{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T02:31:49Z","timestamp":1790908309335,"version":"4.1.0"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2001,7,1]],"date-time":"2001-07-01T00:00:00Z","timestamp":993945600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2001,7,1]],"date-time":"2001-07-01T00:00:00Z","timestamp":993945600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Psychiatry"],"published-print":{"date-parts":[[2001,7,1]]},"DOI":"10.1038\/sj.mp.4000906","type":"journal-article","created":{"date-parts":[[2002,9,19]],"date-time":"2002-09-19T21:18:58Z","timestamp":1032470338000},"page":"363-366","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Proposed endophenotypes of dysthymia: evolutionary, clinical and pharmacogenomic considerations"],"prefix":"10.1038","volume":"6","author":[{"given":"A B","family":"Niculescu III","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H S","family":"Akiskal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2001,7,9]]},"reference":[{"key":"BF4000906_CR1","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1111\/j.2044-8341.1998.tb00999.x","volume":"71","author":"DR Wilson","year":"1998","unstructured":"Wilson DR . Evolutionary epidemiology and manic depression Br J Med Psychol 1998 71: 375\u2013395","journal-title":"Br J Med Psychol"},{"key":"BF4000906_CR2","first-page":"pp\u2009736","volume-title":"New Oxford Textbook of Psychiatry","author":"HS Akiskal","year":"2000","unstructured":"Akiskal HS . Dysthymia, cyclothymia and related chronic subthreshold mood disorders. In: Gelder M, Lopez-Ibor J, Andreasen N (eds) New Oxford Textbook of Psychiatry Oxford University Press: London 2000 pp\u2009736\u2013749"},{"key":"BF4000906_CR3","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1176\/ajp.145.7.815","volume":"145","author":"MM Weissman","year":"1988","unstructured":"Weissman MM, Leaf PJ, Bruce ML, Florio L . The epidemiology of dysthymia in five communities: rates, risks, comorbidity, and treatment Am J Psychiatry 1988 145: 815\u2013819","journal-title":"Am J Psychiatry"},{"key":"BF4000906_CR4","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1176\/ajp.140.1.11","volume":"140","author":"HS Akiskal","year":"1983","unstructured":"Akiskal HS . Dysthymic disorder: psychopathology of proposed chronic depressive subtypes Am J Psychiatry 1983 140: 11\u201320","journal-title":"Am J Psychiatry"},{"key":"BF4000906_CR5","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/S0165-0327(98)00163-3","volume":"52","author":"N Brunello","year":"1999","unstructured":"Brunello N, Akiskal H, Boyer P, Gessa GL, Howland RH, Langer SZ et al. Dysthymia: clinical picture, extent of overlap with chronic fatigue syndrome, neuropharmacological considerations, and new therapeutic vistas J Affect Disord 1999 52: 275\u2013290","journal-title":"J Affect Disord"},{"key":"BF4000906_CR6","doi-asserted-by":"publisher","first-page":"117s","DOI":"10.1016\/0924-9338(96)85185-6","volume":"11 (suppl 3)","author":"HS Akiskal","year":"1996","unstructured":"Akiskal HS . Dysthymia as a temperamental variant of affective disorder Eur Psychiatry 1996 11 (suppl 3): 117s\u2013122s","journal-title":"Eur Psychiatry"},{"key":"BF4000906_CR7","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/S0165-0327(98)00152-9","volume":"51","author":"HS Akiskal","year":"1998","unstructured":"Akiskal HS, Placidi GF, Signoretta S, Liguori A, Gervasi R, Maremmani I et al. TEMPS-I: Delineating the most discriminant traits of cyclothymic, depressive, irritable and hyperthymic temperaments in a nonpatient population J Affect Disord 1998 51: 7\u201319","journal-title":"J Affect Disord"},{"key":"BF4000906_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0165-0327(97)00122-5","volume":"47","author":"GF