Major depressive disorder, alcoholism, and reduced natural killer cell cytotoxicity. Role of severity of depressive symptoms and alcohol consumption

Depression and alcohol abuse have been associated with alterations in cell-mediated immune function. This study directly compared the effects of depression, alcoholism, and their joint contribution to reduce natural killer cell cytotoxicity. Natural killer cell activity was significantly lower in both depressed (n = 18) and alcoholic (n = 19) patients compared with control subjects (n = 50). In addition, patients with a dual diagnosis of either alcohol abuse and secondary depression (n = 9) or depression with a history of alcohol abuse (n = 26) demonstrated a further decrease in natural killer cell activity compared with that found in patients with either depression or alcoholism alone. While both depression and alcoholism are separately associated with a reduction of natural killer cell activity, subgroups of patients in whom the diagnoses of alcoholism and depression coexist show a further decrement in natural killer cell function.     

Nocturnal sleep in severely mentally retarded children: abnormal EEG patterns in sleep cycle

Sleep EEG patterns in 43 mentally retarded children (from 4 months to 80 years of age) were studied throughout nocturnal sleep and the following results were obtained. (1) Twenty-two cases evidenced normal sleep patterns that could be classified into 6 stages. (2) The 21 other cases showed some abnormal sleep EEG patterns as follows: (a) absence of sleep spindles (n = 18) which included cases of high voltage fast activity (n = 2) and cases of low voltage activity throughout nocturnal sleep (n = 3); (b) indistinguishable delta and theta activities (n = 1), extreme spindle-like pattern (n = 1), absence of REM sleep (n = 1). (3) The severely mentally retarded children under 18 months had definitely decreased spindle activity in comparison to the values obtained by other authors from normal children. (4) The majority of the abnormal sleep EEG patterns occurred during light sleep. (5) A significant decrease in DQ was found in children with abnormal sleep patterns throughout NREM sleep as compared with those in whom abnormal EEGs occurred only during stages 1 and 2. (6) It was concluded that the EEG recorded in nocturnal sleep may serve as a useful indicator of abnormality in mentally retarded children.     

CAP variables and arousals as sleep electroencephalogram markers for primary insomnia.

OBJECTIVE: Polysomnographic (PSG) measures consistently reflect poor sleep quality and effective treatment in insomniac patients. METHODS: The PSG findings of 47 patients (18 M and 29 F, 42.5+/-10 years) meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for a diagnosis of primary insomnia were compared with those of 25 age- and gender-balanced healthy subjects (controls) without sleep complaints. After one adaptation night to the sleep lab, each patient underwent two randomized double-blind PSG recordings. Twenty-four patients followed a placebo-drug sequence and 23 a drug-placebo succession. Active treatment consisted of widely used hypnotic drugs, i.e. zolpidem, triazolam, zopiclone, brotizolam. Conventional PSG measures, electroencephalogram (EEG) arousals and CAP variables (including phase A subtypes) were quantified and statistically analyzed. RESULTS: Compared to controls, insomniac patients under placebo showed a significant increase of CAP rate, subtypes A1 and A2, EEG arousals, nocturnal wakefulness and stage 1, associated with reduced values of total sleep time and slow wave sleep (stages 3 and 4). In insomniac patients, sleep quality was significantly improved by hypnotic treatment. Compared to placebo, active medication significantly reduced CAP rate, subtypes A1 and A2, but had only marginal effects on subtypes A3 and on EEG arousals. Under hypnotic treatment total sleep time, nocturnal awakenings, stage 1 and slow wave sleep recuperated normal values. The most significant correlation between sleep quality and PSG variables was found for CAP rate (P<0.0001). CONCLUSIONS: PSG investigation extended to CAP variables and EEG arousals can be an important procedure for the diagnosis of primary insomnia and evaluation of treatment efficacy.     

