by Three Months in Primary Alcoholics with a Lifetime Diagnosis of Secondary Depression

Background: Having previously reported that 3-month relapse was associated with increased admission REM pressure in nondepressed primary alcoholics, we hypothesized that baseline polysomnography would predict outcome in primary alcoholics with a lifetime diagnosis of secondary depression. Methods: Twenty-one primary alcoholics with secondary depression received polysomnography and the Hamilton Depression Rating Scale during the first and fourth weeks of a 1-month inpatient alcohol treatment program. Exclusion criteria included serious illness, current major alcohol withdrawal symptoms, other Axis I diagnoses, sleep apnea, nocturnal myoclonus, and psychoactive substances within 14 days of polysomnography. Relapse was defined as drinking any alcohol between hospital discharge and 3-month follow-up. Results: Relapsers’ total sleep time was reduced, and REM density (reflecting REM sleep ocular activity) was increased significantly throughout admission compared with abstainers. Sleep continuity and Hamilton scores improved by discharge in sober and relapsing alcoholics. Factors derived from admission REM latency, REM percent, and REM density predicted sobriety vs. relapse within 3 months after hospital discharge in 76% of patients. Admission REM density was greater, and total sleep time was less in relapsers than in patients sober at 3 months. Conclusions: Results suggest that increased REM density and decreased total sleep time at about 2–4 weeks of abstinence predict relapse by 3 months in depressed alcoholics.

Impact of experimentally induced serotonin deficiency by tryptophan depletion on sleep EEC in healthy subjects

The tryptophan depletion test is a research strategy to investigate the functional consequences of decreasing the brain serotonin metabolism. Because serotonin is involved in sleep regulation and the regulation of affective states, we studied the acute polysomnographic effects of tryptophan depletion and expected to induce similar changes of sleep EEG as observed in depressed patients. A total of 12 healthy subjects (mean age 34 +/- 3 years) had eight polysomnograms, divided in two blocks of 4 consecutive nights. After one adaptation and 1 baseline night, subjects received a low-protein diet on day 3 and 4 until midday. On day 4 at 18.00 h, they drank an amino acid mixture either devoid of tryptophan or containing 2.3 g of tryptophan (placebo control) in randomized and double-blind order, resulting in an 85% decrease (tryptophan depletion) and a 144% increase (placebo control) of serum tryptophan at 22.00 h. After tryptophan depletion but not placebo, significant effects on sleep EEG were observed in terms of decreased non-rapid eye movement (non-REM) stage 2, increase of wake %, and of rapid eye movement (REM) density compared with baseline. REM latency was not altered, however the first and second REM period interval were significantly shorter after tryptophan depletion. This study underlines the impact of the serotonergic system on sleep maintenance and on REM sleep.

The value of REM sleep parameters in differentiating Alzheimer's disease from old-age depression and normal aging

Pseudodementia as a common trait in elderly depressives presents a major problem in gerontopsychiatry, especially for the differential diagnosis between Old-Age Depression (OAD) and Dementia of the Alzheimer Type (DAT). The present polysomnographic study examined parameters of sleep continuity, sleep architecture, and REM sleep to differentiate DAT from OAD. The investigation was based on the theoretical framework of the cholinergic-aminergic imbalance model of depression, the cholinergic deficit hypothesis of Alzheimer's disease and the reciprocal interaction model of Non-REM/REM sleep regulation, according to which REM sleep parameters should have high discriminative value to differentiate OAD and DAT. We investigated 35 DAT patients, 39 OAD patients and 42 healthy controls for two consecutive nights in the sleep laboratory. The DAT patients were in relatively early/mild stages of the disease, the severity of depression in the OAD group was moderate to severe. Depressed patients showed characteristic ‘depression-like’ EEG sleep alterations i.e. a lower sleep efficiency, a higher amount of nocturnal awakenings and decreased sleep stage 2. Sleep continuity and architecture in DAT was less disturbed. Nearly all REM sleep measures differentiated significantly between the diagnostic groups. OAD patients showed a shortened REM latency, increased REM density and a high rate of Sleep Onset REM periods (SOREM), whereas in DAT REM density was decreased in comparison to control subjects. REM latency in DAT was not prolonged as expected. To assess the discriminative power of REM sleep variables a series of discriminant analyses were conducted. Overall, 86% of patients were correctly classified, using REM density and REM latency measures. Our findings suggest that REM density as an indicator of phasic activity appears to be more sensitive as a biological marker for the differential diagnosis of OAD and DAT than REM latency. The results support the role of central cholinergic neurotransmission in REM sleep regulation and the pathogenesis of DAT and OAD.

