CSF hypocretin‐1 (orexin‐A) concentrations in narcolepsy with and without cataplexy and idiopathic hypersomnia

Kanbayashi, Takashi; Inoue, Yuichi; Chiba, Shigeru; Aizawa, Rika; Saitō, Yasushi; Tsukamoto, Haruko; Fujii, Yutaka; Nishino, Seiji; Shimizu, Tetsuo

doi:10.1046/j.1365-2869.2002.00284.x

Cited by 187 publications

(104 citation statements)

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“…12 It has been reported that SNP rs1154155 located in TCRA locus was associated with hypocretin deficient narcolepsy with cataplexy. 4 Meanwhile, the CSF hypocretin-1 levels of most of the narcoleptics without cataplexy are within the normal range except for some cases, 6,13 indicating that many of the EHS patients might not be hypocretin deficient and SNP rs1154155 might also be associated with hypocretin non-deficient hypersomnias. However, the CSF hypocretin-1 measurements were not performed in this study.…”

Section: Discussionmentioning

confidence: 99%

Polymorphism located in TCRA locus confers susceptibility to essential hypersomnia with HLA-DRB11501-DQB10602 haplotype

et al. 2009

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Essential hypersomnia (EHS) exhibits excessive daytime sleepiness without cataplexy and is associated with the HLA-DRB1*1501-DQB1*0602 haplotype, similar to narcolepsy with cataplexy. Single-nucleotide polymorphism (SNP) rs1154155 located in the T-cell receptor a (TCRA) locus has been recently identified as a novel genetic marker of susceptibility for narcolepsy with cataplexy. We investigated whether the SNP was associated with EHS in the Japanese population. We found a significant association with EHS patients possessing the HLA-DRB1*1501-DQB1*0602 haplotype, compared with HLA-matched healthy individuals (P allele ¼0.008; P positivity ¼5Â10 À4 ), whereas no significant association was observed for EHS patients without this haplotype. Thus, TCRA is a plausible candidate for susceptibility to EHS patients positive for the HLA-DRB1*1501-DQB1*0602 haplotype.

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Section: Discussionmentioning

confidence: 99%

Polymorphism located in TCRA locus confers susceptibility to essential hypersomnia with HLA-DRB11501-DQB10602 haplotype

et al. 2009

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“…In contrast, nearly all individuals with N-C have normal CSF concentrations of hypocretin. 1,11,12 Considering the role of hypocretin in reward-seeking behavior and addiction, we hypothesized that individuals with N+C (low or absent CSF hypocretin) would show less risk-taking behavior than individuals with N-C (normal hypocretin levels).…”

Section: Part I: Questionnairesmentioning

confidence: 99%

“…In contrast, nearly all individuals with N-C have normal CSF concentrations of hypocretin. 1,11,12 We excluded subjects with a prior history of addiction, substance abuse, or psychiatric illness. This may seem counterintuitive, as these exclusion criteria are directly related to our main hypothesis.…”

Section: Limitationsmentioning

confidence: 99%

Reward-Seeking Behavior in Human Narcolepsy

Dimitrova

Fronczek

Ploeg

et al. 2011

Journal of Clinical Sleep Medicine

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Study Objectives: The hypocretin system enhances signaling in the mesolimbic pathways regulating reward processing and addiction. Because individuals with narcolepsy with cataplexy have low hypocretin levels, we hypothesized that they may be less prone to risk-and reward-seeking behaviors, including substance abuse. Design: Endpoints were performance on an array of psychometric tests (including the Eysenck Impulsiveness Scale, the Zuckerman Sensation Seeking Scale, the Gormally Binge Eating Scale, and the Beck Depression and Anxiety Inventory) and on the Balloon Analogue Risk Task (BART). Setting: Tertiary narcolepsy referral centers in Leiden (The Netherlands) and Boston (USA). Patients: Subjects with narcolepsy with cataplexy (n = 30), narcolepsy without cataplexy (n = 15), and controls (n = 32) matched for age, sex, and smoking behavior. Interventions: None. Measurements and Results: There was no difference in risktaking behavior between narcolepsy with or without cataplexy and the control group, as measured using the BART and the array of questionnaires. However, subjects in the narcolepsy with cataplexy group had significantly higher scores on the Eysenck Impulsiveness Scale (p < 0.05), with 10.0% categorized as impulsive, compared to 6.7% of the narcolepsy without cataplexy group and none of the controls. Narcoleptics with cataplexy also scored significantly higher than controls on the Binge Eating Scale (p < 0.05), with moderate or severe binge eating in 23%. On the depression and anxiety scales, all narcolepsy patients, especially those with cataplexy, scored significantly higher than controls. Conclusions:We found that narcoleptics with or without cataplexy generally have normal risk-taking behavior, but narcoleptics with cataplexy were more impulsive and more prone to binge eating than patients without cataplexy and controls. Our findings shed new light on the relation between sleepiness and impulsiveness. Furthermore, rates of depression and anxiety were higher in all narcoleptic subjects. However, using the current methods, no evidence could be found to support the hypothesis that hypocretin deficiency would affect reward-processing in humans. Keywords: Narcolepsy, cataplexy, hypocretin, orexin, risktaking, addiction, reward-seeking, substance abuse, sleep, sleepiness Citation: Dimitrova A; Fronczek R; Van der Ploeg J; Scammell T; Gautam S; Pascual-Leone A; Lammers GJ. Rewardseeking behavior in human narcolepsy. S C I E N T I F I C I N V E S T I G A T I O N SN arcolepsy with cataplexy is caused by an extensive loss of the neurons producing the hypocretin (orexin) neuropeptides. 1,2 Loss of these essential signaling molecules results in chronic daytime sleepiness, cataplexy, and other REM sleep associated phenomena. 3 In addition, considerable research indicates that the hypocretin system enhances signaling in the mesolimbic pathways that regulate reward processing and addiction, and hypocretin is now considered a key factor in of the neural mechanisms of drug addiction. 4,5 In response to drugs of a...

