{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T03:11:17Z","timestamp":1791515477931,"version":"4.3.4"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T00:00:00Z","timestamp":1599696000000},"content-version":"vor","delay-in-days":253,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Strategic Research Program for Brain Sciences from AMED","award":["JP19dm0107129"],"award-info":[{"award-number":["JP19dm0107129"]}]},{"name":"Strategic Research Program for Brain Sciences from AMED","award":["JP19dm0107083"],"award-info":[{"award-number":["JP19dm0107083"]}]},{"name":"JSPS KAKENHI","award":["JP18K07578"],"award-info":[{"award-number":["JP18K07578"]}]},{"name":"Scientific Research on Innovative Areas","award":["JP18H05435"],"award-info":[{"award-number":["JP18H05435"]}]},{"DOI":"10.13039\/501100008667","name":"SENSHIN Medical Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008667","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Autism spectrum disorder is a neurodevelopmental disorder characterized by difficulties in social communication and interaction, as well as repetitive and characteristic patterns of behaviour. Although the pathogenesis of autism spectrum disorder is unknown, being overweight or obesity during infancy and low weight at birth are known as risks, suggesting a metabolic aspect. In this study, we investigated adipose tissue development as a pathophysiological factor of autism spectrum disorder by examining the serum levels of adipokines and other metabolic markers in autism spectrum disorder children (n\u2009=\u2009123) and typically developing children (n\u2009=\u200992) at 4\u201312\u2009years of age. Among multiple measures exhibiting age-dependent trajectories, the leptin levels displayed different trajectory patterns between autism spectrum disorder and typically developing children, supporting an adipose tissue-dependent mechanism of autism spectrum disorder. Of particular interest, the levels of fatty acid binding protein 4 (FABP4) were significantly lower in autism spectrum disorder children than in typically developing subjects, at preschool age (4\u20136\u2009years old: n\u2009=\u200921 for autism spectrum disorder and n\u2009=\u200926 for typically developing). The receiver operating characteristic curve analysis discriminated autism spectrum disorder children from typically developing children with a sensitivity of 94.4% and a specificity of 75.0%. We re-sequenced the exons of the FABP4 gene in a Japanese cohort comprising 659 autism spectrum disorder and 1000 control samples, and identified two rare functional variants in the autism spectrum disorder group. The Trp98Stop, one of the two variants, was transmitted to the proband from his mother with a history of depression. The disruption of the Fabp4 gene in mice evoked autism spectrum disorder-like behavioural phenotypes and increased spine density on apical dendrites of pyramidal neurons, which has been observed in the postmortem brains of autism spectrum disorder subjects. The Fabp4 knockout mice had an altered fatty acid composition in the cortex. Collectively, these results suggest that an \u2018adipo-brain axis\u2019 may underlie the pathophysiology of autism spectrum disorder, with FABP4 as a potential molecule for use as a biomarker.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaa145","type":"journal-article","created":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T15:56:08Z","timestamp":1599753368000},"source":"Crossref","is-referenced-by-count":26,"title":["A potential role of fatty acid binding protein 4 in the pathophysiology of autism spectrum disorder"],"prefix":"10.1093","volume":"2","author":[{"given":"Motoko","family":"Maekawa","sequence":"first","affiliation":[{"name":"Laboratory for Molecular Psychiatry, RIKEN Center for Brain Science, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuo","family":"Ohnishi","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Psychiatry, RIKEN Center for Brain Science, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manabu","family":"Toyoshima","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Psychiatry, RIKEN Center for Brain Science, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chie","family":"Shimamoto-Mitsuyama","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Psychiatry, RIKEN Center for Brain Science, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Hamazaki","sequence":"additional","affiliation":[{"name":"Department of Public Health, Faculty of Medicine, University of Toyama, Toyama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1098-1290","authenticated-orcid":false,"given":"Shabeesh","family":"Balan","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Psychiatry, RIKEN Center for Brain Science, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuina","family":"Wada","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Psychiatry, RIKEN Center for Brain Science, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayoko","family":"Esaki","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Psychiatry, RIKEN Center for Brain Science, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Takagai","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry, Hamamatsu University School of Medicine, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji J","family":"Tsuchiya","sequence":"additional","affiliation":[{"name":"Research Center for Child Mental Development, Hamamatsu University School of Medicine, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiko","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Hirosaki University School of Medicine, Aomori, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhide","family":"Iwata","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurology, Fukude Nishi Hospital, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Nara","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, Miyagi Children's Hospital, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshimi","family":"Iwayama","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Psychiatry, RIKEN Center for Brain Science, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Toyota","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Psychiatry, RIKEN Center for Brain Science, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yayoi","family":"Nozaki","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Psychiatry, RIKEN Center for Brain Science, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisako","family":"Ohba","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Psychiatry, RIKEN Center for Brain Science, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Psychiatry, RIKEN Center for Brain Science, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuko","family":"Hisano","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Psychiatry, RIKEN Center for Brain Science, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeru","family":"Matsuoka","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Faculty of Medicine, Oita University, Oita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatsugu","family":"Tsujii","sequence":"additional","affiliation":[{"name":"School of Contemporary Sociology, Chukyo University, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norio","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurology, Fukude Nishi Hospital, Shizuoka, 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