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Accelerometers are widely accepted as practical wearable devices capable of measuring and assessing physical activity. These devices may, however, be subject to errors which could impact on their ability to acquire an accurate step count. A limited number of studies have examined the effects of body mass index (BMI) on the accuracy of accelerometers functioning as step counters. It has been suggested that BMI may not be the best indicator of adiposity. The aim of the present study was to assess the effects of BMI and abdominal volume on the accuracy of a step count obtained from a tri-axial accelerometer. Accelerometers were placed directly onto the skin at the chest, waist and lower back of 12 participants. Participants then walked on a motorized treadmill at 0.89 m/s and 1.34 m/s. Analysis of the results indicated that BMI and abdominal volume did not affect the accuracy of the step count obtained from accelerometers under any conditions. Walking speed, however, had a significant effect with step count accuracy decreasing at the slower speed.

Few studies have examined relationships between perinatal depression and sleep in offspring beyond very early childhood. Eighty-five women classified as high risk for major depressive disorder during pregnancy completed measures of mood and their child's sleep 4-7 years postpartum. Mothers with Beck Depression Inventory-II (BDI-II) scores ≥20 reported more sleep problems in their child, and child sleep disruption was a reasonable predictor of maternal BDI-II. More research is needed to determine causal relationships between perinatal depression and sleep in offspring.

Objective: Sleep disturbances are common in major depressive disorder (MDD), although polysomnographic (PSG) abnormalities are more prevalent in adults than in children and adolescents with MDD. Sleep spindle activity (SPA) is associated with neuroplasticity mechanisms during brain maturation and is more abundant in childhood and adolescence than in adulthood, and as such, may be a more sensitive measure of sleep alteration than PSG in early-onset depression. This study investigated SPA changes related to early-onset MDD, comparing individuals already ill with MDD and individuals at high-risk for MDD with healthy nondepressed controls., Method: The study included 63 participants (8 to 15 years of age): 21 currently depressed individuals, 21 individuals at high risk for MDD based on positive family history of MDD, and 21 healthy control individuals with no personal or family history of psychiatric illness. All participants maintained a regular sleep/wake schedule for 5 days, followed by 2 nights in the laboratory. SPA was analyzed in Stage 2 of non-rapid eye movement sleep., Results: SPA differed significantly between groups, particularly in the late part of the night (F(2,62) = 7.3, p = .001). Although the difference was greatest between the MDD and healthy control groups, both the MDD (p = .0004) and at high-risk groups (p = .02) had significantly lower SPA compared with healthy controls. SPA deficit was more prominent in females than in males (F(5,62) = 5.19, p = .005)., Conclusions: Low SPA characterizes youths with MDD and those at high risk for MDD, particularly girls, suggesting that early-onset depression and risk for the MDD are associated with decreased neuroplasticity., (2010 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

The luminescence of InGaN single quantum wells grown by molecular-beam epitaxy under fixed conditions over a series of c-axis GaN nanowire arrays with different geometrical parameters was studied. For arrays with variable GaN average wire diameters and fixed wire densities, the InGaN luminescence peak shifted to higher energy with decreasing wire diameter. It is shown that this trend cannot be attributed to lateral quantum confinement or diameter-dependent InGaN strain. For arrays with variable wire densities and fixed average diameters, the InGaN emission appeared as two distinct bands of different colours, the relative intensities of which depended on the wire density. By optimizing both the GaN wire density and InGaN growth conditions, the colours of the two different bands were combined to realize phosphor-free white light-emitting diodes. The mechanisms for the dependence of the InGaN luminescence on the geometrical parameters of the GaN nanowire array are discussed.

Objective: Higher body mass index (BMI) has been associated with more sleep disturbance and depressive symptoms, but the combined effects of depression and BMI on sleep have not been studied in children. This study evaluated the relationship between BMI and polysomnography in children with major depressive disorder (MDD), compared to healthy controls (HCs)., Method: The sample of 104 subjects included 72 children, 8-17 years old, with MDD and 32 similarly aged HCs with no personal or family history of psychopathology. BMI was adjusted using the CDC formula for percentiles by age. Subjects were categorized as (1) normal weight (5-84th percentile) or (2) high weight, which included at risk of overweight and overweight (> or = 85th percentile). All analyses were adjusted for sex and Tanner maturational stage scores., Results: In the MDD group only, higher BMI was significantly correlated with decreased sleep efficiency, decreased percentage of rapid eye movement sleep (REM%), and higher percentage of time spent awake and moving (TSPAM). In the HC group only, higher BMI correlated with higher total sleep time. Multivariate analyses revealed significant interactions between the BMI and diagnostic groups for several REM sleep parameters, such that high-weight children from the HC and MDD groups had increases and decreases in REM sleep, respectively. TSPAM increased in the high-weight MDD group, but decreased in the high-weight HC group., Conclusions: Although limited by small sample size, these findings suggest that children and adolescents with MDD and a high BMI have more fragmented sleep than other children. The increased REM sleep patterns observed with MDD in this and other studies normalized in high-weight children with MDD. Prevention and treatment strategies should target both sleep and weight as factors that can potentially influence the development and course of MDD., (Copyright 2010 Elsevier B.V. All rights reserved.)

Objectives: This study evaluated whether sleep over the first 6 months of life was more disturbed in infants born to mothers who were depressed compared with infants from nondepressed mothers., Design: Actigraphy was recorded for 7 consecutive days starting at 2 weeks postpartum and monthly thereafter until 6 months of age. Mothers completed daily sleep/wake diaries. Sleep data at 2 weeks and 6 months postpartum are presented here., Setting: The home environment., Participants: Eighteen healthy, full-term infants, 9 males and 9 females. Seven infants were born to women with no personal or family history of depression; 11 infants were born to women diagnosed with depression or with elevated levels of depression symptoms., Interventions: N/A., Measurements and Results: Total sleep time, sleep latency, sleep efficiency, and number and duration of sleep episodes were computed for nocturnal and daytime sleep in each 24-hour block. Data were coded for risk group (1 = low risk, 2 = high risk), and repeated-measures multivariate analysis of variance contrasted changes in sleep measures at Week 2 and Week 24, between risk groups. The high-risk infants took longer to fall asleep, had lower sleep efficiencies, and had more sleep bouts in the nocturnal sleep period than did low-risk infants. These effects persisted at 6 months postpartum., Conclusions: Maternal depression is associated with significant sleep disturbance in infancy at 2 weeks postpartum that continues through 24 weeks. It remains to be determined if sleep disturbance in infancy confers a greater risk of developing early-onset depression in childhood.

