Reduced REM Latency Research Articles

P006 Case study: Dancing eyes post COVID-19 vaccination

Abstract INTRODUCTION We describe a case of rapid eye movements in NREM sleep in a patient who had Guillain-Barre Syndrome (GBS) post AstraZeneca ( AZ) COVID-19 vaccine. This has not been reported previously. METHOD An 81-year-old male with recent diagnosis of GBS secondary to AZ COVID-19 vaccination was referred of investigation of sleep disordered breathing. A Level 2 PSG showed rapid eye movements in the absence of atonia predominantly during N1 sleep. A second study one month later confirmed the persistence of the eye movements. RESULTS Study 1 revealed mild supine and REM-predominant obstructive sleep apnoea (AHI = 14.9/hr) with reduced REM latency (44.5 minutes) & slow wave sleep (1.6%). Study 2 showed normal REM latency (61.5 minutes). REM indices were 0.33 per minute of N1 sleep and 0.12 for N2 sleep. REM density was 3% during N1 and 0.55% in N2. DISCUSSION COVID-19 vaccinations have been associated with various side-effects, some of which have been attributed to autoimmune response. A previous study on GBS patients reported sleep architecture abnormalities including sleep onset REM periods and abnormal eye movements in NREM sleep, during acute phase attributed to autonomic dysfunction and transitory hypocretin-1 transmission reduction . Our patient had almost completely recovered from GBS when we performed Study 1. We believe this to be the first case of abnormal eye movements in sleep being identified on polysomnography in a patient with GBS following AZ Covid-19 vaccination

Effects of suvorexant on sleep architecture and power spectral profile in patients with insomnia: analysis of pooled phase 3 data

BackgroundThe orexin receptor antagonist, suvorexant, is approved for treating insomnia at a maximum dose of 20 mg. We evaluated its effects on sleep architecture. MethodsThe analyses included pooled polysomnography data from two similar randomized, double-blind, placebo-controlled, 3-month trials evaluating two age-adjusted (non-elderly/elderly) dose regimes of 20/15 mg and 40/30 mg in 1482 patients with insomnia. Polysomnography was recorded at baseline and on three nights during the treatment: Night-1, Month-1, and Month-3. Effects on non-REM sleep stages 1 (N1), 2 (N2), 3 (N3)/slow wave sleep (SWS), and REM sleep were evaluated. A power spectral analysis of non-REM sleep was also performed. ResultsSuvorexant increased the time (in minutes) spent in all sleep stages compared with placebo. When suvorexant and placebo were compared in terms of changes in percentage of total sleep time spent in each stage, there were small decreases of ≤1%, ≤2.2%, and ≤0.8% for N1, N2, and N3/SWS on average, respectively, and an average increase of ≤3.9% in REM. The largest differences from placebo were observed at Night-1 and generally diminished over time. Suvorexant reduced REM latency (number of non-REM 30-s epochs from lights-off to the first REM epoch) compared with placebo; the reduction was greater at Night-1 (~40–50 non-REM epochs) in comparison to later time points (~12–25 non-REM epochs at Month-3). The spectral analysis of non-REM showed a small decrease in power of 3–6% in the gamma and beta bands, and a small increase of 4–8% in the delta band, at Night-1 for suvorexant relative to placebo; these effects were not apparent at the later Month-1 and Month-3 time points. ConclusionOverall sleep architecture appears to be preserved in insomnia patients taking suvorexant. The power spectral profile of suvorexant is generally similar to placebo.

Sleep and dreaming in patients with borderline personality disorder: A polysomnographic study

Previous research has demonstrated disturbances in sleep continuity in subjects with borderline personality disorders (BPD). Moreover, depression-like sleep abnormalities like reduced REM latency have been found in BPD subjects, even without comorbid major depression disorder. Yet it is still unknown what the effect is of co-morbid posttraumatic stress disorder on sleep continuity and dream content in BPD patients group. The present study compared 27 unmedicated female BPD subjects and healthy controls. The patients exhibited increased sleep fragmentation, increased REM density, and reduced REM latency. The findings were independent from co-morbid posttraumatic stress response (PTSD), which was present in 33% of the patient sample. Negatively toned dreams obtained by REM awakenings and nightmares were also reported more often by the patients—also irrespective of co-morbid PTSD—whereas dreams of specific BPD behavior, like self-mutilation, were rare. Taking these finding into account, one might productively investigate whether the sleep abnormalities improve during successful treatment of BPD and whether efficient methods for treating nightmares can be beneficial for this patient group.

