Effects of sleep deprivation on mood and central amine metabolism in depressed patients.

Nineteen patients, each hospitalized with a major depressive episode, were deprived of sleep for one night. Ten patients responded with clear improvement in depressive symptoms; the substantial clinical change was transient, usually lasting one day. Those who responded had significantly higher initial depression ratings (P less than .01) and tended to be older than nonresponders who experienced mild increases in irritability, fatigue, and discomfort following sleep deprivation. Amine metabolites, 5-hydroxyindoleacetic acid (5HIAA), and homovanillic acid (HVA) were not substantially affected by sleep deprivation, although there was a significant interaction of clinical response and direction of 3-methoxy-4-hydroxyphenylglycol (MHPG) change. Sleep deprivation thus produces acute, but only transient improvement in a selected group of severely depressed patients; it appears to be an important tool in the study of the affective disorders.     

Impact of sleep deprivation and subsequent recovery sleep on cortisol in unmedicated depressed patients

OBJECTIVE: One night of sleep deprivation induces a transient improvement in about 60% of depressed patients. Since depression is associated with abnormalities of the hypothalamic-pituitary-adrenal (HPA) axis, the authors measured cortisol secretion before, during, and after therapeutic sleep deprivation for 1 night. METHOD: Fifteen unmedicated depressed inpatients participated in a combined polysomnographic and endocrine study. Blood was sampled at 30-minute intervals during 3 consecutive nights before, during, and after sleep deprivation. Saliva samples were collected at 30-minute intervals during the daytime before and after the sleep deprivation night. RESULTS: During the night of sleep deprivation, cortisol levels were significantly higher than at baseline. During the daytime, cortisol levels during the first half of the day were higher than at baseline in the patients who responded to sleep deprivation but not in the nonresponders. During recovery sleep, cortisol secretion returned to baseline values. CONCLUSIONS: This study demonstrated a significant stimulatory effect of 1 night of sleep deprivation on the HPA axis in unmedicated depressed patients. The results suggest that the short-term effects of antidepressant treatments on the HPA axis may differ from their long-term effects. A higher cortisol level after sleep deprivation might transiently improve negative feedback to the hypothalamus or interact with other neurotransmitter systems, thus mediating or contributing to the clinical response. The fast return to baseline values coincides with the short clinical effect.     

Auditory evoked potentials and total sleep deprivation in depressed patients

Cortical auditory evoked potentials (latencies N1 and P2, N1-P2 amplitude, and amplitude/stimulus intensity function) were studied before and after 1 night's total sleep deprivation in 20 drug-free depressed inpatients. Responders to sleep deprivation showed an augmenting pattern on the non-dominant hemisphere and a reducing pattern on the dominant hemisphere. The interhemispheric difference in auditory cortex was also apparent in the group of patients who failed to respond to sleep deprivation, but with values pointing in the opposite direction. The augmenting pattern shown by responders in the nondominant hemisphere may be a predictor of therapeutic response to sleep deprivation and to subsequent treatment with drugs influencing serotonergic pathways.     

Towards a model of mood responses to sleep deprivation in depressed patients

It is hypothesized that in depressed patients diurnal variation in mood (DV) is a daily recurring phenomenon, which fails to achieve expression on all days (showing a random distribution of DVs). From this perspective a meta-analysis was performed on the raw data of earlier presented studies. The effect of total sleep deprivation (TSD) on mood was examined in 14 so-called prototypical patients, showing on three successive days either positive DVs (feeling better in the evening) or inverse DVs. It was hypothesized that under baseline conditions mood follows a monotonous course with switching points at 7 AM and 11 PM and that during the TSD night the 7-AM switch took place earlier. The position of this switch was calculated, assuming that (1) before the switch the curve ran parallel to the nightly baseline curves, and (2) after the switch the curve showed a monotonous change parallel to the daily baseline curves. The best fit between predicted and measured depression after TSD was found for a switch at 3 AM, varying the switching point during the TSD night with hourly intervals. The characteristics based on prototypical patients contributed significantly to the prediction of the morning and the afternoon depression levels after TSD in a group of 53 patients (prototypical and nonprototypical).     