Patients with systemic lupus erythematosus differ from healthy controls in their immunological response to acute psychological stress

Clinical observations suggest that psychological stress induces exacerbation of disease activity in patients with systemic lupus erythematosus (SLE). In order to determine whether SLE patients differ from healthy controls in their stress response, we analyzed heart rate, blood pressure, catecholamine concentration, lymphocyte subpopulations, natural killer (NK) cell activity, and expression of beta-adrenoceptors on PBMC before, immediately after, and 1 h after a public speaking task in 15 SLE patients and 15 healthy subjects. Both groups demonstrated similar psychological, cardiovascular, and neuroendocrine responses to acute stress. However, natural killer (CD16(+)/CD56(+)) cell numbers transiently increased after stress exposure, with significantly less pronounced changes in SLE patients. In addition, NK activity increased in healthy controls (n = 8) but not in SLE patients (n = 4) after acute stress. Furthermore, the number of beta(2)-adrenoceptors on PBMC significantly increased only in healthy subjects (n = 8) after stress but not in SLE patients (n = 7). These data indicate that SLE patients differ from healthy controls in stress-induced immune responses.     

Nocturnal sleep in infants with congenital cerebral malformation

Sleep EEG patterns in 17 infants with cerebral malformations (4 months to 4 years of age) were studied throughout nocturnal sleep and the following results were obtained. Seven cases evidenced normal sleep/wakefulness EEG patterns that could be classified into 6 stages. Ten cases showed abnormal sleep EEG patterns as follows: absence of sleep spindles (n = 7) which included cases of absence of EEG patterns characteristic of wakefulness, NREM sleep and REM sleep (n = 5), no characteristic EEG patterns of stages 1-4 (n = 1) and stages W, 1, 2 and REM (n = 1) and the remaining cases with absence of spindles (n = 1), and spindles with an extremely low incidence (n = 2). Short sleep and long awaking times, and no delta rhythmicity during the night, were noted in 5 out of 17 subjects. A significant decrease of DQ was found in subjects with indistinguishable stages including stages W, 1, 2 and REM, as compared with those patients whose stages were all distinguishable.     

Abnormal nocturnal melatonin secretion and disordered sleep in abstinent alcoholics.

BACKGROUND: Alcoholic patients show prominent disturbance of sleep as measured by electroencephalogram, with difficulties in the onset and maintenance of sleep. Given the role of melatonin in the regulation of the sleep-wake cycle, this study examined the relationship between nocturnal expression of melatonin and sleep in alcoholics as compared with control subjects. METHODS: Alcoholic patients (n = 11) and comparison control subjects (n = 10) underwent all-night polysomnography and serial blood sampling every 30 min from 10:00 PM to 6:30 AM for measurement of circulating levels of melatonin and cortisol. RESULTS: Coupled with prolonged sleep latency, alcoholics showed lower levels of melatonin during the early part of the night and a delay in the onset of the nocturnal plateau or peak value of melatonin as compared with control subjects. The nocturnal delay of melatonin correlated with prolonged sleep latency. Circulating levels of cortisol were lower during the early part of the night and higher in the late part of night in the alcoholics as compared with the control subjects. CONCLUSIONS: A delay in the nocturnal rise of melatonin may contribute to disordered sleep in chronic alcoholics, with implications for the use of melatonin in the treatment of insomnia in recovering alcoholics.     

Increased nocturnal interleukin-6 excretion in patients with primary insomnia: a pilot study

The aim of the present study was to investigate whether there is a difference in evening/nocturnal interleukin-6 (IL-6) serum excretion in patients with primary insomnia compared to controls. We hypothesized that in insomniac patients, the excretion of evening/nocturnal IL-6 is enhanced, like observed in aged adults and after sleep deprivation in healthy subjects. We studied IL-6 serum concentrations in 11 patients (two males and nine females) with primary insomnia and 11 age and gender-matched healthy controls. Sleep was monitored polysomnographically for three consecutive nights. The measurement of IL-6 (from 19:00 h to 09:00 h) in 2-h intervals were performed prior to and during the last laboratory night. Polysomnographically determined sleep parameters and subjective ratings of sleep demonstrated clear-cut impairments of sleep in the insomniac group. Nocturnal IL-6 secretion was significantly increased (p<.05) in insomniac patients for the whole measurement period (mean area under the curve+/-SD: 27.94+/-14.15 pg/ml x 2h) compared to controls (16.70+/-7.64 pg/ml x 2h). Total IL-6 secretion correlated inversely with subjectively perceived sleep quality and amount of slow wave sleep in the insomniac patients. Amount of Wake Time correlated positively with IL-6 excretion in insomniacs. The results of the present study demonstrate significantly increased nocturnal IL-6 secretion in insomniacs. It might be speculated that chronic primary insomnia with polysomnographically documented sleep impairments activates the production of IL-6 analogous to sleep deprivation studies in healthy subjects. This might also implicate a higher risk for inflammatory and cardiovascular diseases in patients with chronic insomnia.     

