Sleep deprivation effects in older endogenous depressed patients

In a drug-free group of 15 older endogenous depressed inpatients, all-night sleep deprivation (SD) was associated with a significant decrease in Hamilton depression scores and in Profile of Mood States self-ratings of depression. Six of 15 patients (40%) were responders to SD, as evidenced by greater than or equal to 30% improvement in Hamilton ratings. While symptomatic improvement was short-lived (8 of 15 patients worsened after 1 night of recovery sleep), five patients showed further improvement after 1 night of recovery sleep. The final two patients had an increase in Hamilton ratings after sleep deprivation, with a return to baseline values after 1 night of recovery sleep. Responders (but not nonresponders) showed significant improvement in sleep latency, sleep efficiency, and slow wave sleep during recovery sleep (as did controls). The SD Hamilton depression rating (at 9 a.m. after all-night sleep deprivation) showed a significant inverse correlation with the increase in slow wave sleep (SWS) minutes and in SWS % from baseline to first recovery night. Responders also had significantly larger increases in SWS minutes than did nonresponders (53.8 vs. 7 minutes). Similarly, the % change in Hamilton depression ratings was predicted by baseline Stage 4 sleep. These findings suggest that there is a mutual interaction between the process of sleep regulation and the symptoms of depression. They also confirm a prediction from the two-process model of sleep regulation--namely, that improved sleep initiation and maintenance and increased SWS, attained by SD, are associated with clinical improvement.     

Diagnostic criteria of depressive pseudodementia

Ten patients fulfilling the DSM III (A, B, C, D) criteria for both dementia and major depression and presenting the diagnostic dilemma of depressive pseudodementia were included in a prospective study in search of indices for the differential diagnosis of depressive pseudodementia (DPSD) and organic dementia (OD). Patients were assessed with the Hamilton Depression Rating Scale (HDRS), the Blessed Dementia Rating Scale (BDRS), the Wells's criteria, the Mini Mental State (MMS), computerized tomography (CT scan) of the brain, the dexamethasone suppression test (DST), total plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) and sleep electroencephalograms (EEG). Patients suffering from DPSD were defined as showing an improvement higher than 50% in both the HDRS et BDRS scores following adequate antidepressant treatment. Wells's criteria, MMS scores, CT scan and DST do not contribute to the separation of DPSD (n = 6) and OD (n = 4). On the contrary, plasma MHPG levels higher than 35 ng/ml and EEG measures of sleep structure and REM sleep significantly differentiate the two groups.     

Rapid eye movement sleep deprivation as a probe in elderly subjects

The effects of a 2-night rapid eye movement (REM) sleep deprivation (RSD) procedure on electroencephalographic sleep and mood were examined in 15 healthy elderly control subjects, 14 elderly patients with endogenous depression, and 15 patients with primary degenerative dementia. Compared with control subjects, both patient groups maintained a higher amount of REM sleep time and REM activity during RSD. Unexpectedly, depressed patients showed little rebound in visually scored or automated REM sleep measures following RSD, and they showed stability of REM activity temporal distribution from baseline to recovery conditions. This contrasted with the rebound in REM sleep activity seen in control subjects, and the more modest increase in demented patients. The RSD was fairly specific, with some impact on delta sleep during the procedure but not during recovery sleep. Mood ratings were unaffected by RSD. These findings demonstrated a greater plasticity of REM sleep regulation in the healthy elderly control subjects and suggested a higher REM "pressure" with a "ceiling effect" in depressed patients. Patients with dementia appeared to have an impaired capacity to respond to the challenge of RSD.     

Effects of partial sleep deprivation on the diurnal variation of mood and motor activity in major depression.

Partial sleep deprivation (PSD), keeping a subject awake from 2 AM to 9 PM produces an acute mood improvement in 60% of patients with major depression. We sought to characterize the timing, subcomponent mood, and motor activity changes of this response. Thirty-seven subjects with major depression were rated with the 6-item Hamilton Depression Scale (HAM-6) at 1 PM and completed the Profile of Mood States (POMS) every 2 hr on the day before and day of PSD. Locomotor activity was monitored continuously during the trial with an automated device. Bipolar I patients responded more frequently than other groups. Positive mood responders had greater improvement than nonresponders in POMS subscales of depression, tension, confusion, and anger. The mood improvement increased steadily during the day, peaked in late afternoon, and declined thereafter. Responders showed significantly higher levels of locomotor activity on the baseline pre-PSD day than did nonresponders. All subjects increased motor activity following sleep deprivation, however.     

