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Query: UMLS:C0917801 (insomnia)
 10,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the effects of odorant inhalation on the sleep-wake states in rats. Odorants used in the experiment were clove, jasmine, lavender, lemon, peppermint, pine, rose, sandalwood, valerian, and ylang-ylang. Valerian and rose inhalation significantly prolonged the pentobarbital-induced sleeping time, whereas lemon inhalation significantly shortened it. The effect of valerian inhalation was markedly noticeable. In the anosmic rats, a significant effect of odorants on the pentobarbital sleep time was not seen. Electroencephalographic studies on natural sleep revealed that rose inhalation did not exert any significant effect on sleep, but a significant shortening in sleep latency and a significant prolonging in total sleep time were observed with valerian inhalation, whereas a significant prolonging in sleep latency was observed with lemon inhalation. Such effects of valerian and lemon inhalation were not admitted in anosmic rats. gamma-Aminobutyric acid (GABA) transaminase assay indicates that valerian inhalation decreases the activity of the enzyme and enhances GABA activity. Although valerian has been reported to exert a good effect for sleep as a medicine for internal use, the present study is the first medical report suggesting that the inhalation of valerian may enhance the sleep. On the other hand, the present results may suggest the possibility that lemon inhalation may cause a worsening of insomnia symptoms.
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PMID:The sleep-enhancing effect of valerian inhalation and sleep-shortening effect of lemon inhalation. 1685 58

This review examines the relationship between sleep and depression. Most depressive disorders are characterized by subjective sleep disturbances, and the regulation of sleep is intricately linked to the same mechanisms that are implicated in the pathophysiology of depression. After briefly reviewing the physiology and topography of normal sleep, the disturbances revealed in studies of sleep in depression using polysomnographic recordings and neuroimaging assessments are discussed. Next, treatment implications of the disturbances are reviewed at both clinical and neurobiologic levels. Most antidepressant medications suppress rapid eye movement (REM) sleep, although this effect is neither necessary nor sufficient for clinical efficacy. Effects on patients' difficulties initiating and maintaining sleep are more specific to particular types of antidepressants. Ideally, an effective antidepressant will result in normalization of disturbed sleep in concert with resolution of the depressive syndrome, although few interventions actually restore decreased slow-wave sleep. Antidepressants that block central histamine 1 and serotonin 2 tend to have stronger effects on sleep maintenance, but are also prone to elicit complaints of daytime sedation. Adjunctive treatment with sedative hypnotic medications--primarily potent, shorter-acting benzodiazepine and gamma-aminobutyric acid (GABA A)-selective compounds such as zolpidem--are often used to treat associated insomnia more rapidly. Cognitive behavioral therapy and other nonpharmacologic strategies are also helpful.
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PMID:Depression and sleep: pathophysiology and treatment. 1688 7

Patients with neurologic disorders commonly experience sleep dysfunction and psychiatric disorders. The most common sleep dysfunction is insomnia, which is a primary symptom in 30% to 90% of psychiatric disorders. Insomnia and fatigue are prominent symptoms of anxiety disorders and major depression, including patients who are treated but have residual symptoms. Anxiety and depressive disorders account for 40% to 50% of all cases of chronic insomnia. It is also recognized that primary insomnia and other primary sleep disorders produce symptoms that are similar to those reported by patients with psychiatric disorders. A clinician must judge whether sleep deprivation causes mood disturbance or whether depressive or anxiety disorder represents the primary reason for sleep dysfunction. When insomnia is comorbid with mild to moderate depression, therapy should begin with bedtime dosing of sedating antidepressants such as mirtazapine, nefazodone, or tricyclic antidepressants, which are preferred because of their sedative effects, although side effects may limit their usefulness. Intervention for chronic insomnia is similar in nonpsychiatric and psychiatric patients. Behavioral therapies, particularly cognitive behavioral therapy, and lifestyle changes show significant long-term efficacy as treatments for chronic insomnia. Sedative hypnotic agents are the most studied agents to treat insomnia, particularly those that are active through the benzodiazepine receptor-GABA complex, such as benzodiazepines, eszopiclone, zaleplon, and zolpidem. The new melatonin-receptor agonist ramelteon has not yet been studied in psychiatric patients. Prescription of adjunctive trazodone 50 to 150 mg is a common clinical practice to treat comorbid insomnia during antidepressant therapy, but published data are surprisingly limited when considered against the frequent usage of trazodone. Although there has been insufficient research on the use of atypical antipsychotic agents in severe insomnia, psychiatrists use quetiapine, olanzapine, or other agents to lessen agitation that disrupts sleep onset or maintenance. When insomnia or hypersomnia continues even as mood, anxiety, or thought disorders improve with standard therapy, the physician should consider the potential presence of underlying sleep disorders.
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PMID:Treatment of sleep dysfunction and psychiatric disorders. 1690 76

