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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sleep is an active state that is critical for our physical, mental, and emotional well-being. Sleep is also important for optimal cognitive functioning, and sleep disruption results in functional impairment. Insomnia is the most common sleep disorder in psychiatry. At any given time, 50% of adults are affected with 1 or more sleep problems such as difficulty in falling or staying asleep, in staying awake, or in adhering to a consistent sleep/wake schedule. Narcolepsy affects as many individuals as does multiple sclerosis or Parkinson disease. Sleep problems are especially prevalent in schizophrenia, depression, and other mental illnesses, and every year, sleep disorders, sleep deprivation, and sleepiness add billions to the national health care bill in industrialized countries. Although psychiatrists often treat patients with insomnia secondary to depression, most patients discuss their insomnia with general care physicians, making it important to provide this group with clear guidelines for the diagnosis and management of insomnia. Once the specific medical, behavioral, or psychiatric causes of the sleep problem have been identified, appropriate treatment can be undertaken. Chronic insomnia has multiple causes arising from medical disorders, psychiatric disorders, primary sleep disorders, circadian rhythm disorders, social or therapeutic use of drugs, or maladaptive behaviors. The emerging concepts of sleep neurophysiology are consistent with the cholinergic-aminergic imbalance hypothesis of mood disorders, which proposes that depression is associated with an increased ratio of central cholinergic to aminergic neurotransmission. The characteristic sleep abnormalities of depression may reflect a relative predominance of cholinergic activity. Antidepressant medications presumably reduce rapid eye movement (REM) sleep either by their anticholinergic properties or by enhancing aminergic neurotransmission. Intense and prolonged dreams often accompany abrupt withdrawal from antidepressant drugs, a reflection of an REM rebound after drug-induced REM deprivation. The postulated link between sleep and psychiatric disorders has been reinforced by the findings of modern neurobiology.
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PMID:Sleep disorders in psychiatry. 1697 26

Neurons in the lateral hypothalamus (LH) that contain hypocretin/orexin have been established as important promoters of arousal. Deficiencies in the hypocretin/orexin system lead to narcolepsy. The inhibition of hypocretin/orexin neurons by sleep-promoting neurotransmitters has been suggested as one part of the sleep regulation machinery. Adenosine has been identified as a sleep promoter and its role in sleep regulation in the basal forebrain has been well documented. However, the effect of adenosine on arousal-promoting hypocretin/orexin neurons has not been addressed, despite recent evidence that immunocytochemical visualization of adenosine receptors was detected in these neurons. In this study, we examined the hypothesis that adenosine inhibits the activity of hypocretin/orexin neurons by using electrophysiological methods in brain slices from mice expressing green fluorescent protein in hypocretin/orexin neurons. We found that adenosine significantly attenuated the frequency of action potentials without a change in membrane potential in hypocretin/orexin neurons. The adenosine-mediated inhibition arises from depression of excitatory synaptic transmission to hypocretin/orexin neurons because adenosine depresses the amplitude of evoked excitatory postsynaptic potential and the frequency of spontaneous and miniature excitatory postsynaptic currents in these neurons. At the cell body of the hypocretin/orexin neurons, adenosine inhibits voltage-dependent calcium currents without the induction of GIRK current. The inhibitory effect of adenosine is dose dependent, pertussis toxin sensitive, and mediated by A1 receptors. In summary, our data suggest that in addition to its effect in the basal forebrain, adenosine exerts its sleep-promoting effect in the LH by inhibition of hypocretin/orexin neurons.
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PMID:Adenosine inhibits activity of hypocretin/orexin neurons by the A1 receptor in the lateral hypothalamus: a possible sleep-promoting effect. 1709 23

Low-resolution brain electromagnetic tomography (LORETA) showed a functional deterioration of the fronto-temporo-parietal network of the right hemispheric vigilance system in narcolepsy and a therapeutic effect of modafinil. The aim of this study was to determine the effects of modafinil on cognitive and thymopsychic variables in patients with narcolepsy and investigate whether neurophysiological vigilance changes correlate with cognitive and subjective vigilance alterations at the behavioral level. In a double-blind, placebo-controlled crossover design, EEG-LORETA and psychometric data were obtained during midmorning hours in 15 narcoleptics before and after 3 weeks of placebo or 400 mg modafinil. Cognitive investigations included the Pauli Test and complex reaction time. Thymopsychic/psychophysiological evaluation comprised drive, mood, affectivity, wakefulness, depression, anxiety, the Symptom Checklist 90 and critical flicker frequency. The Multiple Sleep Latency Test (MSLT) and the Epworth Sleepiness Scale (ESS) were performed too. Cognitive performance (Pauli Test) was significantly better after modafinil than after placebo. Concerning reaction time and thymopsychic variables, no significant differences were observed. Correlation analyses revealed that a decrease in prefrontal delta, theta and alpha-1 power correlated with an improvement in cognitive performance. Moreover, drowsiness was positively correlated with theta power in parietal and medial prefrontal regions and beta-1 and beta-2 power in occipital regions. A less significant correlation was observed between midmorning EEG LORETA and the MSLT; between EEG LORETA and the ESS, the correlation was even weaker. In conclusion, modafinil did not influence thymopsychic variables in narcolepsy, but it significantly improved cognitive performance, which may be related to medial prefrontal activity processes identified by LORETA.
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PMID:Low-resolution brain electromagnetic tomography (LORETA) identifies brain regions linked to psychometric performance under modafinil in narcolepsy. 1718 65

