{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:02:56Z","timestamp":1791241376235,"version":"4.1.0"},"reference-count":85,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T00:00:00Z","timestamp":1748822400000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2021R1A2C1091893"],"award-info":[{"award-number":["2021R1A2C1091893"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012246","name":"Priority Academic Program Development of Jiangsu Higher Education Institutions","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31971319"],"award-info":[{"award-number":["31971319"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32171403"],"award-info":[{"award-number":["32171403"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003091","name":"Government of Shandong Province","doi-asserted-by":"publisher","award":["WST2021007"],"award-info":[{"award-number":["WST2021007"]}],"id":[{"id":"10.13039\/501100003091","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Autism spectrum disorder (ASD) is a neurodevelopmental condition that affects social communication and behaviors. While previous studies using animal models have substantially expanded our knowledge about ASD, the lack of an appropriate human model system that accurately recapitulates the human\u2010specific pathophysiology of ASD hinders the precise understanding of its etiology and the development of effective therapies. This study aims to replicate pathological phenotypes in cerebral organoids derived from idiopathic ASD patients and to conduct proof\u2010of\u2010concept research for the development of ASD therapeutics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted an in\u00a0vitro disease modeling study using cerebral organoids derived from three idiopathic ASD patients. Additionally, we performed organoid\u2010based phenotypic drug screening to identify potential therapeutic compounds that could ameliorate the phenotypes observed in cerebral organoids derived from idiopathic ASD patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Here we show that cerebral organoids derived from idiopathic ASD patients display malformation of the ventricular zones and impaired early neuronal differentiation. Through organoid\u2010based phenotypic drug screening, we successfully generated cerebral organoids with normal tissue architecture in which the delayed neuronal differentiation could also be accelerated. Notably, cerebral organoids from ASD patients exhibited a reduced number of GABAergic neurons compared to healthy controls, resulting in an imbalance in the excitatory and inhibitory neuron ratio. The differentiation defects into GABAergic neurons in patient\u2010derived cerebral organoids could be rescued by treating with either IGF1 or Gabapentin, a GABA agonist.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings provide a framework for utilizing patient\u2010derived cerebral organoids in the development of personalized pharmaceutical treatment for ASD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.70449","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T23:50:42Z","timestamp":1748908242000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Differentiation Defect Into <scp>GABAergic<\/scp> Neurons in Cerebral Organoids From Autism Patients"],"prefix":"10.1111","volume":"31","author":[{"given":"Sai","family":"Hali","sequence":"first","affiliation":[{"name":"Department of Advanced Translational Medicine, School of Medicine Konkuk University  Seoul Republic of Korea"},{"name":"NUOXINTE Biotechnology  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuerui","family":"Yao","sequence":"additional","affiliation":[{"name":"Institute of Neurology, Jiangxi Academy of Clinical Medical Sciences, Department of Neurology, the First Affiliated Hospital, Jiangxi Medical College Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo","family":"Hao","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Biotechnology and Health Sciences Wuyi University  Jiangmen China"},{"name":"Healthcare International Innovation Institute  Jiangmen China"},{"name":"Guangdong University of Technology  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe\u2010Long","family":"Jin","sequence":"additional","affiliation":[{"name":"NUOXINTE Biotechnology  Suzhou China"},{"name":"Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Biotechnology and Health Sciences Wuyi University  Jiangmen China"},{"name":"Healthcare International Innovation Institute  Jiangmen China"},{"name":"Guangdong University of Technology  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Fu","sequence":"additional","affiliation":[{"name":"Research and Development Qingdao Haier Biotech co. Ltd  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunxiao","family":"Li","sequence":"additional","affiliation":[{"name":"Research and Development Qingdao Haier Biotech co. Ltd  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Wang","sequence":"additional","affiliation":[{"name":"Research and Development Qingdao Haier Biotech co. Ltd  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heejeong","family":"Yoo","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Seoul National University College of Medicine  Seoul Republic of Korea"},{"name":"Department of Psychiatry Seoul National University Bundang Hospital  Seongnam Gyeonggi Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeonwoo","family":"La","sequence":"additional","affiliation":[{"name":"Department of Stem Cell and Regenerative Biotechnology, the Institute of Advanced Regenerative Science Konkuk University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chanhyeok","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Stem Cell and Regenerative Biotechnology, the Institute of Advanced Regenerative Science Konkuk University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwonho","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Stem Cell and Regenerative Biotechnology, the Institute of Advanced Regenerative Science Konkuk University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chan Young","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Department of Advanced Translational Medicine, School of Medicine Konkuk University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong\u2010Hun","family":"Woo","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Biology NEXEL co., Ltd  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Choongseong","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Biology NEXEL co., Ltd  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiong","family":"Jin","sequence":"additional","affiliation":[{"name":"NUOXINTE Biotechnology  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shifeng","family":"Zhu","sequence":"additional","affiliation":[{"name":"NUOXINTE Biotechnology  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenquan","family":"Zou","sequence":"additional","affiliation":[{"name":"Institute of Neurology, Jiangxi Academy of Clinical Medical Sciences, Department of Neurology, the First Affiliated Hospital, Jiangxi Medical College Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nam\u2010Hyung","family":"Kim","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Biotechnology and Health Sciences Wuyi University  Jiangmen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kee\u2010Pyo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Life Sciences College of Medicine, the Catholic University of Korea  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leshuai W.","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Life Sciences Suzhou Medical College of Soochow University  Suzhou China"},{"name":"State Key