Effect of flumazenil-augmentation on microsleep and mood in depressed patients during partial sleep deprivation

The antidepressive effect of sleep deprivation (SD) in depressed patients disappears after sleep of the recovery night and after early morning naps. Both can provoke a rapid relapse into depression in SD-responders. In addition, the occurrence of short episodes of sleep (termed microsleep, MS) during partial SD (PSD) is associated with SD-nonresponse, suggesting that MS during the time awake may be related to relapse or PSD-nonresponse. The GABA-benzodiazepine receptor antagonist flumazenil augments vigilance and reduces NonREM-sleep pressure in early morning recovery sleep in volunteers after SD. Therefore, in this study 27 patients with major depression were subjected to a PSD. In a double blind randomized design either flumazenil or placebo was orally applied during PSD in order to examine whether the application of flumazenil reduces sleep propensity and thus, increases antidepressant efficacy of PSD. EEG was registered continuously for 60h by a portable device for the assessment of microsleep episodes at baseline and during PSD. Flumazenil application significantly suppressed frequency and total amount of MS. While the antidepressant efficacy of PSD was not different between flumazenil and placebo during PSD, the subjective mood improved after the recovery night in patients treated with flumazenil. It is concluded that GABAergic mechanisms are involved in the regulation of MS during PSD, which may be related to a mood stabilizing effect after the recovery night. However, the mechanisms underlying the association between the occurrence of MS during PSD and mood variation have to be further clarified.     

Effects of brief naps on mood and sleep in sleep-deprived depressed patients

To determine the effects of brief naps on mood and electroencephalographic (EEG) sleep in sleep-deprived depressed patients, data from 19 hospitalized patients with depression were analyzed; all were kept awake from 0700h until the following day, when they were allowed 10-min naps at either 0830h or 1500h. Six of the patients showed a clinically significant improvement (greater than 40% change) on the Hamilton Rating Scale for Depression (HRSD) before the nap after all-night sleep deprivation, and the group as a whole showed a significant improvement on the HRSD, the Profile of Mood States, and the Brief Psychiatric Rating Scale subscale for depression. Naps did not alter mood in the responders, but did improve measured depression on the HRSD in the non-responders. Morning and afternoon naps did not differ significantly in their effects on mood or nap sleep. On the recovery sleep, patients who were classified as responders after the nap showed a significantly greater increase in delta (Stage 3 + 4) sleep compared with baseline than nonresponders.     

Dimensions of self-rated mood in depressed, manic, and normal subjects

Self-rated scales allow the comparison of subjective mood across the spectrum of manic, depressive, and euthymic states. This study examined the self-reported mood of manic, depressed, and normal subjects using a 23-item research instrument based on the Carroll-Klein model of bipolar disorder. The Multiple Visual Analog Scale (MVAS) measures the following dimensions: consummatory reward (seven items), incentive reward (two items), psychomotor speed (seven items), and central pain (seven items). The MVAS was completed by 31 manic inpatients, 43 depressed inpatients, and 29 normal volunteer subjects. Total scores, average item scores, and total dimension scores were obtained. Subjects also completed a global mood VAS and the Carroll Depression Scale (CDS). Groups were compared by analysis of variance (ANOVA) and post hoc Bonferroni-Dunn methods. In a separate post hoc analysis, the group of manic patients was divided at the median CDS score into "pure" and "dysphoric" manic subgroups. We found excellent congruence of average 23-item total MVAS scores with global VAS and CDS scores. Dimension scores on the MVAS conformed to the predictions of the Carroll-Klein model. Depressed patients differed significantly from both manic and normal subjects on each dimension. MVAS dimension scores of normal subjects did not differ significantly from those of manic patients. On the dimension of central pain, normal subjects had significantly less inhibited scores than the "pure" subgroup of manics. The results confirmed that the dimensions of the Carroll-Klein model are bipolar and orthogonal. By the MVAS technique, the self-reported mood of normal subjects is similar to the self-reported mood of manic patients on all dimensions of the Carroll-Klein model of bipolar disorder. The positive scores of both groups are clearly distinguished from the negative scores of depressed patients. Average MVAS scores of normal subjects approximated the conventional zero score only on the dimension of central pain. Normal subjects exhibit megalothymic (hyperthymia) on most dimensions of subjective mood. The negative MVAS scores of depressed patients are even more deviant from normal than the conventional scoring system would suggest.     

The effect of sleep deprivation on depressed patients.

In this paper an account is given of the effect of single-night sleep deprivation (SD) therapy in 124 depressive patients of different diagnostic groups. Phasic depressives showed a marked improvement after treatment by sleep deprivation. Because these improvements were often of short duration, we repeated the treatments and combined them with thymoleptic drugs. In the group of neurotic depressives the therapeutic effect of sleep deprivation varied; on the whole, however, the improvement was less marked. It is pointed out that the vital symptoms and "critical time" are of importance. Sleep deprivation can be explained as a resynchronization of disturbed circadian rhythms brought about by interrupting these rhythms.     