Reliable discrimination of elderly depressed and demented patients by electroencephalographic sleep data

Using electroencephalographic sleep data from a sample of 235 elderly subjects, discriminant function analyses of sleep alterations in depression and dementia were performed. Overall, 80% of patients were correctly classified using a backward discriminant function analysis, and 81% with a general stepwise discriminant function analysis. Four measures contributed to the separation of depressed and demented patients: rapid eye movement (REM) sleep latency (lower in depressives); REM sleep percent (higher in depressives); indeterminate non-REM sleep percent (higher in demented patients, reflecting greater loss of spindles and K complexes); and early morning awakening (more marked in depressives). When both discriminant functions were subjected to cross-validation in independent subsamples, both procedures correctly identified 78% of patients. The classification functions derived from nondemented depressed and nondepressed demented patients were applied to a mixed-symptom group (n = 42). Overall, 27 patients (64%) with either depressive pseudodementia or dementia with depressive features were correctly classified using the same four predictor variables. These findings suggest that sleep physiological alterations of depression and dementia reflect between-group differences in sleep continuity, sleep architecture, and REM sleep temporal distribution, and that the differences are statistically reliable, in both diagnostically pure and mixed clinical presentations. These findings are discussed in the context of current hypotheses of sleep regulation and its mechanisms.     

Electroencephalographic sleep in late-life neuropsychiatric disorders

Late-life depression and dementia of the Alzheimer's type both have profound, although different, effects on electroencephalographic (EEG) sleep patterns. Thus, while depression is associated with REM sleep disinhibition and extreme sleep fragmentation (e.g., sleep onset REM periods and early morning awakenings), Alzheimer's disease is associated with deficits in the production of phasic activity during sleep (e.g., rapid eye movements and K-complexes) and with increased rates of sleep-disordered breathing. These differences have been shown to be reliable in large numbers of patients during the past five years and appear to extend to differences in sleep between depressive pseudodementia and dementia with secondary depression. Preliminary data also suggest that pretreatment sleep onset REM periods may be associated with enhanced vulnerability to recurrent depression. In summary, sleep physiological measures provide useful diagnostic and prognostic indexes in late-life neuropsychiatric disorders.     

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.     

Bedside differentiation of depressive pseudodementia from dementia

The authors analyzed the pretreatment clinical presentations of 14 patients with depressive pseudodementia and 28 patients with primary degenerative dementia as measured by the Mini-Mental State, the Blessed Dementia Rating Scale, and the Hamilton Rating Scale for Depression. They found that patients with pseudodementia showed significantly greater pretreatment early morning awakening, higher ratings of psychological anxiety, and more severe impairment of libido. Patients with dementia, however, showed significantly more disorientation to time, greater difficulty finding their way about familiar streets or indoors, and more impairment with dressing. The authors suggest that these findings be considered preliminary.     

抑郁症相关性失眠的临床特征与多导睡眠图研究

目的探讨抑郁症相关性失眠症状的临床特征与抑郁症睡眠的结构特征。方法对符合抑郁症诊断标准,且具有明显失眠症状的患者71例,进行了汉密尔顿抑郁量表、汉密尔顿焦虑量表、匹兹堡睡眠质量指数评定,以及整夜多导睡眠监测,并随机选取30例正常人作为对照组。结果抑郁症相关性失眠患者相对于对照组,睡眠症状方面表现出睡眠潜伏期长、维持时间短、睡眠效率低、睡眠质量差、日间功能受损、过多依赖安眠药。睡眠进程和连续性方面：总睡眠时间（TST）、睡眠效率（SE）、睡眠维持率（SMT）均短于对照组,清醒时间（WASO）、睡眠潜伏期（SL）长于对照组;睡眠结构方面：N1、N2比例长于对照组,N3、REM比例短于对照组;REM指标：REM潜伏期（RL）、REM周期数、REM时间（RT）均短于对照组,REM密度（RD）、REM活动度（RA）、REM强度（RI）均长于对照组。在抑郁症失眠组中,HAMD总分与,TST、TIB、SE、SMT、RL显著负相关;与RD、RA、RI正相关;HAMA总分与TST、TIB、SE、SMT负相关;PSQI总分与TST、TIB、SE、SMT显著负相关;睡眠潜伏期因子与SL、N2％显著负相关;睡眠持续性因子与TST、TIB负相关;催眠药物因子与SE、SMT、SL、N2％正相关。结论抑郁症相关性失眠患者失眠症状与普通失眠症相似;多导睡眠图的结果表明存在睡眠进程、睡眠结构及REM指标系列改变;抑郁的严重程度与REM指标相关,REM睡眠的改变可能是特异性的,可作为抑郁症诊断的参考。     

