{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T20:50:12Z","timestamp":1792702212584,"version":"4.5.0"},"reference-count":80,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T00:00:00Z","timestamp":1643846400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Approximately 1 in 36 children are diagnosed with autism spectrum disorder (ASD). The disorder is four times more common in males than in females. Zinc deficiency and mutations in\n                    <jats:italic>SHANK2<\/jats:italic>\n                    and\n                    <jats:italic>SHANK3<\/jats:italic>\n                    (members of a family of excitatory postsynaptic scaffolding proteins) are all risk factors that may contribute to the pathophysiology of the disease. The presence of shankopathies (loss of one copy of the\n                    <jats:italic>SHANK3<\/jats:italic>\n                    gene) can lead to the development of Phelan\u2010McDermid syndrome (PMDS)\u2014a rare genetic disorder characterized by developmental delay, intellectual disability, poor motor tone, and ASD\u2010like symptoms. We reviewed the relationship between zinc, ASD, and PMDS as well as the effect of zinc supplementation in improving symptoms of ASD and PMDS based on 22 studies published within 6\u00a0years (2015\u20132020). Zinc deficiency (assessed by either dietary intake, blood, hair, or tooth matrix) was shown to be highly prevalent in ASD and PMDS patients as well as in preclinical models of ASD and PMDS. Zinc supplements improved the behavioral deficits in animal models of ASD and PMDS. Clinical trials are still needed to validate the beneficial therapeutic effects of zinc supplements in ASD and PMDS patients.\n                  <\/jats:p>","DOI":"10.1002\/jnr.25019","type":"journal-article","created":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T12:14:37Z","timestamp":1643890477000},"page":"970-978","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Zinc deficiency and supplementation in autism spectrum disorder and\n                    <scp>Phelan\u2010McDermid<\/scp>\n                    syndrome"],"prefix":"10.1002","volume":"100","author":[{"given":"Hadeil M.","family":"Alsufiani","sequence":"first","affiliation":[{"name":"Biochemistry Department, Faculty of Sciences King Abdulaziz University Jeddah Saudi Arabia"},{"name":"Experimental Biochemistry Unit, King Fahad Medical Research Center King Abdulaziz University Jeddah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa S.","family":"Alkhanbashi","sequence":"additional","affiliation":[{"name":"Biochemistry Department, Faculty of Sciences King Abdulaziz University Jeddah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norah A. Bin","family":"Laswad","sequence":"additional","affiliation":[{"name":"Biochemistry Department, Faculty of Sciences King Abdulaziz University Jeddah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khulood K.","family":"Bakhadher","sequence":"additional","affiliation":[{"name":"Biochemistry Department, Faculty of Sciences King Abdulaziz University Jeddah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shareefa A.","family":"Alghamdi","sequence":"additional","affiliation":[{"name":"Biochemistry Department, Faculty of Sciences King Abdulaziz University Jeddah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haythum O.","family":"Tayeb","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Internal Medicine The Neuroscience Research Unit King Abdulaziz University Jeddah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank I.","family":"Tarazi","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neuroscience Harvard Medical School and McLean Hospital Belmont Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,2,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2346"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.13005\/bpj\/1909"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0270(01)00415-0"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15493"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10803-016-2963-6"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.589"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/syn.20683"},{"issue":"2","key":"e_1_2_11_9_1","doi-asserted-by":"crossref","first-page":"225","DOI":"10.55782\/ane-2013-1932","article-title":"The role of zinc and copper in autism spectrum disorders","volume":"73","author":"Bj\u00f8rklund G.","year":"2013","journal-title":"Acta Neurobiologiae Experimentalis (Wars)"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1086\/321293"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2009.06.003"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.20308"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.10035"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0031-9384(87)90105-3"},{"key":"e_1_2_11_15_1","unstructured":"Centers for Disease Control and Prevention 2018"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2018.02.008"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1111097"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2008.08.022"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-016-9823-0"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aat1293"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008X(91)90046-H"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1933"},{"issue":"2","key":"e_1_2_11_23_1","first-page":"40","article-title":"Nutritional and metabolic biomarkers in autism spectrum disorders: An exploratory study","volume":"14","author":"Esparham A. E.","year":"2015","journal-title":"Integrative Medicine: A Clinician's