Modafinil, a medication for the excessive sleepiness associated with narcolepsy, has been hypothesized to improve not just alertness but mood as well. The purpose of this study was to determine how treatment with modafinil affects mood in healthy volunteers. Normal healthy volunteers (n = 12, 10 men and 2 women; 30-44 years) underwent a 3-day, counterbalanced, randomized, crossover, inpatient trial of modafinil (400 mg daily) versus placebo with 4-day washout period between 2 treatments. Mood was assessed daily using both the Positive and Negative Affect Schedule and a general mood scale, which consisted of 10 bipolar adjective ratings based on a severity scale ranging from 1 to 10. Modafinil increased general mood and Negative Affect scales relative to placebo and had a significant effect on Positive Affect scales. These results suggest that modafinil may have general mood-elevating effects accompanied by increased negative affect (anxiety). The findings may have implications for clinical practice, in particular for the adjunctive use of modafinil in treatment-resistant depression.
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PMID:A randomized, double-blind, crossover trial of modafinil on mood. 1722 18

Excessive daytime sleepiness (EDS) is a prevalent complaint among patients in psychiatric care. Patients with conditions of EDS have often been misdiagnosed with depression due to their complaints of lack of energy, poor concentration, memory disturbance, and a reduced interest in life. Impaired alertness associated with EDS can be detrimental to a person's quality of life by causing decreased work performance, self-consciousness, low self esteem, and social isolation. Excessive sleepiness is also associated with various health problems, comorbid medical and psychiatric conditions, and fatal accidents occurring after the driver has fallen asleep at the wheel. Contributing factors leading to EDS range from insufficient sleep hours to central nervous system-mediated debilitating hypersomnolence. Circadian rhythm disorders, sleep disorders such as obstructive sleep apnea and narcolepsy, and medications that cause sleepiness may also contribute to symptoms of EDS. Recognition of the symptoms of sleep deprivation is essential, as many such patients do not have a clear awareness of their own sleepiness. Treatment options, depending upon the condition, include light therapy or appropriate airway management techniques such as nasal continuous positive airway pressure (CPAP). Occasionally, wakefulness-promoting medications are necessary, particularly in patients with narcolepsy. In this expert roundtable supplement, Stephen P. Duntley, MD, reviews the definition and prevalence of EDS and discusses the contributing factors and consequences of daytime sleepiness. Next, Richard K. Bogan, MD, FCCP, gives an overview of the differential diagnosis of EDS and the assessment tools available for identifying sleepiness in symptomatic patients. Finally, Mary B. O'Malley, MD, PhD, reviews treatment of EDS, including counseling on sleep hygiene and duration of sleep, mechanical treatments, bright-light therapy, and wake-promoting medications.
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PMID:Recent advances in the treatment and management of excessive daytime sleepiness. 1727 17

Nasal continuous positive airway pressure (CPAP) is an effective treatment for most patients with obstructive sleep apnea syndrome (OSAS), improving sleepiness, cognitive function and mood. A number of patients, however, complain about persistent sleepiness after CPAP. In these cases another clinical history should be carried out to confirm the diagnosis of OSAS, to check CPAP compliance and to exclude associated conditions such as poor sleep hygiene, depression, narcolepsy or idiopathic hypersomnia. If necessary, a full polysomnography (PSG) followed by a multiple sleep latency test or even a full PSG with CPAP titration should be performed. Experimental data in animals suggest that long-term intermittent hypoxia related to the apneic events could deteriorate the brain structures that regulate alertness. This impairment, if present in humans, could be another reason for residual sleepiness after CPAP. Modafinil has been shown to reduce subjective sleepiness after CPAP in OSAS patients. Further studies are warranted to clarify the way in which CPAP modifies sleepiness.
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PMID:Persistent sleepiness in CPAP treated obstructive sleep apnea patients: evaluation and treatment. 1746 12