Peeking into the minds of troubled adolescents: The utility of polysomnography sleep studies in an inpatient psychiatric unit

Sleep problems are commonly associated with the primary diagnostic criteria for many psychiatric disorders. Evidence suggests sleep disturbances may precede development of psychiatric disorders and the severity of psychopathology reflects the severity of sleep problems. Polysomnography (PSG) sleep studies in child and adolescent psychiatric populations, a particularly at risk group, has considerable value but has been more elusive requiring further investigation. We performed a retrospective chart review of PSG sleep studies and psychiatrist evaluations of 106 adolescents aged 7-16 admitted to an involuntary adolescent psychiatric inpatient facility. Less than 5% of cases had mild/no sleep problems. Hyperarousal hallmarked this population, and severity of sleep disturbances trends with the severity of psychopathology. Inpatients with multiple psychiatric disorders had greater frequencies of insomnia, decreased sleep efficiency, and arousals from SWS (p<0.05). Inpatient's with self-harm behavior more frequently had elevated sleep onset latency (SOL), reduced efficiency, reduced SWS (p<0.05), increased REM, and reduced REM latency compared to inpatients with dysthymia and/or depression. Lacking an a priori hypothesis, this study was explorative and uncontrolled for factors such as medications. This notwithstanding however, analysis indicates the majority of inpatients were taking cocktails that "should" alleviate sleep symptoms suggesting greater associations may prevail in unmedicated populations. This study attests to the potential clinical utility of PSG sleep studies in the management of adolescent psychiatric disorders and contributes to the body of evidence reputing the intimate connection between sleep problems and the development and perpetuation of psychopathology with public health implications.

Heterogeneity in EEG sleep findings in adolescent depression: unipolar versus bipolar clinical course

Background: EEG sleep measures in child and adolescent subjects with depression have shown considerable variability regarding group differences between depressed and control subjects. This investigation was designed to assess whether some of the observed variability is related to undifferentiated unipolar and bipolar disorders in a sample that was reported previously. Methods: Twenty-eight adolescents who met criteria for unipolar major depression and 35 controls with no lifetime psychiatric disorder participated in a cross-sectional sleep polysomnography study. Approximately 7 years later, follow-up clinical evaluations were conducted in 94% of the original cohort. Clinical course during the interval period was assessed without knowledge of subjects’ initial diagnostic and psychobiological status. Re-analysis of the original sleep data were performed with the added information of longitudinal clinical course. Results: Depressed subjects who had a unipolar course showed reduced REM latency, higher REM density, and more REM sleep (specifically in the early part of the night) compared with depressed adolescents who converted to bipolar disorder and controls who remained free from psychopathology at follow-up. In contrast to the unipolar group, depressed subjects who would later switch to bipolar disorder had demonstrated more stage 1 sleep and diminished stage 4 sleep. Conclusions: These preliminary results indicate that some of the observed variability in EEG sleep measures in adolescent depression appear to be confounded by latent bipolar illness. The findings also suggest that sleep regulatory changes associated with unipolar versus bipolar mood disorders may be different.

REM sleep and prolactin in patients with non-affective psychoses

Reduced REM latency is a common polysomnographic finding in patients with schizophrenia. This has been attributed to cholinergic hyperactivity secondary to increased dopaminergic tone. We studied polysomnographic sleep recordings, and morning serum prolactin levels as a measure of dopaminergic tone in 17 drug-free patients suffering from non-affective psychoses, hypothesizing that REM-latency and prolactin would correlate. A clear-cut positive correlation between prolactin and REM latency was found, as well as a negative correlation between prolactin and REM sleep. The findings may be explained by dopaminergic and secondary hypercholinergic and/or serotonergic mechanisms responsible for the regulation of REM sleep and the secretion of prolactin.