Laboratory of Radiation Medicine and Protection, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6915-8090","authenticated-orcid":false,"given":"Dong Wook","family":"Han","sequence":"additional","affiliation":[{"name":"NUOXINTE Biotechnology  Suzhou China"},{"name":"Research and Development Qingdao Haier Biotech co. Ltd  Qingdao China"},{"name":"School of Life Sciences Suzhou Medical College of Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,2]]},"reference":[{"key":"e_1_2_11_2_1","first-page":"275","article-title":"Autism Spectrum Disorder. Clinical Child","author":"AlSalehi S. M.","year":"2020","journal-title":"Neurology"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4071"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3935"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2019.146427"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2647"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.11.019"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.07.024"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.10.016"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2576"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2011.1638"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.290.3.337"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cortex.2014.10.014"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2017.09.021"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.102063"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-022-00723-9"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07935"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12517"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2008.09.002"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.04.032"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature22330"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2016.07.005"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.3163"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2012.05.009"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9896"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10637"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2018.12.015"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2021.04.006"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaz5626"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.12.051"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.00538"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.162214"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.06.034"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.332494.119"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-021-01243-6"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24358-4"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04358-6"},{"issue":"15","key":"e_1_2_11_38_1","article-title":"Modeling Neurological Diseases With Human Brain Organoids","volume":"10","author":"Wang H.","year":"2018","journal-title":"Frontiers in Synaptic Neuroscience"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110615"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202012523"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2017.86"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33364-z"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2019.10.097"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2021.102510"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0085-3"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-020-0844-z"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhu183"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2013.106"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2012.016"},{"key":"e_1_2_11_51_1","volume-title":"R: A Language and Environment for Statistical Computing [Computer Program]","year":"2021"},{"issue":"1","key":"e_1_2_11_52_1","article-title":"DAVID: A Web Server for Functional Enrichment Analysis and Functional Annotation of Gene Lists (2021 Update)","volume":"50","author":"Sherman B. T.","year":"2022","journal-title":"Nucleic Acids Research"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-24277-4"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1155\/2023\/3320211"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-4388(98)80082-2"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3777"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.2174\/1566524015666150303003028"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa052773"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.08.040"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12950"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0812394106"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2016.95"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapediatrics.2014.210"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/aur.2696"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.85145"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13229-020-00383-w"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-022-01826-x"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhaa402"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhw349"},{"issue":"3","key":"e_1_2_11_70_1","first-page":"1931","article-title":"The Number of Parvalbumin\u2010Expressing Interneurons Is Decreased in the Prefrontal Cortex in Autism","volume":"27","author":"Hashemi E.","year":"2017","journal-title":"Cerebral Cortex"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx131"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.1177\/13623613231154053"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0500-9"},{"key":"e_1_2_11_74_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.9b00106"},{"key":"e_1_2_11_75_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2014.00119"},{"key":"e_1_2_11_76_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.14103"},{"key":"e_1_2_11_77_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13064-018-0109-6"},{"key":"e_1_2_11_78_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000209175"},{"key":"e_1_2_11_79_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16953"},{"key":"e_1_2_11_80_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2017-017248"},{"key":"e_1_2_11_81_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2023.0674"},{"key":"e_1_2_11_82_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2017.00014"},{"key":"e_1_2_11_83_1","article-title":"The Role of Insulin\/IGF1 Signalling in Neurodevelopmental and Neuropsychiatric Disorders\u2013Evidence From Human Neuronal Cell Models","volume":"105330","author":"R\u00e9thelyi J. M.","year":"2023","journal-title":"Neuroscience and Biobehavioral Reviews"},{"key":"e_1_2_11_84_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adk8123"},{"key":"e_1_2_11_85_1","doi-asserted-by":"publisher","DOI":"10.1159\/000514043"},{"key":"e_1_2_11_86_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-019-0638-8"}],"container-title":["CNS Neuroscience &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cns.70449","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T08:28:50Z","timestamp":1752740930000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cns.70449"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6]]},"references-count":85,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1111\/cns.70449"],"URL":"https:\/\/doi.org\/10.1111\/cns.70449","archive":["Portico"],"relation":{},"ISSN":["1755-5930","1755-5949"],"issn-type":[{"value":"1755-5930","type":"print"},{"value":"1755-5949","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6]]},"assertion":[{"value":"2024-10-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70449"}}