The regulation of the alternation between rapid eye movement sleep (REMS) and non-rapid eye movement sleep (NREMS) is still a matter of much debate. It is also an important topic for psychiatric research, since both sleep components show anomalies in Major Depressive Disorders (MDD) and related syndromes. In previous studies on healthy controls, we showed preferential links of the number of ultradian cycles with REMS-related variables rather than with NREMS-related variables. REMS Latency (RL), for example, was shown to be inversely related to the number of cycles. The present study replicates these analyses in a group of 29 patients with MDD (age range: 23-56; 16 females), after two adaptation nights. Results showed significant correlations between the number of cycles and REMS, and between the number of cycles and RL, whereas correlations with NREMS were not significant. This indirectly supports regulation hypotheses considering REMS as the main focus of the oscillation, inhibiting and interrupting NREMS. Also, when the RL is shorter, there are more ultradian cycles than when the RL is long. This adds an interesting element in the elucidation of the physiological meaning of anomalies of RL.

Objective: The purpose of the study was to evaluate quantitative sleep electroencephalogram (EEG) frequencies in monozygotic twins discordant for chronic fatigue syndrome., Methods: Thirteen pairs of female twins underwent polysomnography. During the first night, they adapted to the sleep laboratory, and during the second night, their baseline sleep was assessed. Visual stage scoring was conducted on sleep electroencephalographic records according to standard criteria, and power spectral analysis was used to quantify delta through beta frequency bands, processed in 6-s blocks. Data were averaged across sleep stage within each twin and coded for sleep stage and the presence or absence of chronic fatigue syndrome (CFS). A completely within-subjects repeated measure multivariate analysis of variance evaluated twin pairs by frequency band by sleep stage interactions and simple effects. The relationship between alpha and delta EEG was also assessed across twin pairs., Results: No significant differences in spectral power in any frequency band were found between those with CFS and their nonfatigued cotwins. Phasic alpha activity, coupled with delta was noted in five subjects with CFS but was also present in 4/5 healthy twins, indicating this finding likely reflects genetic influences on the sleep electroencephalogram rather than disease-specific sleep pathology., Conclusions: The genetic influences on sleep polysomnography and microarchitecture appear to be stronger than the disease influence of chronic fatigue syndrome, despite greater subjective sleep complaint among the CFS twins. EEG techniques that focus on short duration events or paradigms that probe sleep regulation may provide a better description of sleep abnormalities in CFS.

IL-33 is an IL-1 family member recently identified as the ligand for T1/ST2 (ST2), a member of the IL-1 receptor family. ST2 is stably expressed on mast cells and T(h)2 effector T cells and its function has been studied in the context of T(h)2-associated inflammation. Indeed, IL-33 induces T(h)2 cytokines from mast cells and polarized mouse T cells and leads to pulmonary and mucosal T(h)2 inflammation when administered in vivo. To better understand how this pathway modulates inflammatory responses, we examined the activity of IL-33 on a variety of human immune cells. Human blood-derived basophils expressed high levels of ST2 receptor and responded to IL-33 by producing several pro-inflammatory cytokines including IL-1 beta, IL-4, IL-5, IL-6, IL-8, IL-13 and granulocyte macrophage colony-stimulating factor. Next, utilizing a human T(h)2-polarized T cell culture system derived from allergic donor blood cells, we found that IL-33 was able to enhance antigen-dependent and -independent T cell responses, including IL-5, IL-13 and IFN-gamma production. IL-33 activity was also tested on V alpha 24-positive human invariant NKT (iNKT) cells. In the presence of alpha-galactosylceramide antigen presentation, IL-33 dose dependently enhanced iNKT production of several cytokines, including both IL-4 and IFN-gamma. IL-33 also directly induced IFN-gamma production from both iNKT and human NK cells via cooperation with IL-12. Taken together, these results indicate that in addition to its activity on human mast cells, IL-33 is capable of activating human basophils, polarized T cells, iNKT and NK cells. Moreover, the nature of the responses elicited by IL-33 suggests that this axis may amplify both T(h)1- and T(h)2-oriented immune responses.

Objectives: Chronic fatigue syndrome (CFS) has been associated with altered amounts of slow wave sleep, which could reflect reduced delta electroencephalograph (EEG) activity and impaired sleep regulation. To evaluate this hypothesis, we examined the response to a sleep regulatory challenge in CFS., Design: The first of 3 consecutive nights of study served as laboratory adaptation. Baseline sleep was assessed on the second night. On the third night, bedtime was delayed by 4 hours, followed by recovery sleep. Total available sleep time was held constant on all nights., Setting: A research sleep laboratory., Participants: 13 pairs of monozygotic twins discordant for CFS., Interventions: N/A., Measurements and Results: Power spectral analysis quantified slow wave activity (SWA) in the 0.5-3.9 Hz band in successive NREM periods (stage 2, 3, or 4) on each night. To ensure comparability, analyses were restricted to the first 4 NREM periods on each night. Data were coded for NREM period and twin pair. Repeated-measures analysis of variance (ANOVA) contrasted sleep delay effects across NREM periods between twin pairs. A second ANOVA calculated the SWA in each NREM period in recovery sleep relative to baseline SWA. The 2 groups of twins were similar on baseline SWA power. After sleep delay, CFS twins exhibited significantly less SWA power in the first NREM period of recovery sleep and accumulated a smaller percentage of SWA in the first NREM period than their co-twins., Conclusions: CFS is associated with a blunted SWA response to sleep challenge, suggesting that the basic sleep drive and homeostatic response are impaired.

Objective: We evaluated the efficacy of cognitive-behavioral treatment for insomnia in recovering alcoholic patients in an open pilot study., Methods: Seven abstinent alcoholic patients (3 women, mean age 38.6+/-10.8 years) recruited from outpatient and residential treatment facilities met the Diagnostic and Statistic Manual of Mental Disorders - Fourth edition (DSM-IV) criteria for insomnia comorbid with alcohol dependence and participated in eight individual treatment sessions. Participants were free of other medical, psychiatric, and sleep disorders. Daily sleep diaries were completed beginning two weeks before treatment until two weeks after treatment. Measures of sleep, daytime functioning, and drinking were collected., Results: Diary-rated sleep latency [F(2,10)=14.4, p<.001], wake after sleep onset [F(2,10)=7.7, p=.009], and sleep efficiency [F(2,10)=28.3, p<.001] improved as did patient-rated and clinician-rated Insomnia Severity Index (ISI) and the Dysfunctional Beliefs and Attitudes about Sleep - Short Form (DBAS-SF). Compared to pre-treatment, significant post-treatment improvements were found on scales measuring depression and anxiety symptoms, fatigue, and quality of life. No one relapsed to alcohol during treatment., Conclusions: Cognitive-behavioral insomnia therapy may benefit recovering alcoholics with mild to moderate insomnia by improving sleep and daytime functioning. Effects on relapse remain to be determined. Findings need to be interpreted cautiously due to the uncontrolled design and lack of follow-up assessments.

Objective: Self-reported sleep disturbances are present in over 80% of patients with depression. However, sleep electroencephalography (EEG) findings, based on overnight polysomnography have not always differentiated depressed patients from healthy individuals., Method: The present paper will review the findings on sleep EEG studies in depression highlighting how recent technological and methodological advances have impacted on study outcomes., Results: The majority of studies, including our own work, do indicate that sleep homeostasis and sleep EEG rhythms are abnormal in depression, but the sleep disturbances were strongly moderated by gender and age. Melancholic features of depression correlated significantly with low slow-wave activity in depressed men, but not in depressed women. Women with depression showed low temporal coherence of sleep EEG rhythms but the presence or absence of melancholic features did not influence correlations., Conclusion: Diagnostic classification schemas and clinical features of depression may influence sleep EEG findings, but gender may be a more important consideration.