REM sleep and prolactin in patients with non-affective psychoses

Reduced REM latency is a common polysomnographic finding in patients with schizophrenia. This has been attributed to cholinergic hyperactivity secondary to increased dopaminergic tone. We studied polysomnographic sleep recordings, and morning serum prolactin levels as a measure of dopaminergic tone in 17 drug-free patients suffering from non-affective psychoses, hypothesizing that REM-latency and prolactin would correlate. A clear-cut positive correlation between prolactin and REM latency was found, as well as a negative correlation between prolactin and REM sleep. The findings may be explained by dopaminergic and secondary hypercholinergic and/or serotonergic mechanisms responsible for the regulation of REM sleep and the secretion of prolactin.

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 …

Dexamethasone response, thyrotropin-releasing hormone stimulation, rapid eye movement latency, and subtypes of depression

Most prior studies of mood disorders have used a single laboratory test to assist in differential diagnosis, prediction of treatment response, and prediction of relapse. This study compared three laboratory measures in a combined in- and outpatient sample of depressed patients. Dexamethasone suppression test (DST) nonsuppression occurred in 46% of patients with endogenous major depression, in 15% with nonendogenous major depression, and in 56% with bipolar, depressed phase disorder. A blunted thyrotropin-releasing hormone stimulation test (TRH-ST) occurred in 25% of patients with endogenous, 10% with nonendogenous, and 44% with bipolar, depressed phase disorder. Reduced REM latency was found in 65% of endogenous major depressions, in 34% of nonendogenous major depressions, and in 53% of bipolar, depressed phase disorders. Fifty-one percent of those with reduced REM latency also evidenced DST nonsuppression. When the endogenous major depression and bipolar, depressed phase groups were combined, 28% had no laboratory abnormality, whereas 8% evidenced all three. These findings suggest that 1) endogenous/nonendogenous unipolar groups are distinguished by all three laboratory tests; 2) most patients with a blunted TRH-ST also evidence DST nonsuppression; and 3) one half of patients with reduced REM latency evidence DST nonsuppression. Sensitivity is greatest and specificity is lowest for REM latency, followed by the DST and then the TRH-ST.

Identifying an abnormal electroencephalographic sleep profile to characterize major depressive disorder

There is little agreement as to the best definition of a categorically abnormal electroencephalographic (EEG) sleep profile to characterize major depressive disorder. Therefore, a series of classification, replication, and validation analyses were conducted to identify such a profile. The EEG sleep studies of healthy controls (n = 44), depressed inpatients (n = 44), and depressed outpatients (n = 181) were utilized, including subgroups of patients studied both before and after nonpharmacologic treatment with either cognitive behavior therapy (CBT) or interpersonal psychotherapy (IPT). A discriminant index score (based on reduced REM latency, increased REM density, and decreased sleep efficiency) was found to: 1) reliably discriminate between depressed inpatients, depressed outpatients, and controls; 2) show good test-retest reliability; and 3) identify a subset of depressed outpatients who were older, manifested a broader array of EEG sleep disturbances, and were less responsive to CBT or IPT. Posttreatment studies of patients indicated that normal sleep profiles were relatively stable, whereas abnormal profiles tended to normalize. These findings provide an empirically validated method that may improve the applicability, efficiency, and prognostic utility of EEG sleep studies of depressed patients.

Stressful life events and EEG sleep in depressed and normal control adolescents

EEG sleep measures in 35 depressed and 33 normal control adolescents were examined in relation to stressful life events occurring in the year before sleep studies. There was a significant interaction between stressful life events and diagnostic status for REM latency and total REM time. In the normal controls, the presence of stressful life events was significantly associated with reduced REM latency and increased total REM time. Among the depressed adolescents, there were no significant effects of stressful life events on REM latency or total REM time. The depressed adolescents with no stressful life events (n = 9) had significantly lower REM latency values compared to normal control adolescents with no stressful life events (n = 13)(61.7 +/- 50.0 vs. 132.1 +/- 79.0, p < or = .01). It appears that stressful life events influence at least some measures of adolescent sleep and should be considered in future controlled studies aimed at understanding sleep changes in adolescent depression.

