{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T08:17:14Z","timestamp":1768465034728,"version":"3.49.0"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2020,5,15]],"date-time":"2020-05-15T00:00:00Z","timestamp":1589500800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,11,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Narcolepsy type 1 (NT1) is a hypersomnia characterized by excessive daytime sleepiness and cataplexy. Inappropriate regulation of fatty acid metabolism has been suggested to be involved in the pathophysiology of NT1, but the detailed mechanisms remain uncertain. Here we performed a metabolomic analysis of cerebrospinal fluid samples from 14 NT1 and 17 control subjects using a novel capillary electrophoresis coupled with Fourier transform mass spectrometry. A total of 268 metabolites were identified and the amount of histidine was the most significantly increased in NT1 patients (p = 4.0 \u00d7 10\u20134). Validation analysis using high-performance liquid chromatography (HPLC) including independent replication samples also identified the association of histidine (p = 2.02 \u00d7 10\u20133). Further, levels of histamine, which is synthesized from histidine, were also examined using HPLC and were found to be significantly decreased in NT1 patients (p = 6.12 \u00d7 10\u20134). Pathway analysis with nominally significant metabolites identified several pathways related to the metabolism of glycogenic amino acids, suggesting that glycogenesis is enhanced in NT1 as a compensatory mechanism for fatty acid metabolism. We performed further exploratory analysis, searching for metabolites associated with sleep variables from polysomnography and the multiple sleep latency test. As a result, 5\u2032-deoxy-5\u2032-methylthioadenosine showed a significant association with apnea\u2013hypopnea index (p = 2.66 \u00d710\u20136). Moreover, gamma aminobutyric acid displayed a negative correlation with rapid eye movement sleep latency (REML), and thus might represent an intriguing target for future studies to elucidate how the controlling circuit of REM sleep is associated with abnormally short REML in NT1.<\/jats:p>","DOI":"10.1093\/sleep\/zsaa095","type":"journal-article","created":{"date-parts":[[2020,5,31]],"date-time":"2020-05-31T07:40:02Z","timestamp":1590910802000},"source":"Crossref","is-referenced-by-count":18,"title":["Metabolome analysis using cerebrospinal fluid from narcolepsy type 1 patients"],"prefix":"10.1093","volume":"43","author":[{"given":"Mihoko","family":"Shimada","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan"},{"name":"Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taku","family":"Miyagawa","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan"},{"name":"Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tohru","family":"Kodama","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiromi","family":"Toyoda","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katsushi","family":"Tokunaga","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan"},{"name":"Genome Medical Science Project (Toyama), National Center for Global Health and Medicine (NCGM), Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makoto","family":"Honda","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan"},{"name":"Seiwa Hospital, Institute of Neuropsychiatry, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,5,15]]},"reference":[{"key":"2020112501265062400_CIT0001","doi-asserted-by":"crossref","first-page":"S16","DOI":"10.1212\/WNL.50.2_Suppl_1.S16","article-title":"Genetic and familial aspects of 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All the patients were DR2 positive","volume":"24","author":"Juji","year":"1984","journal-title":"Tissue Antigens."},{"key":"2020112501265062400_CIT0010","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1086\/318799","article-title":"Complex HLA-DR and -DQ interactions confer risk of narcolepsy-cataplexy in three ethnic groups","volume":"68","author":"Mignot","year":"2001","journal-title":"Am J Hum Genet."},{"key":"2020112501265062400_CIT0011","doi-asserted-by":"crossref","first-page":"2566","DOI":"10.1002\/acn3.50908","article-title":"Children with narcolepsy type 1 have increased T-cell responses to orexins","volume":"6","author":"Cogswell","year":"2019","journal-title":"Ann Clin Transl Neurol."},{"key":"2020112501265062400_CIT0012","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.sleep.2019.08.017","article-title":"Flow cytometry T cell profiling in a recent-onset narcoleptic type 1 child: a case report","volume":"68","author":"Moresco","year":"2020","journal-title":"Sleep Med."},{"key":"2020112501265062400_CIT0013","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1038\/ng.372","article-title":"Narcolepsy is strongly associated with the T-cell receptor alpha locus","volume":"41","author":"Hallmayer","year":"2009","journal-title":"Nat Genet."},{"key":"2020112501265062400_CIT0014","doi-asserted-by":"crossref","first-page":"e1003270","DOI":"10.1371\/journal.pgen.1003270","article-title":"ImmunoChip study implicates antigen presentation to T cells in narcolepsy","volume":"9","author":"Faraco","year":"2013","journal-title":"PLoS Genet."},{"key":"2020112501265062400_CIT0015","doi-asserted-by":"crossref","first-page":"e1003880","DOI":"10.1371\/journal.pgen.1003880","article-title":"Genome wide analysis of narcolepsy in China implicates novel immune loci and reveals changes in association prior to versus after the 2009 H1N1 influenza pandemic","volume":"9","author":"Han","year":"2013","journal-title":"PLoS Genet."},{"key":"2020112501265062400_CIT0016","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/ng.734","article-title":"Common variants in P2RY11 are associated with narcolepsy","volume":"43","author":"Kornum","year":"2011","journal-title":"Nat Genet."},{"key":"2020112501265062400_CIT0017","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.bbi.2015.05.003","article-title":"A polymorphism in CCR1\/CCR3 is associated with narcolepsy","volume":"49","author":"Toyoda","year":"2015","journal-title":"Brain Behav Immun."},{"key":"2020112501265062400_CIT0018","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1038\/ng.231","article-title":"Variant between CPT1B and CHKB associated with susceptibility to narcolepsy","volume":"40","author":"Miyagawa","year":"2008","journal-title":"Nat Genet."},{"key":"2020112501265062400_CIT0019","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1432-1033.1997.00001.x","article-title":"The mitochondrial carnitine palmitoyltransferase system. 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