{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T18:56:03Z","timestamp":1792522563812,"version":"4.5.0"},"reference-count":85,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate genes associated with palmitoylation modification implicated in generalized anxiety disorder (GAD), and to elucidate the mechanistic roles of these genes via immune cell\u2010mediated pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Utilizing large\u2010scale genetic datasets, genes categorized as palmitoylation\u2010expression quantitative trait loci (eQTL) were identified by intersecting palmitoylation\u2010related genes (as compiled from the most recent reviews) with genome\u2010wide eQTL datasets. A two\u2010sample Mendelian randomization (MR) methodology was applied to investigate the causal relationship between palmitoylation\u2010eQTL genes and GAD, with further verification conducted through summary\u2010data\u2010based Mendelian randomization (SMR) to establish the final target genes. Subsequently, the underlying mechanisms of these genes were examined through immune cell\u2010mediated processes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Twenty\u2010two palmitoylation\u2010eQTL gene loci were identified, among which five demonstrated a notable link to GAD: PPT2 (odds ratio [OR] = 0.844,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.007), ZDHHC5 (OR = 1.101,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.017), ZDHHC13 (OR = 1.175,\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001), ZDHHC20 (OR = 0.874,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.003), and ZDHHC24 (OR = 0.806,\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001). ZDHHC5 and ZDHHC13 were validated as final target genes through SMR analysis. Mediation MR analysis revealed that SSC\u2010A on CD4+ T cells (mediation proportion: 36.4%) served as a mediating factor for ZDHHC5.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The findings indicate that ZDHHC5 contributes to the pathogenesis of GAD by modulating SSC\u2010A on CD4+ T cells, thereby offering novel targets for the investigation of GAD pathophysiology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.70818","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T05:45:17Z","timestamp":1756878317000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["ZDHHC5 Mediates Immune Dysregulation Driving Generalized Anxiety Disorder Risk"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0096-064X","authenticated-orcid":false,"given":"Fuqiang","family":"Sun","sequence":"first","affiliation":[{"name":"College of Acupuncture and Tuina Shandong University of Traditional Chinese Medicine  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gengchen","family":"Lu","sequence":"additional","affiliation":[{"name":"College of Acupuncture and Tuina Shandong University of Traditional Chinese Medicine  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nannan","family":"Li","sequence":"additional","affiliation":[{"name":"Independent Researcher Xiamen Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Dai","sequence":"additional","affiliation":[{"name":"College of Acupuncture and Tuina Shandong University of Traditional Chinese Medicine  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Ren","sequence":"additional","affiliation":[{"name":"College of Acupuncture and Tuina Shandong University of Traditional Chinese Medicine  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruimin","family":"Ma","sequence":"additional","affiliation":[{"name":"College of Acupuncture and Tuina Shandong University of Traditional Chinese Medicine  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifei","family":"Feng","sequence":"additional","affiliation":[{"name":"College of Acupuncture and Tuina Shandong University of Traditional Chinese Medicine  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Zong","sequence":"additional","affiliation":[{"name":"College of Acupuncture and Tuina Shandong University of Traditional Chinese Medicine  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Acupuncture Affiliated Hospital of Shandong University of Traditional Chinese Medicine  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.4.2068"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.books.9780890425596"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2013.1111"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.258186"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0962\u20108924(02)00008\u20109"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/00006842\u2010199905000\u201000019"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyy101"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2008.08010089"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.12688\/wellcomeopenres.15555.3"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/0962280215597579"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380\u2010018\u20100235\u2010x"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10654\u2010021\u201000757\u20101"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.867189"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00032.2014"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.2018.66"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1337478"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10238\u2010024\u201001429\u20106"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M404410200"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2016.06.008"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(21)02143\u20107"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)42253-3"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2297"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k601"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.7326\/aitc201904020"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.17219"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2011.04.005"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010024\u201000700\u20108"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.10.001"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570159x15666171123201142"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2013.04.060"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.2.913"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.22506"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974\u2010020\u201001899\u2010x"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2018.05.026"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy163"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12888\u2010016\u20100946\u2010y"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2017.01.021"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.6b00750"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.30122"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/mpr.1359"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201846666"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD012942.pub2"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2021.612471"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2022.08.005"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010022\u201005473\u20108"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00150"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1042\/bst20140270"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12182209"},{"key":"e_1_2_10_50_1","first-page":"617","article-title":"Diagnosis and Management of Generalized Anxiety Disorder and Panic Disorder in Adults","volume":"91","author":"Locke A. B.","year":"2015","journal-title":"American Family Physician"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102014\u201004\u2010571331"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau6391"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2016.146"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2015.5"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11920\u2010022\u201001326\u20103"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00328"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11932"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2018.08.017"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398\u2010021\u201001742\u20108"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharep.2014.08.006"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2006.03.010"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588\u2010020\u20100684\u20104"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2018.12.131"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2023.3971"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12376"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(21)00359\u20107"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2015.05.018"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.73.011303.073954"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2017.08.082"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035\u2010025\u201004764\u20101"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.100311"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M601530200"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2010.07.002"},{"key":"e_1_2_10_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2014.05.007"},{"key":"e_1_2_10_75_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440\u20101819.2008.01905.x"},{"key":"e_1_2_10_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2013.27"},{"key":"e_1_2_10_77_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11481\u2010022\u201010056\u20105"},{"key":"e_1_2_10_78_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.15709"},{"key":"e_1_2_10_79_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035\u2010023\u201003832\u20108"},{"key":"e_1_2_10_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2017.07.021"},{"key":"e_1_2_10_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2023.101174"},{"key":"e_1_2_10_82_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2018.00175"},{"key":"e_1_2_10_83_1","doi-asserted-by":"publisher","DOI":"10.1002\/1878\u20100261.13308"},{"key":"e_1_2_10_84_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2022.858989"},{"key":"e_1_2_10_85_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3538"},{"key":"e_1_2_10_86_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.727475"}],"container-title":["Brain and Behavior"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/brb3.70818","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/brb3.70818","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/brb3.70818","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T16:42:32Z","timestamp":1777480952000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/brb3.70818"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":85,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1002\/brb3.70818"],"URL":"https:\/\/doi.org\/10.1002\/brb3.70818","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/BRB3.70818\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BRB3.70818\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BRB3.70818\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BRB3.70818\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BRB3.70818\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BRB3.70818\/v1\/review2","asserted-by":"object"}]},"ISSN":["2162-3279","2162-3279"],"issn-type":[{"value":"2162-3279","type":"print"},{"value":"2162-3279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9]]},"assertion":[{"value":"2025-06-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70818"}}