Background: Subjective and objective measures of poor sleep in alcoholic insomniacs predict relapse to drinking. Nonalcoholic insomniacs underestimate their total sleep time (TST) and overestimate their sleep onset latency (SOL) and wake time after sleep onset (WASO) compared with polysomnography (PSG). This study evaluated 3 hypotheses: (1) subjective SOL would predict frequency of future drinking; (2) participants would overestimate SOL and WASO and underestimate TST; and (3) higher amounts of over- and underestimates of sleep at baseline would predict worse drinking outcomes prospectively., Methods: Participants (N=18), mean age 44.6 years (+/-13.2), underwent an adaptation night and then 2 nights of PSG 3 weeks apart. They also provided morning estimates of SOL, WASO, TST, and sleep efficiency (SE). Following the baseline PSG, participants were followed over 12 weeks. A 2-way ANOVA (night x method of measuring sleep) compared results and regression analyses predicted drinking. Drinking outcomes were defined as number of days drinking (DD) and number of heavy-drinking days (HDD) during 2 consecutive 6-week follow-up periods., Results: Most participants (72%) overestimated SOL by a mean of 21.3 (+/-36) minutes compared with PSG [F(1, 14)=7.1, p<0.03]. Unexpectedly, 89% underestimated WASO by a mean difference of 48.7 (+/-49) minutes [F(1, 14)=15.6, p<0.01]. Drinking during the first 6-week study period was predicted by both subjective estimates of WASO and their accuracy, whereas drinking during the second 6-week period was predicted by both subjective estimations of sleep and rapid eye movement sleep latency., Conclusion: Greater subjective accuracy of wakefulness at night provided by the patient predicted drinking during the study. Unlike nonalcoholic insomniacs, this alcoholic sample significantly underestimated WASO compared with PSG values. The predictive ability of sleep parameters depended on the selected measure of drinking outcomes and when outcomes were measured. Subjective sleep measures were better predictors of future drinking than corresponding PSG measures.

Subject Objective: To evaluate age and sex differences in sleep macroarchitecture in children and adolescents with major depressive disorder., Design: Ninety-seven (50 F, 47 M) symptomatic unmedicated depressed outpatients were compared with 76 healthy controls (42 F, 34 M) matched for age and sex., Setting: Participants spent 2 consecutive nights in the sleep laboratory., Participants: One hundred seventy-three children and adolescents, aged 8 to 18 years., Measurements and Results: Significant group-by-age-by-sex interactions were evident for total sleep period, percentage of Stage 1 sleep, percentage of Stage 2, percentage of slow-wave sleep, and rapid eye movement (REM) sleep latency. The depressed adolescent boys had the greatest sleep disturbance with the highest amount of percentage of Stage 1 sleep, the shortest REM latency, and the least percentage of slow-wave sleep and number of minutes of slow-wave sleep in the first non-REM period. There were minimal age differences in sleep parameters between depressed children and adolescent girls. Within age groups, the sex differences were minimal in the healthy controls. The sex differences within the depressed group were substantially larger than controls., Conclusions: These findings suggest a differential developmental influence on sleep in early-onset depression that is heavily dependent on sex. Sex differences are substantially smaller in healthy individuals compared with those with depression, in agreement with previous studies in depressed adults.

Previous work has indicated that low temporal coherence of ultradian sleep EEG rhythms is characteristic of depressed patients and women in particular. It may also be evident in depressed children and adolescents, although most published studies are limited in sample size. The present study evaluated temporal coherence of sleep EEG rhythms in 173 children and adolescents 8-17 years of age, including 97 who met criteria for major depressive disorder (MDD) and were symptomatic but unmedicated at the time of study and 76 healthy controls. Temporal coherence of all-night sleep EEG rhythms was evaluated on the second of two nights in the laboratory. Data were coded for diagnostic group, gender and age and subjected to MANOVAs. Temporal coherence was significantly lower in adolescents with MDD, compared to healthy controls. Findings were most robust for coherence between left and right beta and between delta and beta in both hemispheres. Both gender and age strongly influenced between-group differences, with the lowest temporal coherence among MDD girls, even in those under 13 years of age. In conclusion, early onset depression is associated with a reduction in synchronization of sleep EEG rhythms that shows a differential maturational course in boys and girls.

Previous studies indicate that high frequency power (>20Hz) in the electroencephalogram (EEG) are associated with feature binding and attention. It has been hypothesized that hallucinations and perceptual abnormalities might be linked to irregularities in fast frequency activity. This study examines the power and distribution of high frequency activity (HFA) during sleep in healthy control subjects and unmedicated patients with schizophrenia and depression. This is a post-hoc analysis of an archival database collected under identical conditions. Groups were compared using multivariate analyses of covariance (MANCOVA) using group frequency by stage analysis. A multiple regression analyzed the association between HFA power and clinical symptoms. Schizophrenic (SZ) and major depressive disorder (MDD) patients showed significantly greater high frequency (HF) power than healthy controls (HC) in all sleep stages (p<0.0001). SZs also exhibited significantly greater HF power than MDD patients in all sleep stages except wakefulness (W) (p<0.05). In all groups, gamma (35-45Hz) power was greater in W, decreased during slow wave sleep (SWS) and decreased further during rapid eye movement (REM). Beta 2 (20-35 Hz) power was greater in W and REM than in SWS. Only positive symptoms exhibited an association with HF power. Elevated HFA during sleep in unmedicated patients with SZ and MDD is associated with positive symptoms of illness. It is not clear how HFA would change in relation to clinical improvement, and further study is needed to clarify the association of HFA to the state/trait characteristics of SZ and MDD.

Objective: Sleep disturbances are strongly associated with mood disorders, although the majority of data have been obtained in patients with major depressive disorder. Studies reporting results in bipolar disorder are few, and results have not been consistent. Clozapine is a prototype of atypical antipsychotics, which is effective in improving symptoms of manic episodes in patients with bipolar disorder, or schizoaffective disorder, bipolar type and has been shown to influence sleep in other psychiatric disorders. The present study evaluated the sleep effects of clozapine in bipolar and schizoaffective disorders., Methods: Participants were 11 women and 4 men (range:28-53 years of age, mean 40.9+/-8.6 years), all with a history of mania by DSM-IV criteria for either bipolar I disorder or schizoaffective disorder, bipolar type. They participated in a sleep study at baseline and again after 6 months initiation of clozapine add-on therapy., Results: Sleep latency was longer on clozapine and the number of awakenings were increased, whereas time in bed (TIB) and total sleep period (TSP) were increased (range: F=6.2-17.9; df=l,12; p<0.05). Although none of the individual sleep stage showed significant treatment changes, both Stage 2 and slow-wave sleep were increased and Stage 2 decreased on clozapine. Subjective sleep measures improved on clozapine with a small but significant improvement in how rested patients felt upon awakening (t=-2.1; df=26; p<0.05)., Conclusion: Clozapine prolonged sleep latency, improved restedness, and increased total sleep time. Although lack of a control group limits interpretation of these results, they are in general agreement with studies in other psychiatric populations, and support the view that clozapine is primarily a NREM sleep enhancer. The improvement in restedness may be of positive clinical consequence.