Open-trial response to antidepressant treatment in elderly patients with mixed depression and cognitive impairment

We report open-trial antidepressant response in 16 inpatients with mixed symptoms of depression and cognitive impairment, compared to 16 elderly depressives without cognitive impairment. Criteria for adequate treatment specified a steady-state plasma nortriptyline level of 50-150 ng/ml for 4 consecutive weeks or a minimum of six treatments with electroconvulsive therapy. Ten of 16 mixed-symptom patients showed a drop in Hamilton depression ratings greater than or equal to 50% during treatment. Similarly, Blessed dementia ratings declined significantly; the % change in Blessed dementia ratings was significantly correlated with improvement in Hamilton depression ratings. By contrast, Folstein mini-mental state scores did not change significantly during treatment. Six of 16 (37.5%) patients showed resolution of cognitive impairment with adequate treatment of depression. Mixed-symptom patients diagnosed as suffering from major depression (with cognitive impairment) showed more robust pre-post treatment differences, particularly in Hamilton, Folstein, and Blessed dementia scores, than did mixed patients diagnosed as having primary degenerative dementia (with depression). In cognitively intact elderly depressives, the mean % change in Hamilton ratings was 72% (4.3), not significantly different from mean % change in mixed-symptom patients (57.4 +/- 29.9). The proportion of intact depressives showing a reduction greater than or equal to 50% in Hamilton depression ratings was significantly greater (93.8%) than in the mixed group (62.5%). In both groups, 81.3% of patients (13 of 16 in each cell) had a final Hamilton rating less than or equal to 10. These data suggest that elderly patients with mixed depression and cognitive impairment respond to treatment similar to that used in cognitively intact elderly depressives. A controlled study of antidepressant treatment in mixed-symptom patients is warranted.     

EEG findings in depressive pseudodementia and dementia with secondary depression

We report EEG findings in 33 elderly patients with mixed symptoms of depression and dementia, followed longitudinally to confirm diagnosis. Two groups of patients, dementia with depressive features (mixed-DEM, group I, n = 23) and patients with depressive pseudodementia (mixed-DEP, group II, n = 10), were defined. In addition, we also included, for comparison purposes, 35 patients with probable AD without depressive features (group III), 23 patients with major depression without cognitive impairment (group IV), and 61 healthy elderly controls (group V). We found significant group differences on waking EEGs between those mixed patients who did well after treatment for depression (depressive pseudodementia) compared to patients having dementia with secondary depression. The differences paralleled those between the 'pure' groups of demented and depressed patients. In patients with either depression or depressive pseudodementia, the EEG was usually normal or showed only mild abnormalities. In contrast, the majority of patients with either dementia or dementia with secondary depression had abnormal EEGs, with approximately one-third having moderate (or severe) abnormalities. Although the EEG was usually normal or only mildly abnormal in patients with pseudodementia or depression, these groups (II and IV) did show a significant slowing of the dominant posterior rhythm compared to controls. They also had a higher percentage of generalized abnormal EEGs than controls and this difference was significant between group IV (depression) and controls.     

Polysomnographic and symptomatological analyses of major depressive disorder patients treated with mirtazapine.