In 2003 were promulgated the texts regulating rest and safety, in the USA (approved by the ACGME) and in France (January 9th, 2001 and September 14th, 2001). The institution of the "rest for safety", an eleven hours duration interruption of activity, immediately after a night-call, can be viewed as a progress in the search for safety. Several studies showed a link between excessive work hours and occurrence of medical incidents related to tiredness. However published data do not show a link between tiredness and patients endangering. The tiredness resulting from sleep deprivation and disturbances in circadian rhythms is a cumulative phenomenon erased by a period of rest. In spite of a large individual variability, tiredness increases anxiety scores, irritability, depression and it deteriorates cognitive performances. The concept of "prophylactic" rest considers that a subject cannot start, rested, a work if he did not sleep at least 5 hours the previous night, or 12 hours during the previous 48 hours. The second important aspect of the rest for safety is the long-term prevention of potential pathologies in medical staff, in particular burnout syndrome. In our profession, night calls are considered most stressful; the psychological stress related to anticipation and night context causes measurable cardiovascular disturbances in anesthesiologists. Shift-work sleep disorders may induce gastric ulcers, heart attacks, metabolic syndrome, depression and accidents related to somnolence. Long duration work-hours, accompanied by sleep deprivation, may double the risk of car accidents in junior physicians, in whom vigilance levels can compare with those of patients concerned by narcolepsy or with the cognitive disturbances induced by alcohol intoxication. Reduced work-hours improve vigilance and divide by three the rate of serious medical errors. True opportunities of sleep and control of sleep duration at the individual level could be suggested. The idea that taking the necessary rest would be synonymous with a decrease of efficiency in patient care is not demonstrated, but the danger of a poorer information transmission should be handed with an optimization of our manpower and organization. Aging is accompanied by a progressive disorganization of sleep. The foreseeable shortage of manpower, synonymous with aging of the medical actors and increased vulnerability to tiredness, is a posteriori the justification of the institution of the rest for safety.
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PMID:[Rest for safety: which stakes?]. 1748 45

It has recently been reported that Parkinson's disease (PD) is preceded and accompanied by daytime sleep attacks, nocturnal insomnia, REM sleep behaviour disorder, hallucinations and depression, symptoms which are frequently as troublesome as the motor symptoms of PD. All these symptoms are present in narcolepsy, which is linked to a selective loss of hypocretin (Hcrt) neurons. In this study, the Hcrt system was examined to determine if Hcrt cells are damaged in PD. The hypothalamus of 11 PD (mean age 79 +/- 4) and 5 normal (mean age 77 +/- 3) brains was examined. Sections were immunostained for Hcrt-1, melanin concentrating hormone (MCH) and alpha synuclein and glial fibrillary acidic protein (GFAP). The substantia nigra of 10 PD brains and 7 normal brains were used for a study of neuromelanin pigmented cell loss. The severity of PD was assessed using the Hoehn and Yahr scale and the level of neuropathology was assessed using the Braak staging criteria. Cell number, distribution and size were determined with stereologic techniques on a one in eight series. We found an increasing loss of hypocretin cells with disease progression. Similarly, there was an increased loss of MCH cells with disease severity. Hcrt and MCH cells were lost throughout the anterior to posterior extent of their hypothalamic distributions. The percentage loss of Hcrt cells was minimal in stage I (23%) and was maximal in stage V (62%). Similarly, the percentage loss of MCH cells was lowest in stage I (12%) and was highest in stage V (74%). There was a significant increase (P = 0.0006, t = 4.25, df = 15) in the size of neuromelanin containing cells in PD patients, but no difference in the size of surviving Hcrt (P = 0.18, t = 1.39, df = 14) and MCH (P = 0.28, t = 1.39, df = 14) cells relative to controls. In summary, we found that PD is characterized by a massive loss of Hcrt neurons. Thus, the loss of Hcrt cells may be a cause of the narcolepsy-like symptoms of PD and may be ameliorated by treatments aimed at reversing the Hcrt deficit. We also saw a substantial loss of hypothalamic MCH neurons. The losses of Hcrt and MCH neurons are significantly correlated with the clinical stage of PD, not disease duration, whereas the loss of neuromelanin cells is significantly correlated only with disease duration. The significant correlations that we found between the loss of Hcrt and MCH neurons and the clinical stage of PD, in contrast to the lack of a relationship of similar strength between loss of neuromelanin containing cells and the clinical symptoms of PD, suggests a previously unappreciated relationship between hypothalamic dysfunction and the time course of the overall clinical picture of PD.
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PMID:Hypocretin (orexin) cell loss in Parkinson's disease. 1789 5

