{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T04:04:44Z","timestamp":1767585884644},"reference-count":122,"publisher":"Cambridge University Press (CUP)","issue":"2","license":[{"start":{"date-parts":[[2011,5,18]],"date-time":"2011-05-18T00:00:00Z","timestamp":1305676800000},"content-version":"unspecified","delay-in-days":1447,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epidemiol Psichiatr Soc"],"published-print":{"date-parts":[[2007,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Longitudinal assessment of the course of major psychiatric disorders has been advanced by studies from onset, but only rarely have large numbers of patients with a range of psychotic and major affective disorders been studied simultaneously and systematically from illness-onset. The decade-long McLean-Harvard First Episode Project &amp; International Consortium for Bipolar Disorder Research has systematically followed-up large numbers of patients with DSM-IV bipolar or psychotic disorders from first hospitalization. Major findings among patients with bipolar I disorder include: [a] full functional recovery from initial episodes was uncommon, and full symptomatic recovery, much slower than early syndromal recovery; [b] risks of relapse, recurrence, and switching were very high in the first two years; [c] most early morbidity was depressive-dysphoric, as reported in mid-course; [d] initial depression or mixed-states predicted more later depressive and overall morbidity, whereas initial mania or psychosis predicted later mania and a better prognosis; [e] based on within-subject modeling, most patients did not show progressive cycling over time, and illness-course was rather chaotic within and among patients; [f] treatment-latency or episode-counts were unassociated with responsiveness to long-term mood-stabilizing treatment; [g] very high rates of suicidal behavior and accidents occurred early; [h] early substance-use comorbidity associated with anxiety; [i] factor-analysis of prodromal symptoms predicted bipolar disorder much better than non-affective psychotic disorders. Project findings indicate that the course of bipolar I disorder is much less favorable than had been believed formerly, despite clinical treatment with modern mood-stabilizing and other treatments.<\/jats:p>","DOI":"10.1017\/s1121189x00004711","type":"journal-article","created":{"date-parts":[[2017,2,20]],"date-time":"2017-02-20T11:27:30Z","timestamp":1487590050000},"page":"109-117","source":"Crossref","is-referenced-by-count":40,"title":["Longitudinal research on bipolar disorders"],"prefix":"10.1017","volume":"16","author":[{"given":"Paola","family":"Salvatore","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mauricio","family":"Tohen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hari-Mandir","family":"Kaur Khalsa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Baethge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonardo","family":"Tondo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ross J.","family":"Baldessarini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"56","published-online":{"date-parts":[[2011,5,18]]},"reference":[{"key":"S1121189X00004711_ref112","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0447.2003.00126.x"},{"key":"S1121189X00004711_ref110","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.178.41.s184"},{"key":"S1121189X00004711_ref109","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.160.12.2099"},{"key":"S1121189X00004711_ref108","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.157.2.220"},{"key":"S1121189X00004711_ref107","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(00)00915-X"},{"key":"S1121189X00004711_ref103","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1990.01810240026005"},{"key":"S1121189X00004711_ref101","first-page":"301","volume-title":"Textbook in Psychiatric Epidemiology","author":"Tohen","year":"1995"},{"key":"S1121189X00004711_ref099","first-page":"127","volume-title":"Psychiatric Treatment Advances in Outcome Research","author":"Tohen","year":"1991"},{"key":"S1121189X00004711_ref097","doi-asserted-by":"publisher","DOI":"10.2165\/00023210-200115090-00004"},{"key":"S1121189X00004711_ref096","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.55.1.49"},{"key":"S1121189X00004711_ref093","doi-asserted-by":"publisher","DOI":"10.1007\/BF00585315"},{"key":"S1121189X00004711_ref086","doi-asserted-by":"publisher","DOI":"10.1053\/comp.2002.34629"},{"key":"S1121189X00004711_ref084","first-page":"25","article-title":"Medical risk in patients with bipolar disorder and schizophrenia","volume":"67","author":"Newcomer","year":"2006","journal-title":"Journal of Clinical