Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The histaminergic tuberomamillary nucleus (TMN) controls arousal and attention, and the firing of TMN neurons is state-dependent, active during waking, silent during sleep. Thyrotropin-releasing hormone (TRH) promotes arousal and combats sleepiness associated with narcolepsy. Single-cell reverse-transcription-PCR demonstrated variable expression of the two known TRH receptors in the majority of TMN neurons. TRH increased the firing rate of most (ca 70%) TMN neurons. This excitation was abolished by the TRH receptor antagonist chlordiazepoxide (CDZ; 50 mum). In the presence of tetrodotoxin (TTX), TRH depolarized TMN neurons without obvious change of their input resistance. This effect reversed at the potential typical for nonselective cation channels. The potassium channel blockers barium and cesium did not influence the TRH-induced depolarization. TRH effects were antagonized by inhibitors of the Na(+)/Ca(2+) exchanger, KB-R7943 and benzamil. The frequency of GABAergic spontaneous IPSCs was either increased (TTX-insensitive) or decreased [TTX-sensitive spontaneous IPSCs (sIPSCs)] by TRH, indicating a heterogeneous modulation of GABAergic inputs by TRH. Facilitation but not depression of sIPSC frequency by TRH was missing in the presence of the kappa-opioid receptor antagonist nor-binaltorphimine. Montirelin (TRH analog, 1 mg/kg, i.p.) induced waking in wild-type mice but not in histidine decarboxylase knock-out mice lacking histamine. Inhibition of histamine synthesis by (S)-alpha-fluoromethylhistidine blocked the arousal effect of montirelin in wild-type mice. We conclude that direct receptor-mediated excitation of rodent TMN neurons by TRH demands activation of nonselective cation channels as well as electrogenic Na(+)/Ca(2+) exchange. Our findings indicate a key role of the brain histamine system in TRH-induced arousal.
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PMID:Excitation of histaminergic tuberomamillary neurons by thyrotropin-releasing hormone. 1935 73

The percentage of compliant continuous positive airway pressure (CPAP)-treated apnoeic patients that continue to experience residual excessive sleepiness (RES) is unknown. RES was defined by an Epworth Sleepiness Scale (ESS) score of >or=11. In total, 502 patients from 37 French sleep centres using CPAP >3 h night(-1) attending their 1-yr follow-up visit were eligible. ESS and polysomnographic data as well as symptoms, quality of life, depression scores and objective CPAP compliance at 1 yr were collected. Overall, 60 patients remained sleepy on CPAP (ESS 14.3+/-2.5) leading to a prevalence rate of RES of 12.0% (95% confidence interval (CI) 9.1-14.8). After having excluded associated restless leg syndrome, major depressive disorder and narcolepsy as confounding causes, the final prevalence rate of RES was 6.0% (95% CI 3.9-8.01). Patients with RES were younger and more sleepy at diagnosis. The relative risk of having RES was 5.3 (95% CI 1.6-22.1), when ESS before treatment was >or=11. Scores of emotional and energy Nottingham Health Profile domains were two times worse in patients with RES. As 230,000 obstructive sleep apnoea patients are currently treated in France by continuous positive airway pressure, more than 13,800 of them might suffer from residual excessive sleepiness.
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PMID:Prevalence of residual excessive sleepiness in CPAP-treated sleep apnoea patients: the French multicentre study. 1988 Jun 26

Changes regarding the immune system and specifically the cytokine system, of which tumor necrosis factor-alpha (TNF-alpha) is a part, have been shown to be involved in the development of neurological and psychiatric disorders such as multiple sclerosis, Parkinson's and Alzheimer's disease, depression, schizophrenia or narcolepsy. Besides, there is evidence that the risk of stroke correlates with the serum concentrations of different cytokines. Additionally, body weight, age and neuroendocrinological mechanism have a strong influence upon plasma levels of TNF-alpha and its soluble receptors (sTNF-Rs). TNF-alpha might contribute to the pathogenesis of these diseases by an activation of the hypothalamo-pituitary-adrenocortical (HPA) axis, an activation of neuronal serotonin transporters, the stimulation of the indoleamine 2,3-dioxygenase which leads to tryptophan depletion, by immunologically mediated destruction of neurons, or neurotoxic release of glutamate. Psychotropic drugs influence the TNF-alpha system, too. During psychopharmacological treatment of schizophrenia, some antipsychotics might act on neurotransmitter metabolism via inducing the proinflammatory cytokine system. Hopefully, these hypotheses may lead to new therapeutical strategies for psychiatric patients in the near future.
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PMID:[The relevance of the TNF-alpha system in psychiatric disorders]. 1941 85