Coemergence of insomnia and a shift in the Th1/Th2 balance toward Th2 dominance

OBJECTIVES: Insomnia is associated with physical and mental disorders. We examined the effect of insomnia on immune functions, focusing on the T helper 1 (Th1)/ T helper 2 (Th2) balance, by a cross-sectional design. METHODS: We provided a self-administered questionnaire to evaluate sleep habits, smoking and medical disorders to 578 men without any toxic exposure (20-64 years old), and measured natural killer (NK) cell activity in 324 men and production of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) after stimulation with phytohemagglutinin in 254 men. According to the criteria of DSM-IV, in which insomnia is classified into primary and secondary insomnia, we assessed the effect of insomnia on immune functions, controlling for age and smoking in groups with and without medical disorders. RESULTS: The prevalence of insomnia in the present study was 9.2%. In the absence of medical disorders, insomniac men had a significantly lower IFN-gamma and ratio of IFN-gamma to IL-4 than noninsomniac men. Men with insufficient sleep or difficulty initiating sleep (DIS) had a significantly lower IFN-gamma to IL-4 ratio than those not suffering from insufficient sleep or DIS. In the presence of medical disorders, insomniac men had significantly higher IL-4 than noninsomniac men. Men with difficulty maintaining sleep (DMS) had a significantly lower IFN-gamma to IL-4 ratio than men without DMS. NK cell activity was independent of insomnia. CONCLUSIONS: The present results showed a link between insomnia unrelated to medical disorders and a shift in the Th1/Th2 balance toward Th2 dominance, indicating that the relationship between sleep quality and the etiology of immune-related diseases should be reconsidered.     

Motor activity and perception of sleep in depressed patients.

Subjectively experienced sleep patterns often differ from observed sleeping behavior in insomniacs. Sleep patterns have been evaluated by measurements of motor activity in healthy subjects and insomniacs, but results may depend on the insomnia subtype. Sleep disturbances are frequent complaints in depression, but the influence of psychopathology on activity measurements remains elusive. Therefore, the relationship between reported sleep complaints and motor activity was studied in patients with major depression. Severity of depression was documented in depressed inpatients by observer-(HAMD) and self-rated scales (DACL, SHAPS-D). Self-reports of sleep were obtained by Pittsburgh Sleep Quality Index (PSQI) and daily sleep logs (DSL). Motor activity was continuously recorded over 72 h by actigraphy. 'Good' sleepers showed less motor activity during the night compared to 'poor' sleepers (p<0.01). Patients with high HAMD scores (> or = 18) showed greater nocturnal motor activity and less sleep quality compared to patients with low HAMD scores (p<0.01). When controlling for age and severity of depression, partial correlation was found to be significant between perceived daily sleep quality and nocturnal motor activity (r = -0.63, p<0.01). There was a significant effect of nocturnal motor activity as a covariate on disturbances of subjective sleep quality and severity of depression as the main effect (p<0.01). In depressed patients, nocturnal motor activity seems to be an indicator of experienced sleep disturbances. The results warrant further controlled studies to evaluate the role of psychological factors for objective measurements and subjective perception of sleep patterns.     

