{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T07:29:08Z","timestamp":1789630148241,"version":"build-2803163510"},"reference-count":48,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,6,20]],"date-time":"2013-06-20T00:00:00Z","timestamp":1371686400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bipolar Disorders"],"published-print":{"date-parts":[[2014,8]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>Clinical staging is widespread in medicine \u2013 it informs prognosis, clinical course, and treatment, and assists individualized care. Staging places an individual on a probabilistic continuum of increasing potential disease severity, ranging from clinically at\u2010risk or latency stage through first threshold episode of illness or recurrence, and, finally, to late or end\u2010stage disease. The aim of the present paper was to examine and update the evidence regarding staging in bipolar disorder, and how this might inform targeted and individualized intervention approaches.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We provide a narrative review of the relevant information.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In bipolar disorder, the validity of staging is informed by a range of findings that accompany illness progression, including neuroimaging data suggesting incremental volume loss, cognitive changes, and a declining likelihood of response to pharmacological and psychosocial treatments. Staging informs the adoption of a number of approaches, including the active promotion of both indicated prevention for at\u2010risk individuals and early intervention strategies for newly diagnosed individuals, and the tailored implementation of treatments according to the stage of illness.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The nature of bipolar disorder implies the presence of an active process of neuroprogression that is considered to be at least partly mediated by inflammation, oxidative stress, apoptosis, and changes in neurogenesis. It further supports the concept of neuroprotection, in that a diversity of agents have putative effects against these molecular targets. Clinically, staging suggests that the at\u2010risk state or first episode is a period that requires particularly active and broad\u2010based treatment, consistent with the hope that the temporal trajectory of the illness can be altered. Prompt treatment may be potentially neuroprotective and attenuate the neurostructural and neurocognitive changes that emerge with chronicity. Staging highlights the need for interventions at a service delivery level and implementing treatments at the earliest stage of illness possible.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bdi.12099","type":"journal-article","created":{"date-parts":[[2013,6,20]],"date-time":"2013-06-20T06:40:42Z","timestamp":1371710442000},"page":"471-477","source":"Crossref","is-referenced-by-count":140,"title":["Stage managing bipolar disorder"],"prefix":"10.1111","volume":"16","author":[{"given":"Michael","family":"Berk","sequence":"first","affiliation":[{"name":"School of Medicine Deakin University Geelong"},{"name":"Department of Psychiatry University of Melbourne Melbourne Vic. Australia"},{"name":"Orygen Youth Health Melbourne Vic. Australia"},{"name":"Florey Institute for Neuroscience and Mental Health Melbourne Vic. Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lesley","family":"Berk","sequence":"additional","affiliation":[{"name":"School of Medicine Deakin University Geelong"},{"name":"Orygen Youth Health Melbourne Vic. Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seetal","family":"Dodd","sequence":"additional","affiliation":[{"name":"School of Medicine Deakin University Geelong"},{"name":"Department of Psychiatry University of Melbourne Melbourne Vic. Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sue","family":"Cotton","sequence":"additional","affiliation":[{"name":"Orygen Youth Health Melbourne Vic. Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Macneil","sequence":"additional","affiliation":[{"name":"Orygen Youth Health Melbourne Vic. Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rothanthi","family":"Daglas","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Melbourne Melbourne Vic. Australia"},{"name":"Orygen Youth Health Melbourne Vic. Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Conus","sequence":"additional","affiliation":[{"name":"Treatment and Early Intervention in Psychosis Program (TIPP) Department of Psychiatry Lausanne University Hospital Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Bechdolf","sequence":"additional","affiliation":[{"name":"Orygen Youth Health Melbourne Vic. Australia"},{"name":"Department of Psychiatry and Psychotherapy University of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Moylan","sequence":"additional","affiliation":[{"name":"School of Medicine Deakin University Geelong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gin S","family":"Malhi","sequence":"additional","affiliation":[{"name":"CADE Clinic Department of Psychiatry Royal North Shore Hospital Sydney NSW Australia"},{"name":"Discipline of Psychiatry Sydney Medical School The University of Sydney Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,6,20]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1614.2006.01860.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-5618.2007.00484.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.bp.111.107797"},{"key":"e_1_2_8_5_1","first-page":"S36","article-title":"From neuroprogression to neuroprotection: implications for clinical care","volume":"193","author":"Berk M","year":"2010","journal-title":"Med J Aust"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2007.03.007"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/13651500410005423"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/070674371005500803"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0447.1993.tb03362.x"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1586\/ern.09.31"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2007.04.003"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.149.2.191"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpedi.158.5.478"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1159\/000116606"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198911303212201"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.156.8.1264"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004060050091"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-5618.2011.00889.x"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1177\/0004867412460593"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-5618.2009.00724.x"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.188.4.313"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2009.09.009"},{"issue":"1","key":"e_1_2_8_23_1","first-page":"20","article-title":"Long\u2010term follow up of psychotherapies in bipolar disorder","volume":"10","author":"Colom F","year":"2008","journal-title":"Bipolar Disord"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-7893.2011.00336.x"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2010.10.001"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1971"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-5618.2011.00927.x"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-5618.2010.00835.x"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.159.11.1841"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-5618.2006.00284.x"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0447.2007.01069.x"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2008.06.009"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-5618.2001.030206.x"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-5618.2006.00277.x"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.149.8.999"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2007.10.005"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2008.05.001"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/hup.390"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145708009310"},{"key":"e_1_2_8_40_1","first-page":"263","article-title":"3\u2010Nitrotyrosine and glutathione antioxidant system in patients in the early and late stages of bipolar disorder","volume":"34","author":"Andreazza AC","year":"2009","journal-title":"J Psychiatry Neurosci"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2012.33"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2010.06.016"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161212799316226"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2011.06.043"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2007.01.027"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-5618.2010.00872.x"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1586\/ern.11.174"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-7893.2011.00273.x"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-5618.2011.00942.x"}],"container-title":["Bipolar Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbdi.12099","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bdi.12099","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T15:58:57Z","timestamp":1694447937000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bdi.12099"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,6,20]]},"references-count":48,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2014,8]]}},"alternative-id":["10.1111\/bdi.12099"],"URL":"https:\/\/doi.org\/10.1111\/bdi.12099","archive":["Portico"],"relation":{},"ISSN":["1398-5647","1399-5618"],"issn-type":[{"value":"1398-5647","type":"print"},{"value":"1399-5618","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,6,20]]}}}