Effects of race on EEG sleep in major depression

The constellation of EEG sleep changes observed in unipolar depression includes reduced REM latency, increased REM time, increased phasic REM activity, and slow-wave sleep deficits. Effects of depressive severity, medication, family history, episode history, sleep schedules, season, reproductive phase, age, and sex on these measures have been characterized with varying precision. One influence that is virtually uneharacterized is race. Data from an epidemiologically representative sample indicate that races differ with regard to prevalence of affective disorders, with African-Americans at reduced risk relative to Euro-Americans. Studies implicating EEG sleep abnormalities in vulnerability for onset and recurrence of depression indicate that effects of race must be understood. To evaluate the effects of race on sleep, we have conducted a retrospective study of unipolar depressed patients who had participated in research protocols at Western Psychiatric Institute and Clinic from 1981-1994. Groups were based on self-described race (black/white) and were matched blind to EEG sleep data within research protocol to control for diagnostic practices, age, and sex. Patients with histories of substance abuse, alcohol abuse, psychotic disorders, and bipolar disorders were excluded. Only patients with at least two consecutive nights of EEG sleep were included. To date, 46 African-American unipolar depressed patients have been matched to 90 age-, sex-, and protocol-matched Euro-Americans. A double-matched control group was generated to reduce error variance and increase power to detect differences. Results will be discussed with regard to an array of vulnerability factors for unipolar depression.

Polysomnographic studies of unmedicated depressed men before and after cognitive behavioral therapy

Differentiation of stable, trait-like characteristics from more episodic or state-dependent disturbances will be helpful in gaining a better understanding of the pathophysiology of depression. However, research in this area has been complicated by artifactual and clinical problems associated with pharmacologic treatment. In this investigation the authors used EEG sleep studies to assess medication-free depressed male patients before and after cognitive behavioral therapy. Forty-five male patients with the diagnosis of major depression according to the DSM-III-R criteria and the Research Diagnostic Criteria underwent EEG sleep studies before and after 16 weeks of cognitive behavioral therapy, during which they were free of medication. In addition to the documentation of changes within these patients, the findings were compared with those for 47 healthy subjects, including 15 who were restudied 12-24 months after their baseline assessments. The EEG sleep profiles of the depressed patients showed a significant reduction in REM sleep density after treatment, suggesting "normalization" of an abnormal state-dependent process. By contrast, slow wave sleep and tonic REM measures, including reduced REM latency, were unchanged after treatment. These findings suggest that early in remission there is disaggregation of irreversible, trait-like correlates of depression (e.g., diminished slow wave sleep and reduced REM latency) from more reversible disturbances (e.g., increased REM density).

Conversion Disorder Revisited: Severe Parasomnia Discovered

In light of recently described and reviewed disorders of movement and behaviour during sleep, the long standing diagnosis of conversion disorder in a forty-nine year old Vietnam veteran was reappraised. Polysomnographic studies showed that the nocturnal component of his "pseudoseizures" was due to physical disorder, a severe mixed parasomnia comprising the recently described REM behaviour disorder and a non-REM parasomnia. His sleep architecture was also deranged, featuring reduced REM latency and increased REM density. An association between these abnormalities and psychological trauma is recognised in the literature. Treatment with clonazepam has abolished the nocturnal behavioural disturbance. His daytime pseudoseizures occur less frequently and his general well being is improved. The case is a reminder that physical disorder may underlie and act as prototype to the psychologically-driven symptom. Before attributing behavioural disturbance at night to psychological causes alone, polysomnographic studies should be done to exclude a treatable parasomnia.

Sleep, excessive daytime sleepiness and fatigue in Parkinson's disease.

The objective of this questionnaire-based survey was to evaluate the prevalence and causes of sleep disturbances in 90 nondepressive patients with Parkinson's disease (PD) and 71 age-matched healthy subjects. We also assessed the prevalence and characteristics of excessive daytime sleepiness (both groups) and excessive fatigue (PD patients). A high prevalence of sleep disturbances in PD patients was found; this is to a large extent probably the result of aging. As compared with controls, patients had a more severely disturbed sleep maintenance because of nycturia, pain, stiffness, and problems with turning in bed. The prevalence of excessive dreaming is similar in both groups, but altered dream experiences almost exclusively occurred in PD. Patients rated themselves more often to be morning-types than controls. This finding may account for the reported adaptation effects in experimental settings and the reduced REM latency in PD patients. The prevalence of daytime sleepiness was similar in both groups. Excessive daytime sleepiness showed a clear diurnal pattern with a peak in the early afternoon. As for excessive fatigue, the majority of the patients did not report a preferential time for this symptom. Our findings further argue against an association of fatigue with any circadian factor, and instead suggest a relationship with the motor deficits of PD.