The sleep-wake cycle is under the control of the circadian clock. Recent advances in rhythm biology have identified molecular clocks and their key regulating genes. Circadian clock genes (Clock, Per) were first isolated in Drosophila, and their homologous counterparts have been found in mammals. Some of the circadian master genes have been shown to influence sleeping behavior. For instance, a point mutation in a human clock gene (Per2) was shown to produce the rare advanced sleep phase syndrome, whereas a functional polymorphism in Per3 is associated with the more frequent delayed sleep phase syndrome. Furthermore, a study examining the association between Clock gene polymorphisms and insomnia revealed a higher recurrence of initial, middle, and terminal insomnia in patients homozygous for the Clock genotype. Other genes have been shown to contribute to sleep pathologies. A point mutation in the prion protein gene appears to be the cause of fatal familial insomnia. A missense mutation has been found in the gene encoding the GABA-A beta 3 subunit in a patient with chronic insomnia. In both animal models and humans, a deficiency in the hypocretin/orexin system was proposed to be responsible for narcolepsy. Selective destruction of hypocretin neurons is the most probable culprit in humans. These findings suggest that the genetic contribution to sleep disorders and wake determinants is more important than originally thought. Beyond sleep, light/dark cycles and sleep deprivation appear also to be associated with eating habits, and epidemics of obesity have to be evaluated in the context of shortened sleep duration.
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PMID:Genetics of the sleep-wake cycle and its disorders. 1697 29

Central nervous system function is critically dependent upon an exquisitely tuned balance between excitatory synaptic transmission, mediated primarily by glutamate, and inhibitory synaptic transmission, mediated primarily by GABA. Modulation of either excitation or inhibition would be expected to result in altered functionality of finely tuned synaptic pathways and global neural systems, leading to altered nervous system function. Administration of positive or negative modulators of ligand-gated ion channels has been used extensively and successfully in CNS therapeutics, particularly for the induction of sedation and treatment of anxiety, seizures, insomnia, and pain. Excessive activation of excitatory glutamate receptors, such as in cerebral ischemia, can result in neuronal damage via excitotoxic mechanisms. The discovery that neuroactive steroids exert rapid, direct effects upon the function of both excitatory and inhibitory neurotransmitter receptors has raised the possibility that endogenous neurosteroids may play a regulatory role in synaptic transmission by modulating the balance between excitatory and inhibitory neurotransmission. The sites to which neuroactive steroids bind may also serve as targets for the discovery of therapeutic neuromodulators.
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PMID:Sulfated steroids as endogenous neuromodulators. 1702 38

After our initial discovery of under expression of the GABA(A) receptor delta subunit in a genome wide screening for differentially expressed mRNAs in brain of fragile X mice, a validated model for fragile X mental retardation syndrome, we analyzed expression of the 17 remaining subunits of the GABA(A) receptor using real-time PCR. We confirmed nearly 50% under expression of the delta subunit and found a significant 35%-50% reduction in expression of 7 additional subunit mRNAs, namely alpha(1), alpha(3), and alpha(4), beta(1) and beta(2) and gamma(1) and gamma(2), in fragile X mice compared to wild-type littermates. In concordance with previous results, under expression was found in cortex, but not in cerebellum. Moreover, decreased expression of specific GABA(A) receptor subunits in fragile X syndrome seems to be an evolutionary conserved hallmark since in the fragile X fly (Drosophila melanogaster) model we also found almost 50% under expression of all 3 subunits which make up the invertebrate GABA receptor, namely Grd, Rdl and Lcch3. In addition, we demonstrated a direct correlation between the amount of dFmrp and the expression of the GABA receptor subunits Rdl and Grd. Our results add evidence to previous observations of an altered GABAergic system in fragile X syndrome. Because GABA(A) receptors are the major inhibitory receptors in brain, involved in anxiety, depression, insomnia, learning and memory and epilepsy, processes also disturbed in fragile X patients, the well described GABA(A) receptor pharmacology might open new powerful opportunities for treatment of the behavioral and epileptic phenotype associated with fragile X syndrome.
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PMID:Decreased expression of the GABAA receptor in fragile X syndrome. 1704 29

