{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T12:19:42Z","timestamp":1770725982135,"version":"3.49.0"},"reference-count":93,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,4,6]],"date-time":"2020-04-06T00:00:00Z","timestamp":1586131200000},"content-version":"vor","delay-in-days":96,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin &amp;amp; Trans Imm"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Bipolar disorder (BD) is a chronic disease characterised by episodes of major depression and episodes of mania or hypomania, with a worldwide prevalence of 2.4%. The cause of BD is unknown. Here, I propose the hypothesis that BD is a chronic autoimmune disease caused by Epstein\u2013Barr virus (EBV) infection of autoreactive B cells. It is postulated that EBV\u2010infected autoreactive B cells accumulate in the brain where they provide costimulatory survival signals to autoreactive T cells and differentiate into plasma cells producing pathogenic autoantibodies targeting brain components such as the N\u2010methyl\u2010D\u2010aspartate receptor. It is also proposed that the accumulation of EBV\u2010infected autoreactive B cells in the brain is a consequence of a genetically determined defect in the ability of CD8<jats:sup>+<\/jats:sup> T cells to control EBV infection. The theory is supported by studies indicating that autoimmunity, EBV infection and CD8<jats:sup>+<\/jats:sup> T\u2010cell deficiency all have roles in the pathogenesis of BD. According to the hypothesis, BD should be able to be treated by EBV\u2010specific T\u2010cell therapy and to be prevented by vaccination against EBV in early childhood. Exposure to sunlight or appropriate artificial light should also be beneficial in BD by augmenting CD8<jats:sup>+<\/jats:sup> T\u2010cell control of EBV infection.<\/jats:p>","DOI":"10.1002\/cti2.1116","type":"journal-article","created":{"date-parts":[[2020,4,6]],"date-time":"2020-04-06T12:07:55Z","timestamp":1586174875000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Hypothesis: bipolar disorder is an Epstein\u2013Barr virus\u2010driven chronic autoimmune disease \u2013 implications for immunotherapy"],"prefix":"10.1002","volume":"9","author":[{"given":"Michael P","family":"Pender","sequence":"first","affiliation":[{"name":"Faculty of Medicine The University of Queensland Brisbane QLD Australia"},{"name":"Department of Neurology Royal Brisbane and Women's Hospital Brisbane QLD Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,4,6]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.books.9780890425596"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/archgenpsychiatry.2011.12"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.36.8.585"},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2003.09.005"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2011.07.003"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2015.03.004"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2018.04.017"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-5618.2003.00024.x"},{"key":"e_1_2_15_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2006.09.011"},{"key":"e_1_2_15_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-5618.2012.01028.x"},{"key":"e_1_2_15_12_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0022-3042.2001.00728.x"},{"key":"e_1_2_15_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1300920"},{"key":"e_1_2_15_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1801490"},{"key":"e_1_2_15_15_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145708009498"},{"key":"e_1_2_15_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/bdi.12244"},{"key":"e_1_2_15_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004150070130"},{"key":"e_1_2_15_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000014419"},{"key":"e_1_2_15_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2019.01.100"},{"key":"e_1_2_15_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(01)01217-3"},{"key":"e_1_2_15_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2013.11.008"},{"key":"e_1_2_15_22_1","doi-asserted-by":"publisher","DOI":"10.2174\/1745017901511010180"},{"key":"e_1_2_15_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-5618.2011.00894.x"},{"key":"e_1_2_15_24_1","doi-asserted-by":"publisher","DOI":"10.1177\/0706743717740344"},{"key":"e_1_2_15_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eurpsy.2017.03.006"},{"key":"e_1_2_15_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2017.10.027"},{"key":"e_1_2_15_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2006.10.005"},{"key":"e_1_2_15_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2017.217"},{"key":"e_1_2_15_29_1","doi-asserted-by":"publisher","DOI":"10.5694\/j.1326-5377.2009.tb02787.x"},{"key":"e_1_2_15_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2011.10.006"},{"key":"e_1_2_15_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2012.09.035"},{"key":"e_1_2_15_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(19)30244-3"},{"key":"e_1_2_15_33_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra032015"},{"key":"e_1_2_15_34_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.2.1296-1307.2005"},{"key":"e_1_2_15_35_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000496"},{"key":"e_1_2_15_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003685"},{"key":"e_1_2_15_37_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.54.1.19"},{"key":"e_1_2_15_38_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.25.022106.141553"},{"key":"e_1_2_15_39_1","first-page":"584","article-title":"Evidence that autoimmunity in man is a Mendelian dominant trait","volume":"39","author":"Bias WB","year":"1986","journal-title":"Am J Hum