Placidi","year":"1998","unstructured":"Placidi GF, Signoretta S, Liguori A, Gervasi R, Maremmani I, Akiskal HS . The Semi-Structured Affective Temperament Interview (TEMPS-I): reliability and psychometric properties in 1010 14\u201326 year students J Affect Disord 1998 47: 1\u201310","journal-title":"J Affect Disord"},{"key":"BF4000906_CR9","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1001\/archpsyc.57.1.14","volume":"57","author":"RM Nesse","year":"2000","unstructured":"Nesse RM . Is depression an adaptation? Arch Gen Psychiatry 2000 57: 14\u201320","journal-title":"Arch Gen Psychiatry"},{"key":"BF4000906_CR10","unstructured":"Niculescu AB, HS Akiskal . Sex hormones, Darwinism and depression Arch Gen Psychiatry (in press)"},{"key":"BF4000906_CR11","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/0165-0327(92)90020-7","volume":"24","author":"JC Markowitz","year":"1992","unstructured":"Markowitz JC, Moran ME, Kocsis JH, Frances AJ . Prevalence and comorbidity of dysthymic disorder among psychiatric outpatients J Affect Disord 1992 24: 63\u201371","journal-title":"J Affect Disord"},{"key":"BF4000906_CR12","doi-asserted-by":"publisher","first-page":"508","DOI":"10.4088\/JCP.v60n0802","volume":"60","author":"RF Haykal","year":"1999","unstructured":"Haykal RF, HS Akiskal . The long-term outcome of dysthymia in private practice: clinical features, temperament, and the art of management J Clin Psychiatry 1999 60: 508\u2013518","journal-title":"J Clin Psychiatry"},{"key":"BF4000906_CR13","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/S0165-0327(84)80007-5","volume":"6","author":"HS Akiskal","year":"1984","unstructured":"Akiskal HS, Lemmi H, Dickson H, King D, Yerevanian B, Van Valkenburg C . Chronic depressions Part 2. Sleep EEG differentiation of primary dysthymic disorder from anxious depressions J Affect Disord 1984 6: 287\u2013295","journal-title":"J Affect Disord"},{"key":"BF4000906_CR14","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1046\/j.1525-1381.1999.09423.x","volume":"111","author":"PW Gold","year":"1999","unstructured":"Gold PW, Chrousos GP . The endocrinology of melancholic and atypical depression: relation to neurocircuitry and somatic consequences Proc Assoc Am Physicians 1999 111: 22\u201334","journal-title":"Proc Assoc Am Physicians"},{"key":"BF4000906_CR15","doi-asserted-by":"publisher","first-page":"1614","DOI":"10.1016\/S0006-3223(99)00212-7","volume":"46","author":"L Tebartz van Elst","year":"1999","unstructured":"Tebartz van Elst L, Woermann FG, Lemieux L, Trimble MR . Amygdala enlargement in dysthymia\u2014a volumetric study of patients with temporal lobe epilepsy Biol Psychiatry 1999 46: 1614\u20131623","journal-title":"Biol Psychiatry"},{"key":"BF4000906_CR16","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1126\/science.182.4107.20","volume":"182","author":"HS Akiskal","year":"1973","unstructured":"Akiskal HS, McKinney WT . Depressive disorders: toward a unified hypothesis Science 1973 182: 20\u201329","journal-title":"Science"},{"key":"BF4000906_CR17","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1016\/S0006-3223(00)00998-7","volume":"48","author":"J Kaufman","year":"2000","unstructured":"Kaufman J, Plotsky PM, Nemeroff CB, Charney DS . Effects of early adverse experiences on brain structure and function: clinical implications Biol Psychiatry 2000 48: 778\u2013790","journal-title":"Biol Psychiatry"},{"key":"BF4000906_CR18","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1046\/j.1440-1819.2000.00742.x","volume":"54","author":"F Benazzi","year":"2000","unstructured":"Benazzi F . Characteristics of bipolar II patients with interpersonal rejection sensitivity Psychiatry Clin Neurosci 2000 54: 499\u2013501","journal-title":"Psychiatry