OBJECTIVE: This study aimed to characterize the effects of mirtazapine on polysomnographic sleep, especially slow wave sleep (SWS) and rapid eye movement (REM) sleep, as well as its effects on clinical symptoms in patients with major depressive disorder (MDD). METHOD: Sixteen MDD patients were treated with mirtazapine 30 mg taken 30 minutes before bedtime. Polysomnographic and subjective sleep, as well as other clinical data, were collected at baseline and on Days or Nights 2, 9, 16, 30, and 58 during treatment. We used repeated measures analysis of variance, including pairwise comparison, to analyze data statistically. RESULTS: Mirtazapine administration increased total SWS and the SWS in the first sleep cycle, but not SWS in the second sleep cycle. The medication increased REM latency and the duration of the first REM episode; it also decreased the number of REM episodes. Simultaneously, mirtazapine significantly reduced wake-after-sleep onset and scores on the Athens Insomnia Scale. After patients took the medication, scores on the Hamilton Depression Rating Scale-17 (HDRS-17) decreased rapidly and continuously. The changes on the Beck Depression Inventory-II were consistent with those on the HDRS-17. The medication has a tendency to increase weight. CONCLUSIONS: Mirtazapine significantly improved sleep quality, reversed sleep markers of depression, and reduced depressive symptoms in this group of MDD patients.     

Cerebral glucose metabolic response to combined total sleep deprivation and antidepressant treatment in geriatric depression.

OBJECTIVE: The treatment of geriatric depression is complicated by a variable and delayed response to antidepressant treatment. The present study was undertaken to test the hypothesis that combined total sleep deprivation and paroxetine treatment would produce a persistent reduction in glucose metabolism in the anterior cingulate cortex similar to that reported after long-term antidepressant treatment. METHOD: Six elderly depressed patients who met the DSM-IV criteria for major depressive disorder and six age-matched comparison subjects underwent serial positron emission tomography (PET) studies at baseline, after total sleep deprivation, after recovery sleep (after the initial paroxetine dose), and after 2 weeks of paroxetine treatment (patients only). The PET data were analyzed by using statistical parametric mapping methods. RESULTS: The patients' scores on a 13-item version of the Hamilton Depression Rating Scale were decreased after total sleep deprivation, after recovery sleep, and after 2 weeks of treatment. The Hamilton depression scores of the comparison subjects were not significantly altered. In the patients, the greatest reductions in normalized, relative glucose metabolism after sleep deprivation were observed in the anterior cingulate cortex (Brodmann area 24), and they persisted after recovery sleep and antidepressant treatment. The comparison subjects demonstrated increased metabolism in these areas. CONCLUSIONS: Improvement in the patients' depressive symptoms was accompanied by reduced glucose metabolism in the right anterior cingulate cortex and right medial frontal cortex. These preliminary data indicate that in elderly depressed patients, total sleep deprivation may accelerate the clinical and glucose metabolic response to antidepressant treatment.     

Sleep deprivation in chronic somatoform pain-effects on mood and pain regulation

Sleep deprivation was found to exert complex effects on affective dimensions and modalities of pain perception both in healthy volunteers and patients with major depression. Considering multifaceted links between mood and pain regulation in patients with chronic somatoform pain, it is intriguing to study sleep deprivation effects for the first time in this group of patients. Twenty patients with a somatoform pain disorder according to ICD-10 diagnostic criteria were sleep-deprived for one night, followed by one recovery night. Clinical pain complaints (visual analog scale), detection- and pain thresholds (temperature and pressure) as well as mood states (Profile of Mood States) were assessed on the day prior to the experiment, on the day after sleep deprivation and on the day after recovery sleep. We found a discrepancy between significantly increased clinical pain complaints and unaltered experimental pain perception after sleep deprivation. Only the clinical pain complaints, but not the experimental pain thresholds were correlated with tiredness-associated symptoms. Total mood disturbances decreased and feelings of depression and anger improved significantly after sleep deprivation. However, these changes were not correlated with a change in clinical pain perception. We conclude that sleep deprivation may generally change the reagibility of the limbic system, but mood processing and pain processing may be affected in an opposite way reflecting neurobiological differences between emotional regulation and interoceptive pain processing.     

Endogenous depression improvement and REM pressure.

In the treatment of endogenous depression by rapid eye movement (REM) sleep deprivation, depression improvement, measured on Hamilton and Global scales, correlated positively and significantly (P less than .05) with REM pressure (increase of REM sleep stimulated by REM sleep deprivation). This dose-response relationship suggests that (1) REM pressure was an indicator of a process that mediated the antidepressant effects of REM sleep deprivation, and (2) since improvement varied with stimulation of REM sleep, an unknown stimulus of REM sleep is a naturally occurring, endogenous antidepressant.     

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。     

Fatigue in obstructive sleep apnea: driven by depressive symptoms instead of apnea severity?