Psychiatry"},{"key":"S1121189X00004711_ref082","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2004.02.012"},{"key":"S1121189X00004711_ref080","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-9964(99)00125-5"},{"key":"S1121189X00004711_ref081","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2006.11.007"},{"key":"S1121189X00004711_ref079","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291798006771"},{"key":"S1121189X00004711_ref076","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1993.01820170047006"},{"key":"S1121189X00004711_ref027","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2003.09.003"},{"key":"S1121189X00004711_ref073","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.58.2.158"},{"key":"S1121189X00004711_ref064","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.155.5.646"},{"key":"S1121189X00004711_ref056","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1781(94)02576-X"},{"key":"S1121189X00004711_ref060","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.59.6.530"},{"key":"S1121189X00004711_ref111","doi-asserted-by":"publisher","DOI":"10.2165\/00023210-200317070-00003"},{"key":"S1121189X00004711_ref052","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0327(96)00082-1"},{"key":"S1121189X00004711_ref057","doi-asserted-by":"publisher","DOI":"10.1046\/j.1399-5618.2003.00091.x"},{"key":"S1121189X00004711_ref048","first-page":"3","article-title":"Cognitive impairment and functional outcome in schizophrenia and bipolar disorder","volume":"67","author":"Green","year":"2006","journal-title":"Journal of Clinical Psychiatry"},{"key":"S1121189X00004711_ref061","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1982.04290010048009"},{"key":"S1121189X00004711_ref044","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0327(03)00161-7"},{"key":"S1121189X00004711_ref072","unstructured":"Khalsa H.K. , Salvatore P. , Baethge C. , Hennen J. , Tohen M. & Baldessarini R.J. (in press). Suicidal events and accidents in 216 first-episode bipolar-I disorder patients: Predictive factors. Journal of Affective Disorders."},{"key":"S1121189X00004711_ref043","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1176\/ajp.152.11.1635","article-title":"Relapse and impairment in bipolar disorder","volume":"152","author":"Gitlin","year":"1995","journal-title":"American Journal of Psychiatry"},{"key":"S1121189X00004711_ref051","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-68405-0"},{"key":"S1121189X00004711_ref038","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0327(95)00073-9"},{"key":"S1121189X00004711_ref071","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291797005333"},{"key":"S1121189X00004711_ref033","first-page":"5","article-title":"Correlates of suicidal behavior and lithium treatment in bipolar disorder","volume":"65","author":"Dunner","year":"2004","journal-title":"Journal of Clinical Psychiatry"},{"key":"S1121189X00004711_ref087","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v64n0610"},{"key":"S1121189X00004711_ref032","doi-asserted-by":"publisher","DOI":"10.3109\/10401239709147780"},{"key":"S1121189X00004711_ref028","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-5618.2006.00315.x"},{"key":"S1121189X00004711_ref009","first-page":"429","volume-title":"In Goodman and Gilman's The Pharmacological Basis of Therapeutics","author":"Baldessarini","year":"2005"},{"key":"S1121189X00004711_ref095","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v65n0802"},{"key":"S1121189X00004711_ref026","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-5618.2004.00171.x"},{"key":"S1121189X00004711_ref014","first-page":"277","volume-title":"In Textbook of Suicide Assessment and Management","author":"Baldessarini","year":"2006"},{"key":"S1121189X00004711_ref046","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.8.1.13"},{"key":"S1121189X00004711_ref024","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.157.2.213"},{"key":"S1121189X00004711_ref058","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.157.2.182"},{"key":"S1121189X00004711_ref078","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1111\/j.1600-0447.1989.tb03032.x","article-title":"The Scottish first episode schizophrenia study. VII. Two-year follow-up","volume":"80","author":"McCreadie","year":"1989","journal-title":"Acta Psychiatrica Scandinavica"},{"key":"S1121189X00004711_ref035","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2006.09.013"},{"key":"S1121189X00004711_ref090","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2006.04.008"},{"key":"S1121189X00004711_ref021","doi-asserted-by":"publisher","DOI":"10.1080\/hrp.11.5.245.256"},{"key":"S1121189X00004711_ref020","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1988.01800270040005"},{"key":"S1121189X00004711_ref041","doi-asserted-by":"publisher","DOI":"10.1046\/j.1399-5618.2003.00074.x"},{"key":"S1121189X00004711_ref055","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.182.1.37"},{"key":"S1121189X00004711_ref015","unstructured":"Baldessarini R.J. , Tondo L. , Baethge C. & Bratti I.M. (in press). Effects of treatment latency on response to maintenance treatment in manic-depressive disorders. Bipolar Disorders."