EEG sleep in African‐American patients with major depression: A historical case control study

This study was designed to evaluate the effect of race, specifically African-American, on electroencephalographic (EEG) sleep and clinical symptom profile in unipolar major depression. A clinical research database was used to identify appropriate subjects and a double-matched historical case-control design was implemented. African-American depression patients were double matched within protocol to Euro-American depressed patients. Age, sex, and protocol of origin were matching variables. African-American depressed patients had less total sleep, less slow wave sleep, more stage 2 sleep, longer rapid eye movement (REM) sleep latency, less REM sleep, and lower REM density than Euro-American depressed patients. African-American depressed patients did not differ from Euro-American patients in symptom severity, age of onset, number of episodes, socio-economic status, and, as planned, did not differ in age and sex distribution. Depressive symptom constellation also did not distinguish the two groups. African-American depressed patients demonstrated differences in EEG sleep profile, with less total sleep, overall lighter nonREM sleep, and relatively preserved REM sleep, despite a clinical symptom profile that did not differ from Euro-American depressed patients. The sleep profile appeared to be consonant with the sleep findings in chronic insomnia. The pathological implications of these differences remained to be explored in careful prospective studies of African-American depressed patients and in well-characterized, racially matched normal control comparisons. Depression and Anxiety 8:58–64, 1998. © 1998 Wiley-Liss, Inc.

EEG sleep in African-American patients with major depression: A historical case control study

This study was designed to evaluate the effect of race, specifically African-American, on electroencephalographic (EEG) sleep and clinical symptom profile in unipolar major depression. A clinical research database was used to identify appropriate subjects and a double-matched historical case-control design was implemented. African-American depression patients were double matched within protocol to Euro-American depressed patients. Age, sex, and protocol of origin were matching variables. African-American depressed patients had less total sleep, less slow wave sleep, more stage 2 sleep, longer rapid eye movement (REM) sleep latency, less REM sleep, and lower REM density than Euro-American depressed patients. African-American depressed patients did not differ from Euro-American patients in symptom severity, age of onset, number of episodes, socio-economic status, and, as planned, did not differ in age and sex distribution. Depressive symptom constellation also did not distinguish the two groups. African-American depressed patients demonstrated differences in EEG sleep profile, with less total sleep, overall lighter nonREM sleep, and relatively preserved REM sleep, despite a clinical symptom profile that did not differ from Euro-American depressed patients. The sleep profile appeared to be consonant with the sleep findings in chronic insomnia. The pathological implications of these differences remained to be explored in careful prospective studies of African-American depressed patients and in well-characterized, racially matched normal control comparisons.

Sleep and Treatment Response in Depression

Some of the changes in sleep architecture associated with major depression, such as increased REM density and poor sleep efficiency, return to normal with remission of depression (state variables); while others, such as decreased slow wave sleep and reduced delta sleep ratio, tend to persist (trait variables). Reduced REM latency has …

Rapid eye movement sleep correlates with the overall activities of the hypothalamic-pituitary-adrenal axis and sympathetic system in healthy humans.

To assess the association of the overall amount of rapid eye movement (REM) sleep and the activities of the hypothalamic-pituitary-adrenal axis and sympathetic system, we performed polysomnography and measured 24-h urinary free cortisol and catecholamine excretion in 21 healthy adults. After an adaptation night, each subject was recorded in the sleep laboratory for 3 consecutive nights while 24-h urine specimens were collected. Urinary free cortisol, epinephrine, dihydroxyphenylglycol, and dihydroxyphenylacetic acid levels were significantly and positively correlated with the average values of percent REM sleep (P < 0.05). There were no correlations between hormone values and REM latency, other variables of REM distribution, or REM density, an index of phasic activity during REM sleep. The positive correlations between stress system activity and REM sleep are consistent with hormonal and sleep alterations in melancholic depression, a state characterized by increased cortisol and catecholamine secretion.

REM Sleep Disinhibition at Sleep Onset: A Comparison between Narcolepsy and Depression

Shortened REM latency and increased REM density are frequently observed in both narcolepsy and depression, suggesting a common mechanism of REM sleep disinhibition in these disorders. We compared night sleep recordings of 24 depressive and 24 narcoleptic patients. The amount of REM sleep and REM density did not differ between the patient groups; however, REM latency distributions differed significantly. Whereas in narcoleptic patients REM episodes started either immediately at sleep onset or following at least 60 min of non-REM sleep, in depressives two thirds of REM latencies were in the range from 1 to 60 min. In narcoleptic patients, short as compared to long REM latencies were associated with longer total sleep time, greater sleep efficiency, reduced amounts of wakefulness, and increased amounts of slow-wave sleep. In depressive subjects the reverse pattern was seen. We conclude that a common mechanism of REM sleep disinhibition in narcolepsy and depression is very unlikely.