Journal"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/13547500902783747"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2018.00374"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2016.00027"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2011.07.003"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2016.00037"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2017.00450"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt303"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnsyn.2018.00011"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)09551-X"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12011-020-02146-3"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.2006.163.7.1252"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2005.03.040"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1097\/HRP.0000000000000029"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genom-091212-153431"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/aur.1529"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(74)90079-3"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2013.278"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23089"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2015.02.027"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1159\/000290040"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/1866-1955-6-39"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2013.11.005"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002521"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004580"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9054"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu8050294"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyt282"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.3889\/oamjms.2015.051"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1086\/522590"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1100323108"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2014.03.007"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-020-00169-1"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09965"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep45190"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09146"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10803-017-3271-5"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2018.10.054"},{"issue":"2","key":"e_1_2_11_61_1","first-page":"144","article-title":"Zinc and its importance for human health: An integrative review","volume":"18","author":"Roohani N.","year":"2013","journal-title":"Journal of Research in Medical Sciences"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.4137\/NMI.S8761"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1515\/revneuro-2017-0015"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10534-017-0033-y"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncir.2019.00006"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2018.05.007"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jand.2018.05.005"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.107700"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtemb.2020.126539"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(92)90494-M"},{"key":"e_1_2_11_71_1","first-page":"77","article-title":"Hair heavy metal and essential trace element concentration in children with autism spectrum disorder","volume":"248","author":"Tabatadze T.","year":"2015","journal-title":"Georgian Medical News"},{"issue":"4","key":"e_1_2_11_72_1","first-page":"908","article-title":"Tumor necrosis factor\u2010\u03b1 alters maternal and embryonic zinc metabolism and is developmentally toxic in mice","volume":"125","author":"Taubeneck M. W.","year":"1995","journal-title":"Journal of Nutrition"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.29245\/2572.942X\/2017\/10.1158"},{"key":"e_1_2_11_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.06.174"},{"key":"e_1_2_11_75_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-020-00650-0"},{"issue":"1","key":"e_1_2_11_76_1","first-page":"1","article-title":"Altered mGluR5\u2010Homer scaffolds and corticostriatal connectivity in a Shank3 complete knockout model of autism","volume":"7","author":"Wang X.","year":"2016","journal-title":"Nature Communications"},{"key":"e_1_2_11_77_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11208"},{"issue":"1","key":"e_1_2_11_78_1","first-page":"113","article-title":"Molecular characterization of a 130\u2010kb terminal microdeletion at 22q in a child with mild mental retardation","volume":"60","author":"Wong A.","year":"1997","journal-title":"American Journal of Human Genetics"},{"key":"e_1_2_11_79_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12011-018-1615-4"},{"key":"e_1_2_11_80_1","doi-asserted-by":"publisher","DOI":"10.3109\/14767058.2015.1079615"},{"key":"e_1_2_11_81_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12011-018-1466-z"}],"updated-by":[{"DOI":"10.1002\/jnr.70128","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000}}],"container-title":["Journal of Neuroscience Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jnr.25019","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jnr.25019","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jnr.25019","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,17]],"date-time":"2024-09-17T17:03:18Z","timestamp":1726592598000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jnr.25019"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,3]]},"references-count":80,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022,4]]}},"alternative-id":["10.1002\/jnr.25019"],"URL":"https:\/\/doi.org\/10.1002\/jnr.25019","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/JNR.25019\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.25019\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.25019\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.25019\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.25019\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.25019\/v1\/review2","asserted-by":"object"}]},"ISSN":["0360-4012","1097-4547"],"issn-type":[{"value":"0360-4012","type":"print"},{"value":"1097-4547","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,3]]},"assertion":[{"value":"2021-06-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}