Effect of acute total sleep deprivation on plasma melatonin,cortisol and metabolite rhythms in females

Disruption to sleep and circadian rhythms can impact on metabolism. The study aimed to investigate the effect of acute sleep deprivation on plasma melatonin, cortisol and metabolites, to increase understanding of the metabolic pathways involved in sleep/wake regulation processes. Twelve healthy young female participants remained in controlled laboratory conditions for ~92 hr with respect to posture, meals and environmental light (18:00–23:00 hr and 07:00‐09:00 hr <8 lux; 23:00–07:00 hr 0 lux (sleep opportunity) or <8 lux (continuous wakefulness); 09:00–18:00 hr ~90 lux). Regular blood samples were collected for 70 hr for plasma melatonin and cortisol, and targeted liquid chromatography–mass spectrometry metabolomics. Timepoints between 00:00 and 06:00 hr for day 1 (baseline sleep), day 2 (sleep deprivation) and day 3 (recovery sleep) were analysed. Cosinor analysis and MetaCycle analysis were performed for detection of rhythmicity. Night‐time melatonin levels were significantly increased during sleep deprivation and returned to baseline levels during recovery sleep. No significant differences were observed in cortisol levels. Of 130 plasma metabolites quantified, 41 metabolites were significantly altered across the study nights, with the majority decreasing during sleep deprivation, most notably phosphatidylcholines. In cosinor analysis, 58 metabolites maintained their rhythmicity across the study days, with the majority showing a phase advance during acute sleep deprivation. This observation differs to that previously reported for males. Our study is the first of metabolic profiling in females during sleep deprivation and recovery sleep, and offers a novel view of human sleep/wake regulation and sex differences.     

Motor activity in depressed patients during therapeutic sleep deprivation

ProblemBoth sleep and motor activity have a bidirectional relationship with depression. The existing literature on motor activity during therapeutic sleep deprivation in depressed patients is inconsistent and fragmentary. In the present study we measured motor activity continuously during 40 hours of sleep deprivation in depressed patients.MethodThirty-four inpatients suffering from a major depression (DSM-IV) underwent sleep deprivation with a continuous waking period of 40 hours. Motor activity of the patients was continuously recorded using an actigraph on the non-dominant wrist. The effect of sleep deprivation was assessed by the Hamilton Depression Scale (six-item version), thus separating the group into responders and non-responders to sleep deprivation.ResultsWe found no significant differences in motor activity between responders and non-responders on the day before sleep deprivation. During the night, responders to sleep deprivation exhibited a higher motor activity and less periods of rest. On the day after sleep deprivation, responders exhibited a higher activity, too.ConclusionsMotor activity levels differ between the two groups, thus giving more insight into possible mechanisms of action of the therapeutic sleep deprivation. We suggest that higher motor activity during the night prevents naps and leads to better response to sleep deprivation.     

Influence of mirtazapine on urinary free cortisol excretion in depressed patients

Mirtazapine has been shown to acutely inhibit cortisol secretion in healthy subjects. In the present study, the impact of mirtazapine treatment on urinary free cortisol (UFC) excretion was investigated in depression. Twenty patients (six men, 14 women) suffering from major depression according to DSM-IV criteria were treated with mirtazapine for 3 weeks. The patients received 15 mg mirtazapine on day 0; 30 mg mirtazapine on day 1; and 45 mg mirtazapine per day from day 2 to the end of the study (day 21). UFC excretion was measured before treatment (day 1), at the beginning (day 0), after 1 week (day 7) and after 3 weeks (day 21) of treatment with mirtazapine. Urine samples were collected from 08:00 to 08:00 h the following day. On the days of urine sampling, the severity of depressive symptoms was assessed using the 21-item version of the Hamilton Rating Scale for Depression (21-HAMD). There was a significant reduction of UFC excretion during 3-week mirtazapine therapy, which was already obvious after the first day of treatment (day 0). However, there were no significant across-subjects correlations between UFC reduction and decrease in 21-HAMD sum scores. Apparently, the mirtazapine-induced rapid reduction of cortisol secretion in depressed patients is not necessarily correlated with a favorable therapeutic response.     

Effects of one night's sleep deprivation on mood and behavior in panic disorder. Patients with panic disorder compared with depressed patients and normal controls

The effects of one night's sleep deprivation on mood and behavior were evaluated in 12 patients with panic disorder, ten depressed patients, and ten controls. In contrast to the improvement in symptoms of anxiety and depression shown by the majority of depressed patients, the response of patients with panic disorder as a group did not differ from that of normal controls, although a subgroup did experience noticeable worsening in their symptoms of anxiety, with 40% experiencing panic attacks on the day following sleep deprivation. Electroencephalographic recordings with nasopharyngeal electrodes on the day following sleep deprivation were normal, further suggesting that patients with panic disorder do not have seizure activity characteristic of temporal lobe epilepsy.     