Clin Neurosci"},{"key":"BF4000906_CR19","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/S0193-953X(18)30935-3","volume":"4","author":"HS Akiskal","year":"1981","unstructured":"Akiskal HS . Subaffective disorders: dysthymic, cyclothymic, and bipolar II disorders in the \u2018borderline\u2019 realm Psychiatr Clin North Am 1981 4: 25\u201346","journal-title":"Psychiatr Clin North Am"},{"key":"BF4000906_CR20","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1176\/ajp.153.7.900","volume":"153","author":"LP Riso","year":"1996","unstructured":"Riso LP, Klein DN, Ferro T, Kasch KL, Pepper CM, Schwartz JE et al. Understanding the co-morbidity between early-onset dysthymia and cluster B personality disorders: a family study Am J Psychiatry 1996 153: 900\u2013906","journal-title":"Am J Psychiatry"},{"key":"BF4000906_CR21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0165-0327(99)00158-5","volume":"60","author":"SG Kornstein","year":"2000","unstructured":"Kornstein SG, Schatzberg AF, Thase ME, Yonkers KA, McCollough JP, Keitner GI et al. Gender differences in chronic major and double depression J Affect Disord 2000 60: 1\u201311","journal-title":"J Affect Disord"},{"key":"BF4000906_CR22","doi-asserted-by":"publisher","first-page":"1445","DOI":"10.1176\/appi.ajp.157.9.1445","volume":"157","author":"SG Kornstein","year":"2000","unstructured":"Kornstein SG, Schatzberg AF, Thase ME, Yonkers KA, McCollough JP, Keitner GI et al. Gender differences in treatment response to sertraline versus imipramine in chronic depression Am J Psychiatry 2000 157: 1445\u20131452","journal-title":"Am J Psychiatry"},{"key":"BF4000906_CR23","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/S0010-440X(98)90080-3","volume":"39","author":"G Perugi","year":"1998","unstructured":"Perugi G, Akiskal HS, Lattanzi L, Cecconi D, Mastrocinque C, Patronelli A et al. The high prevalence of soft bipolar (II) features in atypical depression Compr Psychiatry 1998 39: 63\u201371","journal-title":"Compr Psychiatry"},{"key":"BF4000906_CR24","first-page":"4140","volume":"83","author":"J Licino","year":"1998","unstructured":"Licino J, Negrao AB, Mantzoros C, Kaklamani V, Wong ML, Bongiorno PB et al. Sex differences in circulating human leptin pulse amplitude: clinical implications J Clin Endocrinol Metab 1998 83: 4140\u20134147","journal-title":"J Clin Endocrinol Metab"},{"key":"BF4000906_CR25","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/0165-0327(81)90043-4","volume":"3","author":"TL Rosenthal","year":"1981","unstructured":"Rosenthal TL, Akiskal HS, Scott-Strauss A, Rosenthal RH, David M . Familial and developmental factors in characterological depressions J Affective Disord 1981 3: 183\u2013192","journal-title":"J Affective Disord"},{"key":"BF4000906_CR26","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/S0306-4530(00)00044-5","volume":"26","author":"M Altemus","year":"2001","unstructured":"Altemus M, Dale JK, Michelson D, Demitrack MA, Gold PW, Straus SE . Abnormalities in response to vasopressin infusion in chronic fatigue syndrome Psychoneuroendocrinology 2001 26: 175\u2013188","journal-title":"Psychoneuroendocrinology"},{"key":"BF4000906_CR27","doi-asserted-by":"publisher","first-page":"1706","DOI":"10.1001\/archinte.160.11.1706","volume":"160","author":"AB Niculescu","year":"2000","unstructured":"Niculescu AB . Will to live, suicide and euthanasia Arch Int Med 2000 160: 1706","journal-title":"Arch Int Med"},{"key":"BF4000906_CR28","first-page":"559","volume":"S3","author":"Y Lecrubier","year":"1994","unstructured":"Lecrubier Y, Weiller E . Neurasthenia and thymasthenia Encephale 1994 S3: 559\u2013562","journal-title":"Encephale"},{"key":"BF4000906_CR29","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/S0165-0327(99)00056-7","volume":"56","author":"A