gamma-Hydroxybutyrate (GHB) is an endogenous short chain fatty acid and a, mostly oral, pharmacological compound that has been utilised in a variety of ways. Endogenously, GHB is synthesised locally within the CNS, mostly from its parent compound GABA. Sodium oxybate is the sodium salt of GHB and is used for the exogenous oral administration of GHB. It is likely that supraphysiological concentrations of GHB from exogenous administration produce qualitatively different neuronal actions than those produced by endogenous GHB concentrations. Evidence suggests a role for GHB as a neuromodulator/neurotransmitter. Under endogenous conditions and concentrations, and depending on the cell group affected, GHB may increase or decrease neuronal activity by inhibiting the release of neurotransmitters that are co-localised with GHB. After exogenous administration, most of the observed behavioural effects appear to be mediated via the activity of GHB at GABA(B) receptors, as long as the concentration is sufficient to elicit binding, which does not happen at endogenous concentrations. Endogenous and exogenous GHB is rapidly and completely converted into CO(2) and H(2)O through the tricarboxylic acid cycle (Krebs cycle). Sodium oxybate has been observed to modulate sleep in nonclinical study participants, and sleep and wakefulness in clinical populations, including groups with insomnia, fibromyalgia and narcolepsy. In narcolepsy, sodium oxybate has shown dose-related effects on various properties of sleep, including increases in slow-wave sleep duration and delta power, and a reduced number of night-time awakenings. Furthermore, multiple measures of daytime sleepiness and cataplexy demonstrated consistent short- and long-term improvement in response to night-time sodium oxybate therapy. The most common reported adverse events include dose-related headache, nausea, dizziness and somnolence.
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PMID:gamma-Hydroxybutyrate/sodium oxybate: neurobiology, and impact on sleep and wakefulness. 1714 Feb 79

Insomnia and hypersomnia are frequent sleep disorders, and they are most often treated pharmacologically with hypnotics and wake-promoting compounds. These compounds act on classical neurotransmitter systems, such as benzodiazepines on GABA-A receptors, and amfetamine-like stimulants on monoaminergic terminals to modulate neurotransmission. In addition, acetylcholine, amino acids, lipids and proteins (cytokines) and peptides, are known to significantly modulate sleep and are, therefore, possibly involved in the pathophysiology of some sleep disorders. Due to the recent developments of molecular biological techniques, many neuropeptides have been newly identified, and some are found to significantly modulate sleep. It was also discovered that the impairment of the hypocretin/orexin neurotransmission (a recently isolated hypothalamic neuropeptide system) is the major pathophysiology of narcolepsy, and hypocretin replacement therapy is anticipated to treat the disease in humans. In this article, the authors briefly review the history of neuropeptide research, followed by the sleep modulatory effects of various neuropeptides. Finally, general strategies for the pharmacological therapeutics targeting the peptidergic systems for sleep disorders are discussed.
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PMID:Neuropeptides as possible targets in sleep disorders. 1715 33