Purpose: To test the hypothesis that subtle abnormalities of the autonomic nervous system underlie the chronic symptoms reported by many Gulf War veterans, such as chronic diarrhea, dizziness, fatigue, and sexual dysfunction., Methods: Twenty-two ill Gulf War veterans and 19 age-, sex-, and education-matched control veterans underwent measurement of circadian rhythm of heart rate variability by 24-hour electrocardiography, ambulatory blood pressure recording, Valsalva ratio testing, sympathetic skin response evaluation, sweat imprint testing, and polysomnography. Investigators were blinded to case- or control-group status., Results: High-frequency spectral power of heart rate variability increased normally 2.2-fold during sleep in controls but only 1.2-fold in ill veterans (P <0.0001). In ill veterans as compared with controls, it was lower at night (P = 0.0006), higher during the morning (P = 0.007), but no different during the rest of the day (P = 0.8). The mean heart rate of ill veterans also declined less at night (P = 0.0002), and their corrected QT intervals tended to be longer over the full 24 hours (P = 0.07), particularly at night (P = 0.03). Blunting of the nocturnal heart rate dip in ill veterans was confirmed by 24-hour automatic ambulatory blood pressure monitoring (P = 0.05) and polysomnography (P = 0.03). These differences remained significant after adjusting for potential confounders. Cases and controls were similar on measures of sympathetic adrenergic and sudomotor function, sleep architecture, respiratory function, and circadian variation in blood pressure and body temperature., Conclusion: Some symptoms of Gulf War syndrome may be due to subtle autonomic nervous system dysfunction.

Objective: To quantify circadian rhythms in rest-activity cycles in depressed children and adolescents., Method: Rest-activity cycles were evaluated by actigraphy over five consecutive 24-hour periods in 100 children and adolescents, including 59 outpatients with major depressive disorder (MDD) and 41 healthy normal controls. Total activity, total light exposure, and time spent in light at more than 1,000 lux were averaged over the recording period for each participant. Time series analysis was used to determine the amplitude and period length of circadian rhythms in rest-activity., Results: Overall, adolescents with MDD had lower activity levels, damped circadian amplitude, and lower light exposure and spent less time in bright light than healthy controls. Among children, those with MDD showed lower light exposure and spent less time in bright light, but only depressed girls showed damped circadian amplitude. The sex differences were substantially greater in the MDD group than in the normal control group., Conclusions: These results confirm damped circadian rhythms in children and adolescents with MDD and highlight the influence of gender and age on these measures.

Purpose: Chronic fatigue syndrome (CFS) is characterized by profound fatigue accompanied by disturbances of sleep, cognition, mood, and other symptoms. Our objective was to describe sleep architecture in CFS-discordant twin pairs., Methods: We conducted a co-twin control study of 22 pairs of monozygotic twins where one twin met criteria for CFS and the co-twin was healthy. Twins underwent two nights of polysomnography., Results: The percentage of Stage 3 and REM sleep was greater among the CFS twins than their healthy co-twins (P< or = .05 for both), but no other differences in sleep architecture including sleep latency, REM latency, and total sleep time were observed. Compared to their co-twins, CFS twins had higher values for the apnea-hypopnea index and apnea-hypopnea arousal index (P< or =.05 for both)., Conclusion: These results do not provide strong evidence for a major role for abnormalities in sleep architecture in CFS. Respiration appears impaired in CFS, but these clinical abnormalities cannot alone account for the prominence of sleep complaints in this illness. The co-twin control methodology highlights the importance of selecting well-matched control subjects.

Objective: The present study evaluated the effects of vagus nerve stimulation (VNS) on sleep in seven treatment-resistant depressed outpatients., Methods: Sleep studies were conducted in the laboratory at baseline and 10-12 weeks after VNS implantation while the concomitant psychotropic medication regimen was unchanged. Standard sleep macroarchitecture based on visual stage and assessment of ultradian sleep electroencephalographic (EEG) rhythms were measured on all nights., Results: An overall significant treatment effect on sleep macroarchitecture was obtained by MANOVA. Decreased awake time, decreased Stage 1 sleep and increased Stage 2 sleep were evident post-VNS, although univariate analyses did not reach significance. In addition, the strength or amplitude of ultradian sleep EEG rhythms more than doubled on VNS and was restored to within normal range., Conclusion: VNS improved the clinical symptoms of depression and sleep architecture. Results suggest that treatment-resistant depressed patients have dampened sleep EEG rhythms that are restored to near-normal amplitudes with VNS treatment.

Study Objectives: To examine the objective and subjective measures of insomnia in chronic fatigue syndrome (CFS)., Design: Monozygotic co-twin control study., Setting: Academic medical center., Patients or Participants: Twenty-two pairs of monozygotic twins where 1 member of the pair had CFS and the other did not., Interventions: N/A., Measurements and Results: Twenty-two CFS-discordant twin pairs completed a Sleep Disorders Questionnaire, overnight polysomnography, and a postpolysomnography sleep survey. Mean and percent differences in the sleep measures were compared between the CFS and healthy twins using matched-pair methods of analysis. Compared with their healthy co-twins, the CFS twins more frequently endorsed 8 subjective measures of insomnia and poor sleep (all p < or = 0.05). However, the CFS and healthy twins did not differ in objective polysomnographic measures of insomnia, including sleep latency, total sleep time, sleep efficiency, arousal number, arousal index, hypnogram awakenings, rapid eye movement (REM)-sleep latency, and percent stages 1, 2, and 3-4 (delta). Percent stage REM sleep was increased in the CFS twins compared with the healthy twins (27.7% vs. 24.4%, p < or = 0.05). On the postpolysomnography survey, CFS twins reported that they had slept fewer hours (6.2 vs. 6.7; p < or = 0.05), and were less well rested (p < or = 0.001) compared to their co-twins., Conclusions: CFS patients had worse subjective sleep than their co-twins despite little objective data supporting this discrepancy, suggesting they suffer from an element of sleep-state misperception. The higher percentage of REM sleep in the CFS twins implies that REM sleep may play a role in this illness.

This article reviews human and animal studies in the neurobiology of depression. The etiology of the illness, associated neurotransmitter dysregulation, sex steroids, the role of stress, and sleep regulation are discussed. It is suggested that the genesis of depression is related to homeostatic maladaptation that is sexually dimorphic. The authors propose that depressed females are hyperresponsive to stress, whereas depressed males are hyporesponsive to stress. This divergence reflects the exaggeration of naturally occurring differences between males and females, which are most obvious under challenge conditions. The authors conclude that future work in this area should fully evaluate sexual dimorphism, neural plasticity, critical periods, and individual differences in vulnerability.

