{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T13:01:51Z","timestamp":1775307711111,"version":"3.50.1"},"reference-count":57,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,11,13]],"date-time":"2018-11-13T00:00:00Z","timestamp":1542067200000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Psychopharmacology"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Previous evidence suggested the involvement of serotonin transporter (<jats:italic>SLC6A4<\/jats:italic>) and activity regulated cytoskeleton\u2010associated protein (<jats:italic>ARC<\/jats:italic>) in antidepressant action. This study investigated their role in antidepressant efficacy and treatment\u2010resistant depression (TRD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Three samples (<jats:italic>n<\/jats:italic> total\u00a0=\u00a0648) were investigated to test the association between treatment outcomes (response, remission, symptom improvement, and TRD) and 11 polymorphisms within <jats:italic>SLC6A4<\/jats:italic> and <jats:italic>ARC<\/jats:italic> genes. The possible modulating effect of age and gender was considered. Response and remission were also investigated using a fixed\u2010effects meta\u2010analysis of the three samples.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>SLC6A4<\/jats:italic> 5\u2010HTTLPR\/rs25531 effects on symptom improvement were modulated by age (better improvement in L\/LA carriers in older subjects) and gender (better improvement in L\/LA female carriers). <jats:italic>SLC6A4<\/jats:italic> STin2 long alleles were associated with remission and lower risk of TRD. Preliminary evidence of association between <jats:italic>ARC<\/jats:italic> rs11167152\/rs10110456 and different outcomes was found.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>5\u2010HTTLPR\/rs25531 effect on antidepressant efficacy was modulated by age, in line with previous literature data. STin2 effect on antidepressant efficacy was in line with previous meta\u2010analyses. A new possible effect of ARC variants on antidepressant efficacy was observed; however, further studies in larger samples are needed to confirm their role.<\/jats:p><\/jats:sec>","DOI":"10.1002\/hup.2682","type":"journal-article","created":{"date-parts":[[2018,11,14]],"date-time":"2018-11-14T05:15:23Z","timestamp":1542172523000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The serotonin transporter and the activity regulated cytoskeleton\u2010associated protein genes in antidepressant response and resistance: <scp>5\u2010HTTLPR<\/scp> and other variants"],"prefix":"10.1002","volume":"33","author":[{"given":"Marco","family":"Calabr\u00f2","sequence":"first","affiliation":[{"name":"Department of Biomedical and Dental Sciences and Morphofunctional Images, Division of Medical Biotechnologies and Preventive Medicine University of Messina  Messina Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Fabbri","sequence":"additional","affiliation":[{"name":"Department of Biomedical and NeuroMotor Sciences University of Bologna  Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Concetta","family":"Crisafulli","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Dental Sciences and Morphofunctional Images, Division of Medical Biotechnologies and Preventive Medicine University of Messina  Messina Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diego","family":"Albani","sequence":"additional","affiliation":[{"name":"Laboratory of Biology of Neurodegenerative Disorders, Neuroscience Department IRCCS Istituto di Ricerche Farmacologiche \u201cMario Negri\u201d  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianluigi","family":"Forloni","sequence":"additional","affiliation":[{"name":"Laboratory of Biology of Neurodegenerative Disorders, Neuroscience Department IRCCS Istituto di Ricerche Farmacologiche \u201cMario Negri\u201d  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siegfried","family":"Kasper","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy Medical University Vienna  Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonina","family":"Sidoti","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Dental Sciences and Morphofunctional Images, Division of Medical Biotechnologies and Preventive Medicine University of Messina  Messina Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elvira","family":"Velardi","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Dental Sciences and Morphofunctional Images, Division of Medical Biotechnologies and Preventive Medicine University of Messina  Messina Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Zohar","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Sheba Medical Center, Tel Hashomer, and Sackler School of Medicine Tel Aviv University  Tel Aviv Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alzbeta","family":"Juven\u2010Wetzler","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Sheba Medical Center, Tel Hashomer, and Sackler School of Medicine Tel Aviv University  Tel Aviv Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Souery","sequence":"additional","affiliation":[{"name":"Laboratoire de Psychologie Medicale, Universit\u00e8 Libre de Bruxelles and Psy Pluriel Centre Europ\u00e9en de Psychologie Medicale  Brussels Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stuart","family":"Montgomery","sequence":"additional","affiliation":[{"name":"Imperial College, University of London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julien","family":"Mendlewicz","sequence":"additional","affiliation":[{"name":"School of Medicine, Free University of Brussels  Brussels Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4363-3759","authenticated-orcid":false,"given":"Alessandro","family":"Serretti","sequence":"additional","affiliation":[{"name":"Department of Biomedical and NeuroMotor Sciences University of Bologna  Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,11,13]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2014.05.015"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bth457"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/07853890701769728"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2010.04.020"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg616"},{"issue":"2","key":"e_1_2_7_7_1","first-page":"651","article-title":"Current understanding of the neurobiology of major depressive disorder","volume":"56","author":"Chirita A. L.","year":"2015","journal-title":"Romanian Journal of Morphology and Embryology"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2014.00189"},{"issue":"3","key":"e_1_2_7_9_1","first-page":"415","article-title":"Serotoninergic system and limbic\u2010hypothalamic\u2010pituitary\u2010adrenal axis (LHPA axis) in depression","volume":"40","author":"Cubala W. J.","year":"2006","journal-title":"Psychiatria Polska"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.22555"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.2515\/therapie:2005066"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2016.04.034"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)31678-6"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2015.06.011"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2013.05.020"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1073774"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.20056"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1366"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/YIC.0000000000000101"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2017.00117"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1086\/503850"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.64.7.783"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.bp.108.062521"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0088031"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-016-0385-9"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2015.00279"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2012.09.057"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(95)90299-6"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.26.15251"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-016-2099-9"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1177\/0897190011426972"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2883-07.2007"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.116.233338"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-008-1276-7"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2007.08.016"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2013.05.011"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpediatrics.2010.51"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2013.13020185"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1006546107"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2011.10.003"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.2174\/13894501113149990209"},{"issue":"2","key":"e_1_2_7_42_1","first-page":"157","article-title":"Antidepressant\u2010resistant depression and the bipolar spectrum\u2014Diagnostic and therapeutic considerations","volume":"31","author":"Rihmer Z.","year":"2016","journal-title":"Psychiatria Hungarica"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1161\/str.36.9.1879"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2012.02.006"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jagp.2012.10.012"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jagp.2013.02.012"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl171"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.3109\/15622975.2014.987814"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v68n0713"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-183X.2008.00390.x"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001326"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.163.1.28"},{"key":"e_1_2_7_53_1","doi-asserted-by":"crossref","unstructured":"Viechtbauer W.(2010).Conducting Meta\u2010Analyses in R with the Metafor Package. 2010 36(3) 48.https:\/\/doi.org\/10.18637\/jss.v036.i03","DOI":"10.18637\/jss.v036.i03"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2012.03.031"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X14666160202121111"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2013.00180"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2015.03.014"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2009.04.030"}],"container-title":["Human Psychopharmacology: Clinical and Experimental"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhup.2682","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hup.2682","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T15:57:47Z","timestamp":1694793467000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/hup.2682"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11]]},"references-count":57,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2018,11]]}},"alternative-id":["10.1002\/hup.2682"],"URL":"https:\/\/doi.org\/10.1002\/hup.2682","archive":["Portico"],"relation":{},"ISSN":["0885-6222","1099-1077"],"issn-type":[{"value":"0885-6222","type":"print"},{"value":"1099-1077","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11]]},"assertion":[{"value":"2017-10-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-11-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2682"}}