OBJECTIVE: Obstructive sleep apnea is a common and frequently devastating illness that often includes significant fatigue. Fatigue is also a hallmark depressive symptom. The authors wondered if depressive symptoms in patients with obstructive sleep apnea would account for some of the fatigue beyond that explained by obstructive sleep apnea severity. METHOD: Sixty patients with obstructive sleep apnea-i.e., score >/=15 on the respiratory disturbance index (mean score=49; range=15-111)-underwent polysomnography and completed the Center for Epidemiological Studies Depression Scale (CES-D Scale), Profile of Mood States (POMS), and Medical Outcomes Study surveys. Data were analyzed by using hierarchical regression, with POMS fatigue score as the dependent variable (step 1, forced entry of apnea severity variables; step 2, forced entry of CES-D Scale score). RESULTS: Whereas score on the respiratory disturbance index and the percent of time oxygen saturation was <90% together accounted for 4.2% of variance in scores on the POMS fatigue scale, the CES-D Scale score accounted for 10 times the variance (i.e., an additional 42.3%) in POMS fatigue scale score. CONCLUSIONS: After obstructive sleep apnea severity was controlled, higher levels of depressive symptoms were dramatically and independently associated with greater levels of fatigue. Assessment and treatment of mood symptoms-not just treatment of the disordered breathing itself-might reduce the fatigue experienced by patients with obstructive sleep apnea.     

Sleep and manipulations of the sleep-wake rhythm in depression

OBJECTIVE: Disturbed sleep is typical for most depressed patients and complaints about disordered sleep are the hallmarks of the disorder. Polysomnographic sleep research has demonstrated that besides impaired sleep continuity, sleep in depression is characterized by a reduction of slow wave sleep and a disinhibition of random eye movement (REM) sleep, with a shortening of REM latency, a prolongation of the first REM period and increased REM density. METHOD: Our own experimental work has focused on the reciprocal interaction hypothesis of non-REM and REM sleep regulation as a model to explain the characteristic features of depressed sleep. RESULTS: In agreement with the major tenet of this model, administration of cholinomimetics provoked shortened REM latency in healthy subjects and led to an even stronger REM sleep disinhibition in depressed patients. Manipulations of the sleep-wake cycle, such as sleep deprivation or a phase advance of the sleep period, alleviate depressive symptoms. CONCLUSION: These data indicate a strong bidirectional relationship between sleep, sleep alterations and depression.     

Prediction of antidepressant effects of sleep deprivation by metabolic rates in the ventral anterior cingulate and medial prefrontal cortex.

OBJECTIVE: Sleep deprivation has been shown to have an antidepressant benefit in a subgroup of depressed patients. Functional imaging studies by the authors and others have suggested that patients with elevated metabolic rates in the anterior cingulate gyrus at baseline are more likely to respond to either sleep deprivation or antidepressant medications than patients with normal metabolic rates. The authors extend their earlier work in a larger group of patients and explore additional brain areas with statistical probability mapping. METHOD: Thirty-six patients with unipolar depression and 26 normal volunteers were studied with positron emission tomography before and after sleep deprivation. Response to sleep deprivation was defined as a 40% or larger decrease in total scores on the Hamilton Depression Rating Scale. RESULTS: One-third of the depressed patients had a significant response to sleep deprivation. Responders had higher relative metabolic rates in the medial prefrontal cortex, ventral anterior cingulate, and posterior subcallosal gyrus at baseline than depressed patients who did not respond to sleep deprivation and normal volunteers. Lower Hamilton depression scores correlated significantly with lower metabolic rates in the left medial prefrontal cortex. After sleep deprivation, significant decreases in metabolic rates occurred in the medial prefrontal cortex and frontal pole in the patients who responded positively to sleep deprivation. CONCLUSIONS: High pretreatment metabolic rates and decreases in metabolic rates after treatment in the medial prefrontal cortex may characterize a subgroup of depressed patients who improve following sleep deprivation and, perhaps, other antidepressant treatments.     

Depression and dementia

Specific symptoms of depression in aged subjects are presented in the paper. Cognitive dysfunctions in elder depressive patients (so called pseudodementia) as well as comorbidity of dementia with depression are special diagnostic problems. Both etiopathogenetic and clinical issues are discussed.