Narcolepsy is a neurological disorder affecting the regulation of sleep and wakefulness. It is characterized by excessive daytime sleepiness, cataplexy, and other rapid eye movement (REM) sleep-associated manifestations (eg, hypnagogic hallucinations and sleep paralysis). The recognition of this disorder is usually delayed by 10 to 15 years, largely because of its protean manifestations, insidious nature, and lack of physician awareness. Delayed diagnosis is associated with poor quality of life, depression, and increased likelihood of accidents. Health care providers should include narcolepsy in the differential diagnosis of patients with excessive sleepiness, chronic fatigue, sleep-disordered breathing, depression, and attention-deficit/hyperactivity disorder. Narcolepsy is a lifelong disorder that often requires pharmacological treatments, which may include wake-promoting stimulants for excessive sleepiness and gamma-hydroxybutyrate (sodium oxybate) and antidepressants for REM sleep-associated manifestations. This article presents a case of a 47-year-old man with long-standing sleepiness and cataplexy who was eventually diagnosed with narcolepsy 30 years after the first onset of symptoms. The presenting manifestations of narcolepsy, diagnostic criteria, and its management are also discussed.
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PMID:Narcolepsy--master of disguise: evidence-based recommendations for management. 1949 46

This paper reviews studies that have examined associations between unusual sleep experiences (including nightmares, vivid dreaming, narcolepsy symptoms, and complex nighttime behaviors) and dissociation and schizotypy. Using correlational studies and structural analyses, evidence is provided that unusual sleep experiences, dissociation, and schizotypy belong to a common domain. It is demonstrated that unusual sleep experiences show specificity to dissociation and schizotypy compared to other daytime symptoms (e.g., anxiety, depression, substance use) and other sleep disturbances (e.g., insomnia, lassitude/fatigue). The paper also outlines the methodological limitations of the existing evidence and makes suggestions for future research. Finally, three models for the overlap of daytime and nighttime symptoms are reviewed, including biological abnormalities, trauma, and personality traits. Although further research is needed, it is suggested that daytime and nighttime symptoms result from problems with sleep-wake state boundaries, which may be precipitated by stress or trauma. In addition, association between daytime and nighttime symptoms can be attributed to the higher order personality trait of Oddity.
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PMID:Unusual sleep experiences, dissociation, and schizotypy: Evidence for a common domain. 1958 Oct 31

A voluminous literature describes the relationship between disturbed sleep and depression. The breakdown of sleep is one of the cardinal features of depression and often also heralds its onset. Frequent arousals, periods of wakefulness and a short sleep onset REM latency are typical polysomnographic features of depression. The short latency to REM sleep has been attributed to the combination of a monoaminergic deficiency and cholinergic supersensitivity and these irregularities have been proposed to form the biological basis of the disorder. A similar imbalance between monoaminergic and cholinergic neurotransmission has been found in narcolepsy, a condition in which frequent awakenings, periods of wakefulness and short sleep onset REM latencies are also characteristic findings during sleep. In many cases of narcolepsy, this imbalance appears to result from a deficiency of hypocretin but once established, whether in depression or narcolepsy, this disequilibrium sets the stage for the dissociation or premature appearance of REM sleep and for the dissociation of the motor inhibitory component of REM sleep or cataplexy. In the presence of this monoaminergic/cholinergic imbalance, gammahydroxybutyrate (GHB) may acutely further reduce the latency of REM sleep and induce cataplexy, in both patients with narcolepsy or depression. On the other hand, the repeated nocturnal application of GHB in patients with narcolepsy improves the continuity of sleep, prolongs the latency to REM sleep and prevents cataplexy. Evidence to date suggests that GHB may restore the normal balance between monoaminergic and cholinergic neurotransmission. As such, the repeated use of GHB at night and the stabilization of sleep over time makes GHB an effective treatment for narcolepsy and a potentially effective treatment for depression.
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PMID:Narcolepsy and depression and the neurobiology of gammahydroxybutyrate. 1965 34