Serretti","year":"1999","unstructured":"Serretti A, Jori MC, Casadei G, Ravizza L, Smeraldi E, HS Akiskal . Delineating psychopathologic clusters within dysthymia: a study of 512 outpatients without major depression J Affect Disord 1999 56: 17\u201325","journal-title":"J Affect Disord"},{"key":"BF4000906_CR30","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1001\/archpsyc.1980.01780200055006","volume":"37","author":"HS Akiskal","year":"1980","unstructured":"Akiskal HS, Rosenthal TL, Haykal RF, Lemmi H, Rosenthal RH, Scott-Strauss A . Characterological depressions. Clinical and sleep EEG findings separating \u2018subaffective dysthymias\u2019 from \u2018character spectrum disorders\u2019 Arch Gen Psychiatry 1980 37: 777\u2013783","journal-title":"Arch Gen Psychiatry"},{"key":"BF4000906_CR31","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1038\/sj.mp.4000589","volume":"5","author":"L Pani","year":"2000","unstructured":"Pani L, Porcella A, Gessa GL . The role of stress in the pathophysiology of the dopaminergic system Mol Psychiatry 2000 5: 14\u201321","journal-title":"Mol Psychiatry"},{"key":"BF4000906_CR32","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1001\/archpsyc.1994.03950050025003","volume":"51","author":"M Kovacs","year":"1994","unstructured":"Kovacs M, Akiskal HS, Gatsonis C, Parrone PL . Childhood-onset dysthymic disorder: clinical features and prospective naturalistic outcome Arch Gen Psychiatry 1994 51: 365\u2013374","journal-title":"Arch Gen Psychiatry"},{"key":"BF4000906_CR33","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/S0165-0327(96)00103-6","volume":"43","author":"Y Lecrubier","year":"1997","unstructured":"Lecrubier Y, Boyer P, Turjanski S, Rein W . Amisulpride versus imipramine and placebo in dysthymia and major depression J Affect Disord 1997 43: 95\u2013103","journal-title":"J Affect Disord"},{"key":"BF4000906_CR34","doi-asserted-by":"publisher","first-page":"634","DOI":"10.1016\/0278-5846(95)00108-8","volume":"19","author":"AV Ravindran","year":"1995","unstructured":"Ravindran AV, Griffiths J, Waddell C, Anisman H . Stressful life events and coping styles in relation to dysthymia and major depressive disorder: variations associated with alleviation of symptoms following pharmacotherapy Prog Neuro-Psychopharmacol Biol Psychiatry 1995 19: 634\u2013653","journal-title":"Prog Neuro-Psychopharmacol Biol Psychiatry"},{"key":"BF4000906_CR35","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1038\/sj.mp.4000436","volume":"4","author":"H Anisman","year":"1999","unstructured":"Anisman H, Ravindran AV, Griffiths J, Merali Z . Endocrine and cytokine correlates of major depression and dysthymia with typical or atypical features Mol Psychiatry 1999 4: 182\u2013188","journal-title":"Mol Psychiatry"},{"key":"BF4000906_CR36","doi-asserted-by":"publisher","first-page":"1649","DOI":"10.1016\/S0006-3223(99)00211-5","volume":"46","author":"H Anisman","year":"1999","unstructured":"Anisman H, Ravindran AV, Griffiths J, Merali Z . Interleukin-1 beta production in dysthymia before and after pharmacotherapy Biol Psychiatry 1999 46: 1649\u20131655","journal-title":"Biol Psychiatry"},{"key":"BF4000906_CR37","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/S0165-0327(99)00102-0","volume":"58","author":"KC Moerk","year":"2000","unstructured":"Moerk KC, DN Klein . The development of major depressive episodes during the course of dysthymic and episodic major depressive disorders: a retrospective examination of life events J Affect Disord 2000 58: 117\u2013123","journal-title":"J Affect Disord"},{"key":"BF4000906_CR38","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1055\/s-2000-7967","volume":"33","author":"LL Judd","year":"2000","unstructured":"Judd