Social factors and the psychobiology of depression: Relations between life stress and rapid eye movement sleep latency.

We examined psychosocial factors (i.e., life stress) and biological factors (i.e., REM sleep latency) that are hypothesized to be of complementary importance for defining depressive subtypes in a sample of 61 nonpsychotic, endogenous major depressives. Subjects were evaluated on several diagnostic scales for life stress, on electroencephalographic sleep data, and on 2 symptom measures for depression. As predicted, persons with severe stress that occurred shortly before depression onset had essentially normal REM latency values; patients without such stress had reduced REM latency values. Both stress and REM latency were also associated with greater severity of self-reported depressive symptoms. Alternative explanations of these findings are discussed, with particular emphasis on different roles of pre-onset and post-onset stressors.

Electroencephalographic sleep measures in prepubertal depression

Two nights of electroencephalographic (EEG) sleep recording were performed in a group of prepubertal subjects with major depressive disorder (MDD) ( n = 36, mean age = 10.4, SD = 1.5) and age-matched normal control children ( n = 18, mean age = 10.1, SD = 1.6). All subjects were medically healthy and free of medications at the time of the study. There were no significant group differences for any major sleep variable after the initial adaptation night in this study. One subgroup of MDD subjects ( n = 8) showed reduced REM latency on both recording nights, decreased stage 4 sleep, and increased REM time; this subgroup had significantly higher severity scores for depression but did not otherwise appear to be clinically distinct from the rest of the MDD subjects. Overall, the results indicate that the EEG sleep changes associated with depression in adults occurred less frequently in prepubertal MDD subjects.

Reduced REM Latency in Depression: Mechanical Considerations-Reply

In Reply.— We thank Dr Schwartz for his most interesting letter concerning our report. 1 As we stated there and in an earlier report on social zeitgebers and biologic rhythms, 2 our collaborative work on sleep physiology is embedded in an overall framework of biologic rhythms. We agree that the understanding of depression may very well require an increase in our knowledge base of several biologic rhythms, including sleep. Dr Schwartz suggests that we have confounded several key concepts, which may require some clarification. 1 In short, he has suggested that we have mistakenly related increased REM pressure to decreased REM latency... Perhaps there is a misunderstanding, since if one REM deprives individuals and REM latency shortens during the recovery sleep, a clear relationship exists between REM pressure and decreased REM latency. Dr Schwartz' second criticism is that we have neglected the contributions of the desynchronization data and phase theories of mood

Cognitive behavior therapy of endogenous depression: Part 1: An outpatient clinical replication series

A clinical replication series of 38 patients meeting Research Diagnostic Criteria for probable (n=6) or definite (n=32) endogenous depression (ED) were treated in 16 week, 20 session protocol with cognitive behavior therapy (CBT). Nearly 75% (28/38) of patients met response criteria at the end of the protocol, with robust reductions of symptomatic ratings (p's<0.0001). Contrary to our prediction, patients with reduced rapid eye movement sleep latency (a biological correlate of ED) generally responded as well to CBT as patients with nonreduced values, with reduced REM latency patients showing more rapid improvement on several measures. In the outpatient setting, CBT's spectrum of efficacy clearly appears to extend to ED patients, including those with at least one objective indicator of biological dysfunction.

Reduced REM latency predicts response to tricyclic medication in depressed outpatients

Forty-two outpatients with major depressive disorder entered a double-blind, randomized trial of either desipramine or amitriptyline for a minimum of 6 weeks. Pretreatment polysomnographic and clinical measures were used to predict response. Response was defined as a 17-item Hamilton Rating Scale for Depression score ⩽9 at the end of treatment. There was a 61.1% response rate for patients treated with amitriptyline and a 66.7% response rate for patients treated with desipramine. Reduced REM latency (2-night mean ⩽65.0 min) predicted a positive response to these tricyclic antidepressants. REM latency did not differentiate between desipramine or amitriptyline responders. More patients with reduced REM latency (80%) responded to treatment compared with patients with nonreduced REM latency (50%). The 80% response rate in reduced REM latency depressed patients confirms our previous findings in a mixed inpatient and outpatient sample. Contrary to our hypothesis, in this sample, endogenous depression was not associated with a good response to tricyclic medication.