It was discovered in 2000 that a deficit of hypocretin/orexin neurons is responsible for causing narcolepsy. Today, agonists for orexin receptors are being explored in order to establish an orexin replacement therapy, but the process is still at the stage of research. On the other hand, orexin antagonists are now undergoing clinical trials as a hypnotic. Activation of the dopamine system is effective against hypersomnia, and activation of the noradrenaline system is effective against cataplexy. Therefore, these two types of drugs have been used for treatment. Methylphenidate was mainly used, but recently modafinil has become mainstream. The action mechanism of methylphenidate is reuptake inhibition and release stimulation of dopamine. The action mechanism of modafinil is not fully explained, but is thought to be reuptake inhibition of dopamine. When methylphenidate was used for disorders other than narcolepsy, such as depression, dependence on the drug and abuse became an issue, and methylphenidate is no longer available for depression. It has been said that narcoleptic patients have a tendency to control the doses of methylphenidate at a low level of their own accord, and that they have a significantly low risk of developing a dependency on the drug. It has also been observed in mice with orexin deficit produced by molecular genetics that they have a significantly low development of dependency on amphetamine, a relative compound of methylphenidate. On the other hand, modafinil has been found to cause very little dependence, and is chosen as the principal drug in treatment. It was recently discovered that the histamine neurons, which are downstream of orexin neurons, are responsible for controlling arousal. It was also discovered that the CSF histamine was low in narcolepsy and other hypersomnia of central origin. Histamine H3 antagonists are being explored as a treatment for hypersomnia. H3 receptors are auto receptors located in the brain histamine neuron, and agonists act for suppression, antagonists for activation. They have shown good results in the animal experiments and phase 2 of clinical experiments.
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PMID:[Recent advance of treatments for narcolepsy and hypersomnia]. 1966 60

Modafinil is a novel wake-promoting agent approved for the treatment of excessive sleepiness associated with narcolepsy that holds significant promise as an alternative treatment to traditional psychostimulants for excessive fatigue associated with medical and psychiatric disorders and as augmentation medication for treatment-resistant depression.
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PMID:Modafinil: past, present and future. 1981 Sep 41

Although narcolepsy is a relatively uncommon condition, its impact on a child's life can be dramatic and disabling. Narcolepsy is characterized by excessive daytime sleepiness (EDS), with brief "sleep attacks" at very unusual times and usually associated with cataplexy (sudden loss of muscle control while awake, resulting in a fall, triggered by laughter). Other symptoms frequently reported are sleep paralysis (feeling of being unable to move or speak, even totally aware), hypnagogic hallucinations (vivid dreamlike experiences difficult to distinguish from reality) or disturbed night time sleep. Some children also experience depression or overweight-obesity. Although narcolepsy has been thoroughly studied, the exact cause is unknown. It appears to be a disorder of cerebral pathways that control sleep and wakefulness, involving dorsolateral hypothalamus and hypocretin. A genetic factor has been suggested, but narcolepsy in relatives is rare. Researchers have suggested that a set of genes combines with additional factors in a person's life to cause narcolepsy. The effective treatment of narcolepsy requires not only medication (usually stimulants, antidepressants and sodium oxybate), but also adjustments in life-style (scheduled naps). Management of this condition in children demands a comprehensive approach to the patient, that includes a correct diagnosis, pharmacological and non-pharmacological treatment and adjustments in the environment. These strategies can improve the child's self-esteem and ability to obtain a good education.
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PMID:[Narcolepsy with and without cataplexy: an uncommon disabling and unrecognized disease]. 1989 9

Tumor necrosis factor-alpha (TNF-alpha) is a glycoprotein hormone with important functions in inflammation and apoptosis. It plays a significant role as a pro-inflammatory cytokine in the defense against viral, bacterial and parasitic infections and autoimmune disorders. Furthermore, it influences energy homeostasis and has an anorexigenic effect on the hypothalamus. TNF-alpha has also been shown to be involved in the pathogenesis of psychiatric disorders such as depression or narcolepsy. Ghrelin is a peptide hormone which primarily regulates eating behavior through modulation of expression of orexigenic peptides in the hypothalamus. Ghrelin administration increases food intake and body weight, while weight loss in turn increases ghrelin levels. Secondly, it posesses anti-inflammatory properties. It also seems to have an impact on mental health as it is has been suggested to have antidepressant and anxiolytic properties. Therefore, TNF-alpha and ghrelin seem to have opposite effects regarding the hypothalamic regulation of eating behavior, modulation of the immune response and the state of mental health.
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PMID:TNF-alpha and ghrelin: opposite effects on immune system, metabolism and mental health. 2021 44


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