RLS cases may carry a genetic vulnerability called EEG alpha activity gate dyscontrols which appear during changes in vigilance and generally during sleep. It is triggered by forced EEG shifts either from alpha activity to delta or high alpha. Expressions of alpha activity gate dyscontrols may have a gate effect that trigger a second vulnerability-dopamine receptor specific individual sensitivity (DRSIS) and this leads to a deficiency in dopamine transmissions at diencephalospinal dopamine system (DSDS). Due to altered gene expressions in states of dopamine receptor function, DRSIS EEGs and RLS symptoms may be interpreted as follows: A. Disinhibition state is alpha activity gate dyscontrols induced inhibition of DSDS inhibitory dopamine modulations. Dopaminergic disinhibitions inhibit inhibitory interneurons of sensory and motor nuclei neurons that are involved in RLS. These sleep sensitive inhibitory interneurons possibly have GABA-ergic functions in sleep. (I) DSDS thalamic neurons' disinhibitory effects in thalamus on GABA-ergic interneurons of: (a) Intralaminar nuclei non-discriminative sensation neurons at thalamocortical premotor network leading to symptom of "a sense of urgency to move" generally referenced to legs.(b) Reticular thalamic nucleus (RTN) neurons. At polysomnography,during NREM sleep, disinhibited RTN neurons show alpha activity gate dyscontrol 1. These are recurrent subtypes of CAP in alpha band (7-12 Hz) pointing a difficulty in shifting to subtypes of CAP in low delta bands (0.25-2.5 Hz) and sleep fragmentations.(II) Supraspinal disinhibitory projections from DSDS thalamic neurons on GABA-ergic interneurons of: (a) Sensory neurons at posterior horns of spinal cord leading to dysesthesias, generally referenced to legs.(b) Medullary-reticulospinal neurons and by way of independent spinal rhythm generators on motoneurons leading to periodic limb movements in sleep.B. Activation state is an increase in symptoms. Sensory intralaminar and motor pontin nuclei neurons are in fact excitatory but are disinhibited in RLS. Due to altered gene expression, these neurons begin to perceive 'disinhibition' as reduced inhibition. Their glutamate receptors may activate deficient dopamine transmissions on RTN leading to alpha activity gate dyscontrol 2. This implies a failure in preventing shifts to frequent subtypes of CAP in high alpha and low beta bands (12-13 Hz) resulting in an increase of sensorimotor symptoms and appearance of motor restlessness, behavioral arousals and insomnia. C. Inhibition state is spontaneous relief from sensorimotor symptoms. Short or long-term synaptic plasticities of dopamine receptors towards activations initiate negative feedbacks from inhibitory interneurons. They are supported by inhibitory dopamine modulations- alertness and some awareness generally with regular high alpha EEGs, supraspinal inhibitions and a reverse movement pattern of PLMS during standing up and continuing to walk.
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PMID:In restless legs syndrome, during changes in vigilance, the forced EEG shifts from alpha activity to delta or high alpha may lead to the altered states of dopamine receptor function and the symptoms. 1732 Mar 7

In the serum and cerebrospinal fluid of a patient with recurrent acute episodes of respiratory crises, autonomic symptoms and total insomnia (agrypnia), we identified a novel anti-neural complement fixing antibody directed against GABA(B) receptor (GABA(B)R). Patient purified IgG recognized a band of approximately 110 kDa on protein extracts of mouse cerebellum, cortex and brainstem and immunolabelled cultured Chinese hamster ovary (CHO) cells, transfected with human GABA(B)R1 and rat GABA(B)R2 receptors. Western blot analysis of transfected CHO homogenates showed the same band using both patient purified IgG and anti-GABA(B)R1 antibody. In order to verify the pathogenic role of these purified antibodies, we injected patient IgG intrathecally into cisterna magna of C57BL/6 mice pre-implanted with EEG electrodes and we observed severe ataxia followed by breathing depression and total suppression of slow wave sleep, as evidenced by EEG recording, in a dose-dependent manner. Immunohistochemistry on brain sections of mice injected with patient IgG showed the simultaneous presence of bound human IgG and C5b-9 deposits on Purkinje cells and cerebellar granular layer. After incubation with anti-GABA(B)R antibody, a marked reduction of receptor immunostaining was found with relative sparing of neuronal architecture. In conclusion we recognized an anti-neuronal autoantibody directed against GABA(B)R that is associated with autoimmune agrypnia and we showed that our patient purified IgG was able to induce in mice experimental autoimmune agrypnia characterized by a complex neurological syndrome affecting several CNS functions.
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PMID:A human anti-neuronal autoantibody against GABA B receptor induces experimental autoimmune agrypnia. 1733 94


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