Relationship of response to sleep deprivation and carbamazepine in depressed patients

The responses of 16 patients with major depressive disorder to one night's sleep deprivation and a subsequent double-blind, placebo-controlled trial of carbamazepine were compared. There was a significant association between the presence or absence of an antidepressant response to each of these treatments. Further studies are required to assess the clinical utility of this relationship and whether it is based on antidepressant response to any agent or is more specific to carbamazepine.     

全部睡眠剥夺对健康男性青年情绪的影响

目的 探讨长时间睡眠剥夺（SD）对情绪的影响。方法 挑选身体健康男性青年志愿者30名,剥夺全部睡眠52h。采用情绪状态问卷、贝克焦虑问卷、考虑自评量表、状态焦虑问卷和自评抑郁量表,分别在SD前（基础值）、SD期间（1次／6h,共8次）及一夜恢复性睡眠后评定受试者的情绪状态。结果 与基础值比较,随SD时间的延长,疲惫－惰性、焦虑、抑郁、困惑-迷茫等消极情绪的因子分逐渐增加（P＜0．05－0．001）,并与SD时间呈正相关;而有力－好动积极情绪因子分逐渐下降（P＜0．001）,与SD时间呈负相关（r＝－0．846,P＜0．001）。一夜恢复性睡眠后,疲惫－惰性和有力－好动因子分与基础值的差异仍有显著性（P＜0．05－0．01）,余均恢复到基础水平。结论 长时间的SD可导致情绪逐渐恶化。;一夜的恢复性睡眠对情绪的改善有一定效果。     

Effect of sleep deprivation on brain metabolism of depressed patients.

OBJECTIVE: Sleep deprivation is a rapid, nonpharmacologic antidepressant intervention that is effective for a subset of depressed patients. The objective of this study was to identify which brain structures' activity differentiates responders from nonresponders and to study how metabolism in these brain regions changes with mood. METHOD: Regional cerebral glucose metabolism was assessed by positron emission tomography (PET) with [18F]deoxyglucose (FDG) before and after total sleep deprivation in 15 unmedicated awake patients with unipolar major depression and 15 normal control subjects, who did the continuous performance test during FDG uptake. RESULTS: After sleep deprivation, four patients showed a 40% or more improvement on the Hamilton Rating Scale for Depression. Before sleep deprivation the depressed responders had a significantly higher cingulate cortex metabolic rate than the depressed nonresponders, and this normalized after sleep deprivation. The normal control subjects and nonresponding depressed patients showed no change in cingulate metabolic rate after sleep deprivation. CONCLUSIONS: Overactivation of the limbic system as assessed by PET scans may characterize a subset of depressed patients. Normalization of activity with sleep deprivation is associated with a decrease in depression.     

Modafinil reduces microsleep during partial sleep deprivation in depressed patients

Objective

Sleep deprivation (SD) can induce a prompt decrease in depressive symptoms within 24 h. Following the recovery night, however, a relapse into depression occurs in most patients. Recovery sleep, naps and even very short episodes of sleep (microsleep; MS) during SD have been shown to provoke a rapid relapse into depression. This study tested the hypothesis that modafinil reduces MS during SD and stabilizes the treatment response to PSD compared to placebo.

Methods

A total of 28 patients (13 men, 15 women; age 45.1 ± 12.1 years) with a major depressive episode and a cumulative daytime microsleep of five or more minutes were investigated using a double-blind placebo-controlled study design. All patients were treated with a stable mirtazapine monotherapy. A partial SD (PSD) was performed after one week. Additional morning treatment with modafinil vs. placebo started during PSD and was maintained over two weeks. Sleep-EEG and MS episodes were recorded with a portable EEG. Depression severity was assessed using the Hamilton Depression Rating Scale before, during and after PSD and at follow-ups after one and two weeks.

Results

Patients treated with modafinil showed significantly reduced microsleep during PSD (11.63 ± 15.99 min) compared to the placebo group (47.77 ± 65.31 min). This suppression of MS was not associated with the antidepressive effect of PSD.

Conclusions

Compared to placebo, modafinil was efficient in reducing daytime microsleep following partial sleep deprivation but did not enhance the antidepressive effects of PSD and did not stabilize antidepressive effects over two weeks.     

The effects of amineptine on the mood and nocturnal sleep of depressed patients

The effect of amineptine, a new tricyclic antidepressant, was studied on the sleep of 12 depressed patients. A single blind comparative trial vs placebo was carried out and changes in depression symptoms were recorded using Hamilton Rating Scale for Depression (HRSD). The sleep was evaluated according to the Rechtschaffen and Kales criteria to determine various parameters. Amineptine treatment induced statistically significant reduction of HRSD total score after 14 days of treatment. Polysomnographic analysis revealed significant differences between depressed patients and healthy volunteers.