Although polysomnographic abnormalities are prevalent in adults with major depressive disorders (MDD), the findings in children and adolescents have been more equivocal. Polysomnographic measures may be of predictive value in assessing course of illness. The present study used standard sleep measures and temporal coherence of sleep electroencephalogram (EEG) rhythms to predict recovery and recurrence in a 1-yr naturalistic follow-up in 47 children and adolescents 8-18 yr of age with MDD. Standard sleep measures did not predict clinical course. On the other hand, temporal coherence measures discriminated between those who recovered, recovered but recurred, and those who did not recover from the index episode. Specifically, coherence between beta, theta and delta recorded in the right hemisphere was significantly lower in the no-recovery group. In addition, temporal coherence was strongly associated with both time to recovery and recurrence. Those with the lowest coherence were less likely to recover or recurred sooner. Significant sex differences were found with a stronger relationship between temporal coherence and clinical course in boys. This study supports the use of quantitative sleep EEG measures as a predictor of clinical course in depression.

Study Objectives: To evaluate the effects of oral contraceptives (OCs) on sleep EEG in healthy women and in those with major depressive disorders (MDD)., Design: This archival study selected participants who had sleep EEG measured over two consecutive nights, following a five-day regularized sleep-wake routine. Between-groups multivariate analysis of variance (MANOVA) contrasted group and OC main effects and interactions on sleep architecture., Setting: N/A PARTICIPANTS: Sixty-eight women (ages 14-46 years) diagnosed with major depressive disorder (MDD), 13 of whom were on OCs and 55 were not. Patients were symptomatic and untreated at the time of study. Thirty-seven healthy control women (ages 12-46 years), nine of whom were on OCs and 28 were not., Interventions: N/A Measurements and Results: OC main effects were found for %SW and for REM latency. Significant OC x Group interactions were found for sleep latency and %REM. Sleep latency was significantly shorter on OCs, but only in healthy women. Women on OCs showed a shorter REM latency, more total REM time, and less slow-wave sleep than women who were not on OCs., Conclusions: The effects of OCs were generally larger in healthy women than in those with MDD. Moreover, OC use was associated with more disturbed sleep in healthy women. These findings imply that OC use may compromise sleep EEG differences between healthy and depressed women and may be more difficult to differentiate between depressed patients and healthy controls when sleep studies include women on OCs. These findings may also have implications for evaluating gender differences in sleep architecture.

Background: Previous work has indicated that low temporal coherence of ultradian sleep electroencephalographic rhythms is characteristic of depressed patients and of depressed women, in particular. It may also be evident in one quarter of those at high risk, based on a family history of depression., Methods: The present study evaluated temporal coherence of sleep electroencephalographic rhythms in 41 adolescent girls with a maternal history of depression (high risk) and 40 healthy controls (low risk). The entire sample was followed clinically every 6 months for 2 years., Results: Temporal coherence was significantly lower among the high-risk girls than in controls. Regression analyses predicted group from coherence values and correctly classified 70% of the high-risk group with a false-positive rate of 5% among controls. Moreover, 54% of the high-risk girls were identified with extreme low coherence. On clinical follow up, 14 girls showed depressive symptoms, 9 in the high-risk group (22.5%) and 5 controls (12.2%). Six met DSM-IV criteria for first-episode major depressive disorder, five high-risk and one control. Most importantly, 41% of those identified as having the most abnormal coherence values either showed symptoms of depression or met diagnostic criteria upon follow up., Conclusions: Low temporal coherence is evident in adolescent girls at high risk for depression. The more abnormal the coherence, the greater the risk of a first episode of major depressive disorder within 2 years of sleep study, approximately 10 times greater than in controls.

Objective: To determine if there are significant differences in the temporal organization of rapid eye movement (REM) sleep microarchitecture between healthy controls and outpatients with major depressive disorder (MDD)., Methods: Forty age-matched subjects, 20 men and 20 women, half with MDD, were selected from an archive of sleep electroencephalography (EEG) data collected under identical conditions. Each participant spent 2 consecutive nights in the Sleep Study Unit of the University of Texas Southwestern Medical Center at Dallas, the first of which served as adaptation. The average amplitude in each of 5 conventional EEG frequency bands was computed for each REM period across the second night. Data were then coded for group and sex., Results: Aside from REM latency, none of the key sleep macroarchitectural variables differentiated MDD patients from controls. REM latency was longest in men with MDD. Sleep microarchitecture, however, did show a number of between-group differences. In general, slower frequencies declined across REM periods, with a significant REM period effect for delta, theta and alpha amplitude. Group x sex interactions were also obtained for theta and alpha. Beta activity showed a unique temporal profile in each group, supported by a significant REM period x group x sex interaction. In addition, the temporal change in theta amplitude across REM periods was most striking in women with MDD., Conclusions: This study suggests that, like during non-REM sleep, EEG amplitude shows a systematic temporal change over successive REM sleep periods and also shows elements that are both disease- and sex-dependent.

Adults with major depressive disorder (MDD) demonstrate certain sleep polysomnographic abnormalities, including sleep continuity disturbances, reduced slow-wave sleep, shortened rapid eye movement (REM) latency, and increased REM density. Findings of sleep EEG studies in depressed children and adolescents have yielded conflicting results, possibly because of methodological variations across the studies. Generally, however, studies have demonstrated that depressed children and adolescents exhibit less sleep continuity and non-REM sleep differences in comparison with control subjects than do adults. Thus, results from adult sleep polysomnography studies cannot necessarily be generalized to children and adolescents. Depressed adults who have reduced REM latency during the symptomatic episode appear more likely to have a relapse once treatment is discontinued than those with normal REM latency. No studies of the relationship between sleep polysomnographic variables and clinical course have been reported in depressed children and adolescents. Data for baseline clinical variables and 3 nights of sleep polysomnography were examined in 113 depressed children (< or = 12 yr; n = 51) and adolescents (> or = 13 yr; n = 62) (56 in-patients and 57 outpatients) where data was available on at least 1 yr of naturalistic follow-up. Subjects came from 2 studies of sleep polysomnography in children and adolescents with MDD. Clinical course was assessed using the Kiddie-Longitudinal Interval Follow-Up Evaluation (K-LIFE). This interview was used to define recovery from the index episode of MDD and recurrence, a new episode of meeting full criteria for MDD. Clinically, within 1 yr of initial evaluation 102/113 subjects had recovered from their index episode of depression (minimal or no symptoms for 60 d). Of the 102 subjects who recovered, 36 (35.3%) had a recurrence of MDD. The majority of subjects (55%) who had a recurrence were not on medication at the time of recurrence. Subjects who had a recurrence were more likely to report suicidal thoughts or attempts at baseline compared to those without a recurrence (67 vs. 37%; F = 8.77; p = 0.004). On baseline sleep polysomnography, subjects with a later recurrence had decreased sleep efficiency and delayed sleep onset (sleep latency > 10 min). Probability of recurrence at 12 months was 0.39 compared to 0.15 in subjects with non-delayed sleep onset (p = 0.005). Baseline suicidal ideation and sleep dysregulation on sleep polysomnography predicted recurrence in a large sample of depressed children and adolescents. Depression in children and adolescents is frequently a chronic, recurrent illness. Factors that can predict clinical course are important in increasing our understanding of depression in this age group.

