{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T12:19:30Z","timestamp":1784809170219,"version":"3.55.0"},"reference-count":64,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T00:00:00Z","timestamp":1728950400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T00:00:00Z","timestamp":1728950400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP20KK0194"],"award-info":[{"award-number":["JP20KK0194"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP21K07545"],"award-info":[{"award-number":["JP21K07545"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"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":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropsychopharm Rep"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Social anxiety disorder (SAD) is a common disorder characterized by excessive fear of scrutiny and embarrassment, leading to severe distress and avoidance behaviors or dysfunctions. SAD and other relevant diseases have been reported to be associated with a higher risk of aging\u2010related diseases, such as Alzheimer's disease, Parkinson's disease, and diabetes mellitus. Recently, epigenetic clock analysis, which measures biological aging based on comprehensive DNA methylation (DNAm) status, has been widely conducted. We conducted epigenetic clock analyses in patients with SAD and controls, examining various epigenetic age acceleration and DNAm\u2010based predictive values of aging\u2010related proteins (GrimAge components and GrimAge2 components), including leptin level.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used the publicly available DNAm dataset, GSE164056, which consists of 66 patients with SAD and 77 controls of Caucasian descent aged between 18 and 50\u2009years. We conducted regression analyses investigating the association between SAD and various indices of epigenetic aging, using age and sex as covariates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      None of the epigenetic clocks showed significant differences in age acceleration. Of the DNAm\u2010based predictive values of aging\u2010related proteins, leptin level in GrimAge components (\n                      <jats:italic>q<\/jats:italic>\n                      \u2009=\u20090.0123) and GrimAge2 components (\n                      <jats:italic>q<\/jats:italic>\n                      \u2009=\u20090.0123) were significantly lower in patients with SAD than in controls.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The results of this study suggested that leptin may be involved in SAD pathogenesis as an aging\u2010related protein. Therefore, further studies with different designs are required.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/npr2.12487","type":"journal-article","created":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T06:35:13Z","timestamp":1728974113000},"page":"774-783","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Biological aging analysis based on DNA methylation status for social anxiety disorder"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-0361-6474","authenticated-orcid":false,"given":"Nobuhiko","family":"Noguchi","sequence":"first","affiliation":[{"name":"Department of Psychiatry Yokohama City University Graduate School of Medicine  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2058-1678","authenticated-orcid":false,"given":"Toshiyuki","family":"Shirai","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Kobe University Graduate School of Medicine  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Suda","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yokohama City University Graduate School of Medicine  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saki","family":"Hattori","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yokohama City University Graduate School of Medicine  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatoshi","family":"Miyauchi","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yokohama City University Graduate School of Medicine  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5953-5526","authenticated-orcid":false,"given":"Satoshi","family":"Okazaki","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Kobe University Graduate School of Medicine  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junichi","family":"Fujita","sequence":"additional","affiliation":[{"name":"Psychiatry Center of Yokohama City University Medical Center  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Asami","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yokohama City University Graduate School of Medicine  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikuo","family":"Otsuka","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Kobe University Graduate School of Medicine  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akitoyo","family":"Hishimoto","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Kobe University Graduate School of Medicine  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,15]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291707001699"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1992.01820040025003"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/da.20543"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2006.05.043"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2015.2"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-5949.2008.00051.x"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.11.001"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.202454"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2012.10.016"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-015-0584-6"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101414"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101684"},{"issue":"23","key":"e_1_2_11_14_1","first-page":"9484","article-title":"DNA methylation GrimAge version 2","volume":"14","author":"Lu AT","year":"2022","journal-title":"Aging"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-017-0048-8"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2018.17060595"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2019.109805"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41514-023-00117-1"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2023.115103"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.100859"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.100864"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2013-14-10-r115"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101508"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161282004140213160930"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.102173"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.73420"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajhb.23488"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)60488-2"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/wcs.1390"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.28575"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2021.03.039"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1089\/jayao.2021.0050"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychores.2014.11.023"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2020.113074"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1080\/16506073.2024.2331188"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10802-022-00996-0"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-03599-8"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-021-01225-w"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/da.20503"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-13-86"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05580-6"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2024.02.012"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2019.04.059"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1007616"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-021-01756-2"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI91578"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19980615)395:4<535::AID-CNE9>3.0.CO;2-2"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2016.00137"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10287"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-019-0228-0"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00787-013-0441-7"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161212803530907"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0597-575"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1515\/jpem-2019-0229"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1097\/GME.0000000000001210"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcn.12922"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2015.06.012"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1159\/000500737"},{"issue":"1","key":"e_1_2_11_59_1","first-page":"9","article-title":"Intracerebroventricular administration of leptin increases anxiety\u2010like behavior in female rats after semi\u2010starvation \u2013 implications for anxiety in eating disorders","volume":"55","author":"Yamauchi T","year":"2009","journal-title":"Osaka City Med J"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0166843"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2005.01420.x"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.117.309451"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0543-y"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0263478"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2020.01.015"}],"container-title":["Neuropsychopharmacology Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/npr2.12487","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/npr2.12487","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/npr2.12487","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T23:37:14Z","timestamp":1773013034000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/npr2.12487"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,15]]},"references-count":64,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1002\/npr2.12487"],"URL":"https:\/\/doi.org\/10.1002\/npr2.12487","archive":["Portico"],"relation":{},"ISSN":["2574-173X","2574-173X"],"issn-type":[{"value":"2574-173X","type":"print"},{"value":"2574-173X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,15]]},"assertion":[{"value":"2024-06-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}