},{"key":"S1121189X00004711_ref085","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0327(02)00359-2"},{"key":"S1121189X00004711_ref067","doi-asserted-by":"publisher","DOI":"10.1097\/00005053-199304000-00005"},{"key":"S1121189X00004711_ref013","unstructured":"Baldessarini R.J. , Salvatore P. , Khalsa H.K. , Gonz\u00e1lez-Pinto A. , Baethge C. & Tohen M. (2004b). Early morbidity in first-episode bipolar I disorder patients treated by community standards (Abstract, poster). In Proceedings of American College of Neuropsychopharmacology (ACNP) Annual Meeting, San Juan (PR), December."},{"key":"S1121189X00004711_ref094","doi-asserted-by":"publisher","DOI":"10.1185\/030079906X104632"},{"key":"S1121189X00004711_ref012","first-page":"13","article-title":"Course and morbidity in bipolar disorder: New insights","volume":"10","author":"Baldessarini","year":"2004","journal-title":"Italian Journal of Psychopathology"},{"key":"S1121189X00004711_ref088","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/18.2.185"},{"key":"S1121189X00004711_ref029","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1176\/ajp.147.12.1627","article-title":"Outcome of patients with chronic affective disorder: A five-year follow-up","volume":"147","author":"Coryell","year":"1990","journal-title":"American Journal of Psychiatry"},{"key":"S1121189X00004711_ref017","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0327(00)00247-0"},{"key":"S1121189X00004711_ref037","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2004.12.006"},{"key":"S1121189X00004711_ref077","first-page":"349","volume-title":"Bipolar Disorder: One Hundred Years After Manic-Depressive Insanity","author":"Maj","year":"2001"},{"key":"S1121189X00004711_ref092","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v66n1006"},{"key":"S1121189X00004711_ref003","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2006.02.018"},{"key":"S1121189X00004711_ref104","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/18.2.273"},{"key":"S1121189X00004711_ref008","unstructured":"Baethge C. , Baldessarini R.J. , Hennen J. , Salvatore P. , Khalsa H.K. & Tohen M. (2006). Timing and substance-choice in early bipolar-I disorder: cannabis versus alcohol use selectively precede mania versus depression (Abstract\/Poster). In Proceedings of APA American Psychiatric Association Annual Meeting, Toronto (CA), May."},{"key":"S1121189X00004711_ref006","doi-asserted-by":"publisher","DOI":"10.1177\/070674370304800704"},{"key":"S1121189X00004711_ref098","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0327(02)00100-3"},{"key":"S1121189X00004711_ref118","doi-asserted-by":"publisher","DOI":"10.1007\/BF02238951"},{"key":"S1121189X00004711_ref063","doi-asserted-by":"publisher","DOI":"10.1097\/00005053-199505000-00008"},{"key":"S1121189X00004711_ref007","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.162.5.1008"},{"key":"S1121189X00004711_ref042","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.161.1.163"},{"key":"S1121189X00004711_ref113","unstructured":"Tondo L. , Lepri B. & Baldessarini R.J. (in review). Suicidal risks among 2826 major affective disorder patients. Acta Psychiatrica Scandinavica."},{"key":"S1121189X00004711_ref016","unstructured":"Baldessarini R.J. , Salvatore P. , Gonzalez-Pinto A. , Khalsa H.K. & Tohen M. (in preparation). Cycle progression in first-episode bipolar I manic-depressive patients."},{"key":"S1121189X00004711_ref089","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0447.1985.tb10510.x"},{"key":"S1121189X00004711_ref019","doi-asserted-by":"publisher","DOI":"10.1007\/BF00380941"},{"key":"S1121189X00004711_ref034","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v67n1106"},{"key":"S1121189X00004711_ref065","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1986.03370220100035"},{"key":"S1121189X00004711_ref005","doi-asserted-by":"publisher","DOI":"10.1007\/s00406-003-0437-2"},{"key":"S1121189X00004711_ref074","doi-asserted-by":"publisher","DOI":"10.1007\/BF00573638"},{"key":"S1121189X00004711_ref059","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-9964(99)00110-3"},{"key":"S1121189X00004711_ref030","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1176\/ajp.150.5.720","article-title":"The enduring psychosocial consequences of mania and depression","volume":"150","author":"Coryell","year":"1993","journal-title":"American Journal of Psychiatry"},{"key":"S1121189X00004711_ref083","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2006.03.013"},{"key":"S1121189X00004711_ref053","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1990.01810190065009"},{"key":"S1121189X00004711_ref004","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(00)00909-4"},{"key":"S1121189X00004711_ref105","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1176\/ajp.149.11.1580","article-title":"Prediction of outcome in mania: mood-congruent vs. -incongruent psychotic features","volume":"149","author":"Tohen","year":"1992","journal-title":"American Journal of