Despite clear evidence of an intimate connection between sleep, major depressive disorders (MDD) and gender, few studies have explored gender differences in either sleep or in wakefulness in patients as a means of better understanding the psychogenic components of MDD. Indeed, few sleep studies focus on characterising gender differences in any population. This paper will present a review of the literature on gender differences in sleep and depression. The theoretical and clinical implications of the findings will also be discussed. The premise of the present review is that there is an inherent increased vulnerability to depression in women that arises out of basic gender differences in brain organisation and state regulation, particularly in response to a "biological challenge" during sleep. It is argued that the inherent properties of organisation and regulation of sleep EEG in healthy men and women, elicited under challenge conditions, show gender-specific vulnerability to organisational abnormalities that model homeostatic abnormalities in depressed men and women and contribute to the genesis of depression. 2001 Harcourt Publishers Ltd

New members of the extended MHC class I-like family were identified based on their ability to bind human cytomegalovirus glycoprotein UL16 and/or their mutual homology. Soluble UL16 binding proteins (ULBP) competed with each other for binding to NK cells. Treatment of human and mouse NK cells with ULBP led to increased production of cytokines/chemokines, proliferation, cytotoxic activity and up-regulation of activation-associated surface molecules. The presence of ULBP during the stimulation phase of the CTL assay caused increased cytotoxic activity. Addition of soluble recombinant UL16 protein inhibited the biological activities mediated by ULBP, suggesting the existence of a novel mechanism utilized by CMV to evade elimination by the host immune system.

Background: Quantitative EEG studies have identified a number of sleep abnormalities in adults with major depressive disorders (MDD), including a reduction in the amplitude of delta activity during NREM sleep. To date, these methodologies have not been used in early onset MDD., Methods: Delta activity during NREM sleep was compared in eight symptomatic but unmedicated adolescent females with MDD and eight age- and gender-matched healthy controls., Results: The depressed group showed significantly lower delta amplitude and power in the first NREM sleep period. By contrast, standard sleep architecture did not differentiate between groups., Limitations: Given the sample size, this study is best viewed as tentative. In addition, it has yet to be determined whether adolescent males with MDD also show delta sleep abnormalities. Further, failure to find between-group differences in REM latency or other macroarchitectural measures may be due to the small sample size., Conclusions: The findings of this study underscore the utility of quantitative sleep EEG techniques in early onset MDD. The results of the present study do, however, diverge from reports in adults with MDD, where delta abnormalities are more prevalent in men. Such findings suggest that the maturational time course of sleep EEG disturbances may differ for males and females with depression. Early emergence of delta abnormalities in depression may be of relevance to clinical course of illness.

The human cytomegalovirus glycoprotein, UL16, binds to two members of a novel family of molecules, the ULBPs, and to the MHC class I homolog, MICB. The ULBPs are GPI-linked glycoproteins belonging to the extended MHC class I family but are only distantly related to MICB. The ULBP and MICB molecules are ligands for the activating receptor, NKG2D/DAP10, and this interaction is blocked by a soluble form of UL16. The ULBPs stimulate cytokine and chemokine production from NK cells, and expression of ULBPs in NK cell-resistant target cells confers susceptibility to NK cell cytotoxicity. Masking of NK cell recognition of ULBP or MIC antigens by UL16 provides a potential mechanism by which human cytomegalovirus-infected cells might evade attack by the immune system.

This paper reviews sleep disturbances in patients with major depressive disorders and the effects of different classes of antidepressants on sleep. It is clear from the studies reviewed that not all antidepressants improve sleep, and, indeed, some worsen sleep disturbances in patients with depression. Whether sleep is improved or further disrupted is of high clinical significance, because persistent sleep problems elevate the risk of relapse, recurrence, or suicide, as well as the need for augmenting medications.

Both major depressive disorders (MDD) and schizophrenia (SZ) have been associated with reductions in slow-wave (Stages 3 and 4) sleep, although these findings are controversial. The present study compared quantitative EEG measures of slow-wave activity (0.5-4 Hz) during non-REM (NREM) sleep among age-matched, symptomatic but unmedicated, depressed, schizophrenic and healthy control men (n=13/group). The amplitude of slow-wave activity (SWA) in the first NREM sleep period was significantly lower in both the MDD and SZ groups compared with controls. However, the time course of SWA, its accumulation and dissipation over all NREM sleep time, was abnormal in the MDD group but not in those with SZ. These findings suggest that the regulation of SWA is impaired in men with MDD but not in SZ. Thus, although those with SZ show reduced amplitude SWA in the first NREM period, there is no evidence that homeostatic regulation of SWA is impaired in this psychiatric group.

The amplitude and time course of slow-wave activity (SWA) during NREM sleep were compared in 76 outpatients with depression and 55 healthy control subjects. Lower SWA amplitude was evident in the depressed group, especially among depressed men. For the most part, significant differences between patients and control subjects were restricted to the first NREM period and only in those 20-30 years of age. Significant age-related declines in SWA amplitude were evident in control subjects but not in depressed patients. In addition, sex differences in the depressed group were twice as large as those seen in control subjects. The time course of SWA amplitude, presumed to reflect homeostatic sleep regulation of SWA, was only abnormal in depressed men with lower accumulation and slower dissipation over NREM sleep. Depressed women showed no evidence of an abnormal SWA time course. Furthermore, no sex differences in the time course of SWA were evident in control subjects, and age-related changes in this aspect of regulation were not striking in any group. Thus, the amplitude of SWA showed strong age effects in healthy individuals but not in those with MDD whereas the time course showed very subtle age effects. It was suggested that men, but not women, with MDD show impaired SWA regulation that is evident from 20 to 40 years of age. These findings provide further support that the pathophysiology of depression differs for men and women and suggest that maturational effects on SWA in depression differ from those observed in healthy individuals.

Study Objectives: The primary aim was to evaluate group and sex differences in delta activity across non-rapid eye movement (NREM) sleep in depressed patients and healthy controls., Design: Repeated-measures ANOVA contrasted delta power, amplitude and incidence in the first three NREM periods (stages 2, 3, and 4) of sleep. The time course of delta activity was evaluated with exponential regressions. Age effects on delta were evaluated with linear regression analysis., Setting: Two consecutive nights were spent in the laboratory, the first of which served as adaptation., Patients or Participants: Twenty-two (9 men, 13 women) symptomatic, but unmedicated, outpatients with major depressive disorder (MDD) and 23 healthy controls (15 men, 8 women) participated in the study., Measurements and Results: Delta power and amplitude showed significant group by sex interactions. Men with MDD showed lower power and amplitude in NREM sleep compared to women with MDD, but did not differ significantly from controls. However, the time course of delta power and amplitude was significantly different in men with MDD, with lower accumulation and slower dissipation across NREM sleep than all other groups. Women with MDD showed no evidence of lower delta power and amplitude or an abnormal time course compared to control women or men. Age had a differential influence on delta activity between the groups, with little age-related change in delta activity in the depressed groups., Conclusions: It was concluded that slow-wave sleep deficiencies may be characteristic of men, but not women, with MDD. It was also concluded that the influence of age on delta activity varied as a function of both psychiatric status and sex.