Genet"},{"key":"e_1_2_15_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(90)90215-9"},{"key":"e_1_2_15_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004390050853"},{"key":"e_1_2_15_42_1","doi-asserted-by":"publisher","DOI":"10.1054\/jocn.2000.0693"},{"key":"e_1_2_15_43_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/189096"},{"key":"e_1_2_15_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trim.2005.03.021"},{"key":"e_1_2_15_45_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1086907"},{"key":"e_1_2_15_46_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20071030"},{"key":"e_1_2_15_47_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31823ed057"},{"key":"e_1_2_15_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws315"},{"key":"e_1_2_15_49_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0192109"},{"key":"e_1_2_15_50_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000466"},{"key":"e_1_2_15_51_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01699-12"},{"key":"e_1_2_15_52_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-202352"},{"key":"e_1_2_15_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38726"},{"key":"e_1_2_15_54_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2008.161018"},{"key":"e_1_2_15_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/cti.2016.87"},{"key":"e_1_2_15_56_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0706383"},{"key":"e_1_2_15_57_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458514521888"},{"key":"e_1_2_15_58_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.124714"},{"key":"e_1_2_15_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01314836"},{"key":"e_1_2_15_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-3223(91)90102-R"},{"key":"e_1_2_15_61_1","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0b013e31820f3a30"},{"key":"e_1_2_15_62_1","doi-asserted-by":"publisher","DOI":"10.3390\/v11050450"},{"key":"e_1_2_15_63_1","doi-asserted-by":"publisher","DOI":"10.1177\/1073858410381531"},{"key":"e_1_2_15_64_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458514536252"},{"key":"e_1_2_15_65_1","doi-asserted-by":"publisher","DOI":"10.1093\/ijnp\/pyu021"},{"key":"e_1_2_15_66_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2011-300213"},{"key":"e_1_2_15_67_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1984.01790120076010"},{"key":"e_1_2_15_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/0893-133X(89)90002-X"},{"key":"e_1_2_15_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2017.12.020"},{"key":"e_1_2_15_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0327(95)00081-X"},{"key":"e_1_2_15_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0327(00)00149-X"},{"key":"e_1_2_15_72_1","doi-asserted-by":"crossref","first-page":"353","DOI":"10.31887\/DCNS.2003.5.4\/bparry","article-title":"Light treatment of mood disorders","volume":"5","author":"Parry BL","year":"2003","journal-title":"Dialogues Clin Neurosci"},{"key":"e_1_2_15_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(83)92808-8"},{"key":"e_1_2_15_74_1","doi-asserted-by":"crossref","first-page":"171","DOI":"10.4049\/jimmunol.131.1.171","article-title":"Alteration of T cell subsets and induction of suppressor T cell activity in normal subjects after exposure to sunlight","volume":"31","author":"Hersey P","year":"1983","journal-title":"J Immunol"},{"key":"e_1_2_15_75_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0781.1997.tb00217.x"},{"key":"e_1_2_15_76_1","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.1999.1605"},{"key":"e_1_2_15_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-2427(93)90114-J"},{"key":"e_1_2_15_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(97)00369-X"},{"key":"e_1_2_15_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(99)70185-X"},{"key":"e_1_2_15_80_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep39479"},{"key":"e_1_2_15_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2014.02.036"},{"key":"e_1_2_15_82_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.1.322"},{"key":"e_1_2_15_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/0889-1591(87)90002-X"},{"key":"e_1_2_15_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4530(94)90023-X"},{"key":"e_1_2_15_85_1","doi-asserted-by":"publisher","DOI":"10.1159\/000026453"},{"key":"e_1_2_15_86_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458512449682"},{"key":"e_1_2_15_87_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119856"},{"key":"e_1_2_15_88_1","doi-asserted-by":"publisher","DOI":"10.1086\/523813"},{"key":"e_1_2_15_89_1","doi-asserted-by":"publisher","DOI":"10.1086\/505912"},{"key":"e_1_2_15_90_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.03.010"},{"key":"e_1_2_15_91_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aau5612"},{"key":"e_1_2_15_92_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01780-09"},{"key":"e_1_2_15_93_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830241107"},{"key":"e_1_2_15_94_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)60642-3"}],"container-title":["Clinical &amp; Translational Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcti2.1116","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cti2.1116","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cti2.1116","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cti2.1116","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T05:37:07Z","timestamp":1693805827000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cti2.1116"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1]]},"references-count":93,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,1]]}},"alternative-id":["10.1002\/cti2.1116"],"URL":"https:\/\/doi.org\/10.1002\/cti2.1116","archive":["Portico"],"relation":{},"ISSN":["2050-0068","2050-0068"],"issn-type":[{"value":"2050-0068","type":"print"},{"value":"2050-0068","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1]]},"assertion":[{"value":"2019-09-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e1116"}}