Psychiatry"},{"key":"S1121189X00004711_ref002","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0327(00)00203-2"},{"key":"S1121189X00004711_ref054","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.0806e06"},{"key":"S1121189X00004711_ref069","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a009827"},{"key":"S1121189X00004711_ref040","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.178.41.s191"},{"key":"S1121189X00004711_ref031","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0327(94)00091-M"},{"key":"S1121189X00004711_ref039","doi-asserted-by":"publisher","DOI":"10.1016\/S0010-440X(00)80012-7"},{"key":"S1121189X00004711_ref010","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.57.5.490"},{"key":"S1121189X00004711_ref001","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1819.2006.01531.x"},{"key":"S1121189X00004711_ref106","doi-asserted-by":"publisher","DOI":"10.3928\/0048-5713-19960702-07"},{"key":"S1121189X00004711_ref066","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1987.01800180050009"},{"key":"S1121189X00004711_ref102","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0327(90)90012-W"},{"key":"S1121189X00004711_ref036","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1176\/ajp.146.11.1456","article-title":"The role of social relationships in the course of first-episode schizophrenia and affective psychosis","volume":"146","author":"Erickson","year":"1989","journal-title":"American Journal of Psychiatry"},{"key":"S1121189X00004711_ref023","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.178.5.420"},{"key":"S1121189X00004711_ref062","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.1206e17"},{"key":"S1121189X00004711_ref114","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0327(00)00163-4"},{"key":"S1121189X00004711_ref115","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1980.01780220017001"},{"key":"S1121189X00004711_ref116","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1980.01780300047005"},{"key":"S1121189X00004711_ref117","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0447.1999.tb07208.x"},{"key":"S1121189X00004711_ref119","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.161.5.615"},{"key":"S1121189X00004711_ref120","doi-asserted-by":"publisher","DOI":"10.1016\/0010-440X(89)90063-1"},{"key":"S1121189X00004711_ref121","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0447.1994.tb01495.x"},{"key":"S1121189X00004711_ref122","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1979.01780080009002"},{"key":"S1121189X00004711_ref011","doi-asserted-by":"publisher","DOI":"10.1080\/10673220216208"},{"key":"S1121189X00004711_ref075","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291700032797"},{"key":"S1121189X00004711_ref025","doi-asserted-by":"publisher","DOI":"10.1097\/01.psy.0000237316.09601.88"},{"key":"S1121189X00004711_ref018","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1176\/ajp.145.6.695","article-title":"Refining the diagnosis of schizophreniform disorder","volume":"145","author":"Beiser","year":"1988","journal-title":"American Journal of Psychiatry"},{"key":"S1121189X00004711_ref070","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.185.5.372"},{"key":"S1121189X00004711_ref047","volume-title":"Manic-Depressive Illness","author":"Goodwin","year":"1990"},{"key":"S1121189X00004711_ref022","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291700035285"},{"key":"S1121189X00004711_ref091","unstructured":"Salvatore P. , Imaz H. & Baldessarini R.J. (in preparation). Cycle progression in bipolar manic-depressive disorders: a critical review."},{"key":"S1121189X00004711_ref068","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.172.1.23"},{"key":"S1121189X00004711_ref100","doi-asserted-by":"publisher","DOI":"10.1002\/0471234311.ch17"},{"key":"S1121189X00004711_ref049","volume-title":"Bonn Scale for Assessment of Basic Symptoms","author":"Gross","year":"1987"},{"key":"S1121189X00004711_ref045","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1176\/ajp.152.3.379","article-title":"Course and outcome in bipolar affective disorder: A longitudinal follow-up study","volume":"152","author":"Goldberg","year":"1995","journal-title":"American Journal of Psychiatry"},{"key":"S1121189X00004711_ref050","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-9964(96)00078-3"}],"container-title":["Epidemiologia e Psichiatria Sociale"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S1121189X00004711","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T22:19:22Z","timestamp":1556749162000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S1121189X00004711\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,6]]},"references-count":122,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2007,6]]}},"alternative-id":["S1121189X00004711"],"URL":"https:\/\/doi.org\/10.1017\/s1121189x00004711","relation":{},"ISSN":["1121-189X","2038-1816"],"issn-type":[{"value":"1121-189X","type":"print"},{"value":"2038-1816","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,6]]}}}