Background: Sleep electroencephalographic (EEG) studies of individuals with major depressive disorder have identified several microarchitectural features associated with the illness. These abnormalities are also found in clinically remitted individuals, raising the question of whether they are vulnerability markers of depression. This study evaluated the sleep EEG in high-risk individuals to see if abnormalities are present in the sleep EEG prior to the onset of illness., Methods: A total of 26 subjects (13 males and 13 females) were recruited for study on the basis of 1) having a parent or grandparent treated for major depressive or bipolar affective disorder and 2) having no history of personal psychiatric illness. Polysomnographic data were collected and compared with gender- and age-matched healthy control subjects with no personal or family history of psychiatric illness. The primary outcome measures were interhemispheric and intrahemispheric coherence., Results: Period analysis of the sleep EEG showed that beta-delta coherence was lower bilaterally in male high-risk subjects. Right-hemispheric theta-delta coherence was also lower in male high-risk subjects, with female high-risk subjects evidencing lower beta coherence., Conclusions: Sleep-EEG abnormalities associated with major depressive disorder are present in never mentally ill individuals at high risk for the illness. These markers may be useful in the prediction of illness and in family genetic studies of mood disorders.

Background: It has been suggested that a primary ultradian (80-120 minute) rhythm disturbance in EEG underlies sleep abnormalities in adults with depression. The present study evaluated ultradian rhythm disturbances in childhood and adolescent depression., Methods: Sleep macroarchitecture and temporal coherence in quantitative EEG rhythms were investigated in 50 medication-free outpatients with major depression (25 children and 25 adolescents) and 15 healthy normal controls (5 children and 10 adolescents)., Results: Few of the macroarchitectural measures showed significant group effects. In fact, age and sex effects were stronger than disease-dependent components. Temporal coherence of EEG rhythms during sleep did differentiate those with MDD from controls. Both depressed children and adolescents had lower intrahemispheric coherence, whereas interhemispheric was only lower in depressed adolescents in comparison with controls. Gender differences were evident in adolescents, but not children, with MDD with lowest interhemispheric coherence in adolescent girls., Conclusions: These findings are in keeping with increased risk for depression in females beginning at adolescence and extending throughout adulthood. It was suggested that low temporal coherence in depression reflects a disruption in the fundamental basic rest-activity cycle of arousal and organization in the brain that is strongly influenced by gender.

A wide range of studies have been published over the past two decades that involve the intersection of sleep EEG, insomnia, psychiatric illness (especially depressive disorders) and psychopharmacology. Much of value has been discovered, but there have also been false starts and contradictory results. There is in fact strong evidence that insomnia is associated with medical and psychiatric illness and that the sleepiness associated with insomnia is the cause of many accidents. Thus, the direct (visits to doctors, cost of sleeping medication, complications from use of these medications) and indirect (accidents, quality of life) costs of insomnia are enormous and constitute a major public health problem in the industrialized countries. Believing that it is now timely to assess the state of this important research area, a consensus conference was convened on June 26-28, 1998, in Porto Cervo (Italy) to attempt to clarify the important issues and findings on the clinical effect of the different classes of antidepressant drugs on sleep quality in depression. The participants' consensus on some of the main topics is presented with the hope that this discussion and analysis will contribute to productive research in this important field., (Copyright 2000 S. Karger AG, Basel)

Background: Recent studies have suggested that major depressive disorders are associated with a breakdown in the organization of ultradian rhythm in sleep EEG. The present study used cross-spectral analysis of sleep EEG to confirm this finding, in a larger-scale study, evaluating the influence of gender and age on ultradian rhythms in depression., Methods: Temporal coherence of ultradian (80-120 min) rhythms in beta, theta and delta, recorded from central and parietal sites, were compared in 120 symptomatic, unmedicated, depressed outpatients and 59 healthy normal controls., Results: Few macro-architectural differences were noted between patients and controls. However, interhemispheric beta and theta coherence and intrahemispheric coherence between beta and delta rhythms were significantly lower in depressed patients. Coherence measures were lowest in women with depression and highest in men in the control group, but were not strongly influenced by age. Over 65% of depressed patients were > or = 2 standard deviations below normal on at least one coherence measure, in sharp contrast to less than 10% of patients on macro-architectural variables., Conclusions: It was concluded that dysregulation of ultradian rhythms characterizes the majority of depressed out-patients, primarily women, even when macro-architecture did not differentiate groups. The outcome of this study supports the view that the pathophysiology of depression is strongly influenced by gender. It was suggested that low temporal coherence in depression reflects a breakdown in the organization of sleep EEG rhythms within and between the two hemispheres.

The present article reviews direct and indirect evidence of the effects of sex steroids on different aspects of sleep. It begins with a review of what is known about the effects of steroid hormones on sleep and on central nervous system processes related to sleep, such as the GABA-ergic system, in animals. It continues with a review of the effects of exogenous hormones on human sleep and a review of studies comparing sleep during hypogonadal states secondary to surgical or natural menopause. The article proceeds to review the data on the effects of the menstrual cycle on both subjective and objective aspects of sleep and circadian temperature and melatonin rhythms in samples of healthy women, women with premenstrual dysphoric disorder, and women with primary insomnia. Then, the article reviews gender differences in sleep during depression and raises the possibility that sex steroids moderate these differences. Finally, the article concludes with a discussion of the implications of the data reviewed for basic clinical, and methodological aspects of sleep research.

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

The vitronectin receptor, alphavbeta3 integrin, plays an important role in tumor cell invasion, angiogenesis, and phagocytosis of apoptotic cells. CD47, a member of the multispan transmembrane receptor family, physically and functionally associates with vitronectin receptor (VnR). Although vitronectin (Vn) is not a ligand of CD47, anti-CD47 and beta3 mAbs suppress Vn, but not fibronectin (Fn) binding and function. Here, we show that anti-CD47, anti-beta3 mAb and Vn, but not Fn, inhibit sCD23-mediated proinflammatory function (TNF-alpha, IL-12, and IFN-gamma release). Surprisingly, anti-CD47 and beta3 mAbs do not block sCD23 binding to alphav+beta3+ T cell lines, whereas Vn and an alphav mAb (clone AMF7) do inhibit sCD23 binding, suggesting the VnR complex may be a functional receptor for sCD23. sCD23 directly binds alphav+beta3+/CD47(-) cell lines, but coexpression of CD47 increases binding. Moreover, sCD23 binds purified alphav protein and a single human alphav chain CHO transfectant. We conclude that the VnR and its associated CD47 molecule may function as a novel receptor for sCD23 to mediate its proinflammatory activity and, as such, may be involved in the inflammatory process of the immune response.