Nocturnal cortisol and melatonin secretion in primary insomnia

The present study investigated evening and nocturnal serum cortisol and melatonin concentrations in patients with primary insomnia to test if this clinical condition is accompanied by an increase of cortisol secretion and a simultaneous decrease of nocturnal melatonin production. Ten drug-free patients (4 males, 6 females) with primary insomnia (mean age+/-S.D.: 39.2+/-9.1 years) and 10 age- and gender-matched healthy controls participated in the study. All subjects spent three consecutive nights in the sleep laboratory with polysomnography. Measurement of cortisol and melatonin (from 19:00 h to 09:00 h) was performed prior to and during the last laboratory night. Contrary to expectation, cortisol secretion did not differ between healthy controls and insomniac patients. On the other hand, nocturnal melatonin production was significantly diminished in insomniac patients. Polysomnographically determined sleep patterns, in contrast to subjective ratings of sleep, demonstrated only minor alterations of sleep in the insomniac group. The lack of increased cortisol secretion in the patients with primary insomnia indicates that results from studies on the biological consequences of experimental sleep loss in healthy subjects cannot be applied to primary insomnia in general, especially if there are only minor objective sleep alterations. In spite of the negligible objective sleep disturbances in the present sample, nocturnal melatonin production was reduced, which tentatively suggests a role for this hormone in primary insomniacs. The pathophysiological significance of this finding is, however, still a matter of debate.     

Dissociation of inflammatory markers and natural killer cell activity in major depressive disorder

Major depressive disorder is associated with increases in infectious disease risk as well as the incidence of inflammatory disorders. Declines of natural killer (NK) cell activity are reliably found in depression, whereas other studies report evidence of inflammation in depressed patients. The potential association between NK activity and circulating markers of immune activation has not been previously examined in the context of major depression. In this study, we measured levels of NK activity, circulating levels of interleukin-6 (IL-6), soluble interleukin-2 receptor, and acute phase proteins in 25 male patients with current major depressive disorder and 25 age, gender, and body weight comparable controls. As compared to controls, patients with major depressive disorder showed lower NK activity (p = .05) and higher circulating levels of IL-6 (p < .05). Levels of NK activity were not correlated with IL-6 or with other markers of immune activation. The independent effect of depression on inflammatory markers and natural killer immune responses has implications for understanding individual differences in the adverse health effects of major depressive disorder.     

The tryptophan depletion test: impact on sleep in primary insomnia - a pilot study

The application of the tryptophan depletion test is based on the assumption that the decrease of plasma or serum tryptophan concentration following the ingestion of a tryptophan-free amino acid drink reflects a central nervous effect on serotonin metabolism. In the present study the impact of tryptophan depletion on polysomnographically recorded sleep in patients with primary insomnia was studied. Fifteen patients with primary insomnia slept for four nights in the sleep laboratory. Prior to the fourth night the tryptophan depletion test was applied. Sleep EEG variables served as outcome parameters. Patients with primary insomnia, compared to baseline values showed a highly significant decrease of serum tryptophan concentrations after the amino acid drink. Concerning sleep parameters, stage 1 (% sleep period time=SPT) was increased, whereas stage 2 (% SPT) was decreased. Indices of phasic activity of rapid eye movement (REM) sleep (REM density) were increased after the tryptophan depletion compared to baseline. The results suggest a negative impact of tryptophan depletion on sleep continuity and a stimulating effect on phasic measures of REM sleep in patients with primary insomnia.     

脑电生物反馈辅助治疗老年失眠症的疗效观察

目的 研究脑电生物反馈疗法辅助治疗老年失眠症的效果.方法 将67例老年失眠症患者随机分为研究组（34例,使用右佐匹克隆合并脑电生物反馈治疗8周）和对照组（33例,单用右佐匹克隆治疗8周）.采用多导睡眠（PSG）监测技术和匹兹堡睡眠质量指数量表（PSQI）评定疗效.结果 治疗后第8周末,两组多导睡眠脑电图中实际睡眠总时间、睡眠效率、睡眠维持率、睡眠潜伏期、REM（快速眼动）潜伏期、REM睡眠比例、夜间觉醒次数、觉醒总时间较治疗前显著改善（P＜0.05）;且研究组睡眠脑电图各项数据与对照组比较差异有统计学意义（P＜0.05）.两组PSQI评分均低于各自治疗前（P＜0.05）,研究组PSQI评分显著低于对照组（P＜0.05）.结论 脑电生物反馈疗法辅助治疗老年失眠症有较好的效果.     