(1) Narcolepsy is characterised by sudden, overwhelming daytime drowsiness, sometimes associated with cataplexy (more or less complete loss of muscle tone during an emotional reaction). (2) Modafinil moderately reduces daytime drowsiness but has no effect on cataplexy. Methylphenidate, an amphetamine psychostimulant, seems to act on both drowsiness and cataplexy, although its clinical evaluation is limited to observational series. (3) Oxybic acid, long used in general anaesthesia, but also misused for recreational and criminal purposes (chemical or drug-induced submission), has been approved to treat adults with both narcolepsy and cataplexy, in the form of an oral solution of sodium oxybate. (4) The rationale behind the use of sodium oxybate is to re-establish a near-normal pattern of the different phases of sleep. Because of its short-lasting action, sodium oxybate has to be taken once at bedtime and then again 2.5 to 4 hours later. (5) Clinical evaluation mainly consists of 4 double-blind placebo-controlled trials of sodium oxybate. Three short-term trials, involving 136 patients treated for 4 weeks and 228 and 270 patients treated for 8 weeks, showed that sodium oxybate at a dose of 4.5 g to 9 g a day reduced the number of cataplexy attacks but that a dose of at least 6 g was needed to reduce daytime drowsiness. A trial involving 56 patients who had been taking sodium oxybate for nearly 2 years, assessed the effects of stopping versus continuing treatment. The results suggest that sodium oxybate is effective in the long term. (6) During clinical trials, 61% of patients had adverse effects attributed to sodium oxybate. These included gastrointestinal disorders (nausea (18%)), neurological disorders (dizziness (15%), headache (6%)), confusion (3%), and enuresis (7%). (7) Altered consciousness and respiratory depression occurred after a single intake of a dose two or three times higher than the recommended dose. (8) Misuse, especially to obtain chemical or drug-induced submission (i.e. as a 'date rape' drug), is facilitated by the odourless and colourless nature of the oral solution. (9) In practice, for some patients who are seriously affected by persistent episodes of cataplexy or drowsiness, despite treatment of narcolepsy, sodium oxybate is preferable to methylphenidate, which has been less thoroughly evaluated. However, the risks of misuse and overdose mean that this drug should only be proposed to patients in whom the benefits are likely to outweigh the risks.
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PMID:Sodium oxybate: new drug. Fewer attacks of cataplexy in some patients. 1758 23

Hypocretin (Hcrt, also known as orexin) is a hypothalamic neuropeptide linked to narcolepsy, a disorder diagnosed by the appearance of rapid eye-movement sleep (REMS)-state characteristics during waking. Major targets of Hcrt-containing fibers include the locus coeruleus and the raphe nucleus, areas with important roles in regulation of mood and sleep. A relationship between REMS and mood is suggested by studies demonstrating that REMS-deprivation (REMSD) ameliorates depressive symptoms in humans. Additional support is found in animal studies where antidepressants and REMSD have similar effects on monoamiergic systems thought to be involved in major depression. Recently, we have reported that Wistar-Kyoto (WKY) rats, an animal model of depression, have reduced number and size of hypothalamic cells expressing Hcrt-immunoractivity compared to the parent, Wistar (WIS) strain, suggesting the possibility that the depressive-like attributes of the WKY rat may be determined by this relative reduction in Hcrt cells [Allard, J.S., Tizabi, Y., Shaffery, J.P., Trouth, C.O., Manaye, K., 2004. Stereological analysis of the hypothalamic hypocretin/orexin neurons in an animal model of depression. Neuropeptides 38, 311-315]. In this study, we sought to test the hypothesis that REMSD would result in a greater increase in the number and/or size of hypothalamic, Hcrt-immunoreactive (Hcrt-ir) neurons in WKY, compared to WIS rats. The effect of REMSD, using the multiple-small-platforms-over-water (SPRD) method, on size and number of Hcrt-ir cells were compared within and across strains of rats that experienced multiple-large-platforms-over-water (LPC) as well as to those in a normal, home-cage-control (CC) setting. In accord with previous findings, the number of Hcrt-ir cells was larger in all three WIS groups compared to the respective WKY groups. REMSD produced a 20% increase (p<0.02) in the number of hypothalamic Hcrt-ir neurons in WKY rats compared to cage control WKY (WKY-CC) animals. However, an unexpected higher increase in number of Hcrt-ir cells was also observed in the WKY-LPC group compared to both WKY-CC (31%, p<0.001) and WKY-SPRD (20%, p<0.002) rats. A similar, smaller, but non-significant, pattern of change was noted in WIS-LPC group. Overall the data indicate a differential response to environmental manipulations where WKY rats appear to be more reactive than WIS rats. Moreover, the findings do not support direct antidepressant-like activity for REMSD on hypothalamic Hcrt neurons in WKY rats.
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PMID:Effects of rapid eye movement sleep deprivation on hypocretin neurons in the hypothalamus of a rat model of depression. 1759 Apr 34


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