This paper briefly reviews the effects of antidepressants on sleep, and highlights recent studies on the effects of nefazodone on sleep in healthy adults and those with major depressive disorders. Studies indicate significant improvement in sleep quality, decreased light sleep, and a reduction in nocturnal awakenings on nefazodone with minimal effect on REM sleep. The clinical relevance of these sleep findings is also discussed.

Background: Sleep disturbances are common in major depressive disorder. In previous open-label trials, nefazodone improved sleep continuity and increased rapid eye movement (REM) sleep, while not affecting stage 3/4 sleep or REM latency: in contrast, fluoxetine suppressed REM sleep. This study compared the objective and subjective effects of nefazodone and fluoxetine on sleep., Methods: This paper reports combined results of three identical, multisite, randomized, double-blind, 8-week, acute-phase trials comparing nefazodone (n = 64) with fluoxetine (n = 61) in outpatients with nonpsychotic major depressive disorder and insomnia. Sleep electroencephalographic (EEG) recordings were gathered at baseline and weeks 2, 4, and 8. Clinical ratings were obtained at weeks 1-4, 6, and 8., Results: Nefazodone and fluoxetine were equally effective in reducing depressive symptoms; however, nefazodone differentially and progressively increased (while fluoxetine reduced) sleep efficiency and reduced (while fluoxetine increased) the number of awakenings in a linear fashion over the 8-week trial. Fluoxetine, but not nefazodone, prolonged REM latency and suppressed REM sleep. Nefazodone significantly increased total REM sleep time. Clinical evaluations of sleep quality were significantly improved with nefazodone compared with fluoxetine., Conclusions: Nefazodone and fluoxetine were equally effective antidepressants. Nefazodone was associated with normal objective, and clinician- and patient-rated assessments of sleep when compared with fluoxetine. These differential sleep EEG effects are consistent with the notion that nefazodone and fluoxetine may have somewhat different modes and spectra of action.

Purpose: CD30 ligand (CD30L), which is expressed on resting B and activated T lymphocytes, can induce cell death in several CD30+ cell lines. Patients with CD30+ tumors (Hodgkin's disease and Ki-1+ non-Hodgkin's lymphoma) frequently have elevated soluble CD30 (sCD30) levels in their serum, which correlates with a poor prognosis. The role of sCD30 in protecting tumor cells from CD30L-mediated cell death and the pattern of CD30L expression on human peripheral-blood lymphocytes (PBLs) of normal donors and patients with CD30+ tumors are investigated., Materials and Methods: CD30L surface protein expression was determined by two-color flow cytometry on PBLs of patients with CD30+ tumors and normal individuals. CD30L levels were determined on subsets of PBLs before and after stimulation with phytohemagglutinin (PHA), anti-CD3 antibody, or CD40L. sCD30 was measured by enzyme-linked immunosorbent assay (ELISA). The apoptotic activity of membrane-bound CD30L was tested in a CD30+ cell line by the annexin V-binding method., Results: Unstimulated T lymphocytes of normal donors and patients with lymphoma rarely expressed CD30L surface protein, but were able to express it after stimulation with PHA or anti-CD3 antibody. Resting B cells of patients with CD30+ tumors had lower levels of detectable surface CD30L compared with normal donors (mean, 55% and 80.6%, respectively; P = .0008). Patients with high levels of serum sCD30 had lower detectable levels of CD30L on their PBLs (R2 = .72, P = .0008) and exogenous sCD30 blocked membrane-bound CD30L-mediated apoptosis in a CD30+ cell line., Conclusion: In patients with CD30+ tumors, sCD30 can decrease the availability of CD30L on PBLs. Blocking the apoptosis-inducing activity of CD30L by its soluble receptor may explain how CD30+ tumors escape immunosurveillance and may be related to the reported poor prognosis of patients who have elevated sCD30 levels.

Fluoxetine is associated with substantial objective and subjective sleep disturbance in adults with major depressive disorders. In this preliminary report, the effects of fluoxetine on sleep electroencephologram (EEG) are described in 6 children and adolescents with nonpsychotic major depression. Fluoxetine increased light Stage 1 sleep, the number of arousals and rapid eye movement (REM) density. REM latency was largely unaffected. Oculomotor abnormalities were also evident on treatment, accompanied by an increase in myoclonic activity. Subjective sleep was also disturbed on treatment. These results are in keeping with those observed in depressed adults treated with fluoxetine.

This study was an 8-week, randomized, double-blind, parallel-group investigation that compared the effects of nefazodone and fluoxetine on sleep architecture and on clinician- and patient-rated sleep measures in 43 outpatients with moderate to severe, nonpsychotic major depressive disorder and insomnia. Twenty-two patients received nefazodone 200 mg daily for 1 week, followed by 400 mg daily for 7 weeks. Twenty-one patients received fluoxetine 20 mg daily. Dosage increases (to 500 mg/day for nefazodone and 40 mg/day for fluoxetine) were available after day 29, depending on clinician judgement. Sleep parameters were measured during baseline phase, while patients were unmeasured and symptomatic, and at weeks 2, 4, and 8 of treatment. Nefazodone and fluoxetine were equally effective as antidepressants. However, compared with baseline, nefazodone increased sleep efficiency and reduced the number of awakenings and percent awake and movement time, whereas fluoxetine increased the number of awakenings and did not significantly alter sleep efficiency or percent awake and movement time. Although fluoxetine increased stage 1 sleep and rapid eye movement (REM) latency and reduced total percent REM sleep, nefazodone increased REM sleep, decreased REM latency, and did not alter stage 1 sleep. Differences between treatment groups, based on change from baseline, revealed greater sleep efficiency, fewer awakenings, less percent awake and movement time, less percent stage 1 and more REM sleep, and shorter REM latency for nefazodone compared with fluoxetine. Significantly greater improvement in clinician- and patient-rated sleep disturbance was found with nefazodone compared with fluoxetine. Nefazodone was associated with better sleep quality.

Pichia pastoris is a yeast capable of expressing large amounts of some proteins. When expression vectors are introduced into P. pastoris, individual transformants typically express widely varying amounts of protein. Because clones expressing the highest level of protein occur infrequently during the transformation process, finding them can be very labor-intensive. We developed an immunological based filter screening method that rapidly detects transformants secreting large amounts of a heterologous protein. We have applied this method to the expression of a soluble trimeric form of CD40L, a molecule that regulates B-cell responses. Using this method, we identified transformants with one to 13 copies of the CD40L expression cassette. Maximum expression was obtained with clones containing eight or more copies of the expression cassette, and a clone with eight copies was selected for further analysis. High cell density fermentation of this clone using a mixed glycerol:methanol feed yielded 255 mg CD40L per liter of supernatant.