Correlation between depressive symptoms and nocturnal disturbances in Japanese patients with Parkinson's disease

Depression and nocturnal disturbances are frequent in patients with Parkinson's disease (PD). The aim of this study was to determine the correlation between depressive symptoms and nocturnal disturbances in patients with PD in Japan. The subjects of this multi-center cross-sectional study were 188 patients with PD and 144 age-matched controls who were assessed for nocturnal disturbances by the Parkinson's disease sleep scale (PDSS) and for depressive symptoms by Zung Self-Rating Depression Scale (SDS). Depressive symptoms (SDS score of > or =40) were identified in 122 patients (64.9%). The SDS was significantly higher in PD patients than control subjects. The stepwise regression model identified PDSS (p<0.001) and Unified Parkinson's Disease Rating Scale I (mental state) (p=0.002) as significant determinants of SDS. Stepwise regression analysis identified item 15 (daytime sleepiness) (p=0.002), item 13 (early morning tremor) (p=0.008), item 12 (nocturnal dystonia) (p=0.015), and item 3 (sleep maintenance insomnia) (p=0.026) as significant predictors of SDS. Our results indicated that depressive symptoms in PD correlate significantly with nocturnal disturbances, and that daytime sleepiness, dystonia, tremor and sleep fragmentation are the most common nocturnal disturbances in depressed patients with PD.     

Nocturnal epileptiform EEG discharges, nocturnal epileptic seizures, and language impairments in children: review of the literature

This review addresses the effect on language function of nocturnal epileptiform EEG discharges and nocturnal epileptic seizures in children. In clinical practice, language impairment is frequently reported in association with nocturnal epileptiform activity. Vice versa, nocturnal epileptiform EEG abnormalities are a common finding in children with specific language impairment. We suggest a spectrum that is characterized by nocturnal epileptiform activity and language impairment ranging from specific language impairment to rolandic epilepsy, nocturnal frontal lobe epilepsy, electrical status epilepticus of sleep, and Landau-Kleffner syndrome. In this spectrum, children with specific language impairment have the best outcome, and children with electrical status epilepticus of sleep or Landau-Kleffner syndrome, the worst. The exact nature of this relationship and the factors causing this spectrum are unknown. We suggest that nocturnal epileptiform EEG discharges and nocturnal epileptic seizures during development will cause or contribute to diseased neuronal networks involving language. The diseased neuronal networks are less efficient compared with normal neuronal networks. This disorganization may cause language impairments.     

Are there gender differences in objective and subjective sleep measures? A study of insomniacs and healthy controls

It is well known that insomnia is more frequent in women than in men throughout all age groups. In this respect insomnia resembles other psychiatric disorders that occur more frequently in women such as anxiety and depressive disorders. Since insomnia is frequently a symptom of anxiety and depression, it remains an open question whether the comorbidity with psychiatric disorders fully explains the gender differences in the prevalence of insomnia or whether gender influences sleep independently from psychiatric conditions. We analyzed sleep measures of patients diagnosed with a primary insomnia (n=86) and of an age- and sex-matched healthy control group (n=86) by polysomnography; additionally, subjective rating scales were available for 70 patients and 54 controls matched for mean age and sex ratio. Surprisingly, none of the sleep continuity measures (sleep duration, sleep efficiency, arousal index, and wake%), nor slow wave or REM sleep % showed significant gender differences in both insomniacs and healthy controls. Also, subjective estimates of sleep quality were comparable in both sexes. As expected, insomniacs strongly differed from the control group in all subjective measures of sleep. Polysomnography showed significantly reduced sleep duration and efficiency, increased arousal index, and slightly, but significantly, less REM sleep in the insomniacs as compared to the healthy controls. These studies indicate that gender seems to have, if any, relatively little influence on sleep per se. We hypothesize that the clear gender differences in the prevalence of insomnia are caused predominantly by gender differences in the prevalence of anxiety and depression. Primary insomnia may be, at least in a part of the cases, a subclinical or subthreshold form of anxiety or depression.     