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“…These neurons are located in the ventral lateral hypothalamic nucleus in dogs and have extensive connections throughout the central nervous system (CNS) that promote wakefulness and muscle tone in response to the release of hypocretin 6. Humans with primary narcolepsy who suffer from cataplexy as part of their disease are classified as type 1, and the majority have low or undetectable levels of hypocretin in the CSF 7, 8, 9. In type 2 primary narcolepsy, cataplexy is not a component, and CSF hypocretin levels are normal.…”

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confidence: 99%

Pituitary Macrotumor Causing Narcolepsy‐Cataplexy in a Dachshund

Schmid

Hodshon

Olin

et al. 2017

Veterinary Internal Medicne

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Familial narcolepsy secondary to breed‐specific mutations in the hypocretin receptor 2 gene and sporadic narcolepsy associated with hypocretin ligand deficiencies occur in dogs. In this report, a pituitary mass is described as a unique cause of narcolepsy‐cataplexy in a dog. A 6‐year‐old male neutered Dachshund had presented for acute onset of feeding‐induced cataplexy and was found to have a pituitary macrotumor on magnetic resonance imaging (MRI). Cerebral spinal fluid hypocretin‐1 levels were normal, indicating that tumor effect on the ventral lateral nucleus of the hypothalamus was not the cause of the dog's narcolepsy‐cataplexy. The dog was also negative for the hypocretin receptor 2 gene mutation associated with narcolepsy in Dachshunds, ruling out familial narcolepsy. The Dachshund underwent stereotactic radiotherapy (SRT), which resulted in reduction in the mass and coincident resolution of the cataplectic attacks. Nine months after SRT, the dog developed clinical hyperadrenocorticism, which was successfully managed with trilostane. These findings suggest that disruptions in downstream signaling of hypocretin secondary to an intracranial mass effect might result in narcolepsy‐cataplexy in dogs and that brain MRI should be strongly considered in sporadic cases of narcolepsy‐cataplexy.

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CSF hypocretin‐1 (orexin‐A) concentrations in narcolepsy with and without cataplexy and idiopathic hypersomnia

Cited by 187 publications

References 5 publications

Polymorphism located in TCRA locus confers susceptibility to essential hypersomnia with HLA-DRB11501-DQB10602 haplotype

Polymorphism located in TCRA locus confers susceptibility to essential hypersomnia with HLA-DRB11501-DQB10602 haplotype

Reward-Seeking Behavior in Human Narcolepsy

Pituitary Macrotumor Causing Narcolepsy‐Cataplexy in a Dachshund

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CSF hypocretin‐1 (orexin‐A) concentrations in narcolepsy with and without cataplexy and idiopathic hypersomnia

Cited by 187 publications

References 5 publications

Polymorphism located in TCRA locus confers susceptibility to essential hypersomnia with HLA-DRB1*1501-DQB1*0602 haplotype

Polymorphism located in TCRA locus confers susceptibility to essential hypersomnia with HLA-DRB1*1501-DQB1*0602 haplotype

Reward-Seeking Behavior in Human Narcolepsy

Pituitary Macrotumor Causing Narcolepsy‐Cataplexy in a Dachshund

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Polymorphism located in TCRA locus confers susceptibility to essential hypersomnia with HLA-DRB11501-DQB10602 haplotype

Polymorphism located in TCRA locus confers susceptibility to essential hypersomnia with HLA-DRB11501-DQB10602 haplotype