Cellular adhesion molecule expression, nocturnal sleep, and partial night sleep deprivation

Sleep is hypothesized to have a role in the regulation of the immune system. This study evaluated the nocturnal expression of cellular adhesion molecules, Mac-1 and L-selectin on monocytes and lymphocytes during a full nights sleep and following a partial night of sleep deprivation (PSD). Healthy male subjects (n=16) had an increase in the percentage of Mac-1 positive lymphocytes across the baseline night. Whereas, the percentage of Mac-1 positive lymphocytes was reduced and L-selectin positive lymphocytes and monocytes were greater during the PSD night as compared to the baseline night. These data indicate that acute sleep disruption is associated with alterations in cellular adhesion molecule expression, with implications for the regulation of immune cell trafficking.     

Biological measures and cellular immunological function in depressed psychiatric inpatients

Thirty depressed psychiatric inpatients, including 18 with a diagnosis of major depression, and 25 hospital staff controls were compared with respect to cellular immune function--that is, mitogen responsiveness to concanavalin A (con A), phytohemagglutinin (PHA), and pokeweed mitogen (PWM); natural killer cell (NK) activity; and T cell subsets, including helper/inducer T cells (CD4) and suppressor/cytotoxic cells (CD8). Only physically healthy subjects, who had not used psychoactive medications (except for low dose benzodiazepines) or other medications known to affect the immune system for at least 14 days, were included. Paired comparisons of the immune measures of patients with a DSM-III diagnosis of major depression (n = 18) with their controls demonstrated a statistically significant reduction of the patients' con A response. In addition, the patients with major depression had significantly lower con A and PHA responses than the combined patients with other forms of depression (atypical, dysthymic, or atypical bipolar). There was no indication that severity of depression, dexamethasone suppression test status, benzodiazepine use, or age accounted for the differences in immune function. A possibly important, unexpected finding was that antihistamine use was associated with lower immune function.     

Nocturnal epileptiform EEG discharges,nocturnal epileptic seizures,and language impairments in children: Review of the literature

This review addresses the effect on language function of nocturnal epileptiform EEG discharges and nocturnal epileptic seizures in children. In clinical practice, language impairment is frequently reported in association with nocturnal epileptiform activity. Vice versa, nocturnal epileptiform EEG abnormalities are a common finding in children with specific language impairment. We suggest a spectrum that is characterized by nocturnal epileptiform activity and language impairment ranging from specific language impairment to rolandic epilepsy, nocturnal frontal lobe epilepsy, electrical status epilepticus of sleep, and Landau–Kleffner syndrome. In this spectrum, children with specific language impairment have the best outcome, and children with electrical status epilepticus of sleep or Landau–Kleffner syndrome, the worst. The exact nature of this relationship and the factors causing this spectrum are unknown. We suggest that nocturnal epileptiform EEG discharges and nocturnal epileptic seizures during development will cause or contribute to diseased neuronal networks involving language. The diseased neuronal networks are less efficient compared with normal neuronal networks. This disorganization may cause language impairments.     

A structured psychiatric intervention for cancer patients. II. Changes over time in immunological measures

We evaluated the immediate and long-term effects on immune function measures of a 6-week structure psychiatric group intervention for patients with malignant melanoma. Along with a reduction in levels of psychological distress and greater use of active coping methods, the following immune changes were seen at the 6-month assessment point in the intervention-group patients (n = 35) compared with controls (n = 26): significant increases in the percent of large granular lymphocytes (defined as CD57 with Leu-7) and natural killer (NK) cells (defined as CD16 with Leu-11 and CD56 with NKH1) along with indications of increase in NK cytotoxic activity; and a small decrease in the percent of CD4 (helper/inducer) T cells. At the 6-week follow-up point, the majority of these changes were not yet observable. The results indicate that a short-term psychiatric group intervention in patients with malignant melanoma with a good prognosis was associated with longer-term changes in affective state, coping, and the NK lymphoid cell system. Affective rather than coping measures showed some significant correlations with immune cell changes.