LL, HS Akiskal . Delineating the longitudinal structure of depressive illness: beyond clinical subtypes and duration thresholds Pharmacopsychiatry 2000 33: 3\u20137","journal-title":"Pharmacopsychiatry"},{"key":"BF4000906_CR39","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1038\/sj.mp.4000697","volume":"5","author":"J Griffiths","year":"2000","unstructured":"Griffiths J, Ravindran AV, Merali Z, Anisman H . Dysthymia: a review of pharmacological and behavioral factors Mol Psychiatry 2000 5: 242\u2013261","journal-title":"Mol Psychiatry"},{"key":"BF4000906_CR40","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1001\/archpsyc.57.4.375","volume":"57","author":"LL Judd","year":"2000","unstructured":"Judd LL, Akiskal HS, Zeller PJ, Paulus M, Leon AC, Maser JD et al. Psychosocial disability during the long-term course of unipolar major depressive disorder Arch Gen Psychiatry 2000 57: 375\u2013380","journal-title":"Arch Gen Psychiatry"},{"key":"BF4000906_CR41","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1001\/archpsyc.1992.01820100032007","volume":"49","author":"KB Wells","year":"1992","unstructured":"Wells KB, Burnam MA, Rogers W, Hays R, Camp P . The course of depression in adult outpatients: results from the Medical Outcomes Study Arch Gen Psychiatry 1992 49: 788\u2013794","journal-title":"Arch Gen Psychiatry"},{"key":"BF4000906_CR42","first-page":"478","volume":"1","author":"HS Akiskal","year":"1996","unstructured":"Akiskal HS, Bolis CL, Cazzullo C, Costa e Silva JA, Gentil V, Lecrubier Y et al. Dysthymia in neurological disorders Mol Psychiatry 1996 1: 478\u2013491","journal-title":"Mol Psychiatry"},{"key":"BF4000906_CR43","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1016\/S0140-6736(05)74028-9","volume":"355","author":"AB Niculescu","year":"2000","unstructured":"Niculescu AB . Prophylactic antidepressant treatment before patients are admitted Lancet 2000 355: 406\u2013407","journal-title":"Lancet"},{"key":"BF4000906_CR44","doi-asserted-by":"publisher","first-page":"821","DOI":"10.4088\/JCP.v61n1103","volume":"61","author":"AV Ravindran","year":"2000","unstructured":"Ravindran AV, Guelfi JD, Lane RM, Cassano GB . Treatment of dysthymia with sertraline: a double-blind, placebo-controlled trial in dysthymic patients without major depression J Clin Psychiatry 2000 61: 821\u2013827","journal-title":"J Clin Psychiatry"},{"key":"BF4000906_CR45","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1152\/physiolgenomics.2000.4.1.83","volume":"4","author":"AB Niculescu","year":"2000","unstructured":"Niculescu AB, Segal D, Kuczenski R, Barrett T, Hauger R, JR Kelsoe . Identifying a series of candidate genes for mania and psychosis: a convergent functional genomics approach Physiol Genomics 2000 4: 83\u201391","journal-title":"Physiol Genomics"},{"key":"BF4000906_CR46","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1016\/S0006-3223(00)00929-X","volume":"48","author":"HK Manji","year":"2000","unstructured":"Manji HK, Lenox RH . Signaling: cellular insights into the pathophysiology of bipolar disorder Biol Psychiatry 2000 48: 518\u2013530","journal-title":"Biol Psychiatry"}],"container-title":["Molecular Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/4000906.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/4000906","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/4000906.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T03:47:29Z","timestamp":1648784849000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/4000906"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,7,1]]},"references-count":46,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2001,7,1]]}},"alternative-id":["BF4000906"],"URL":"https:\/\/doi.org\/10.1038\/sj.mp.4000906","relation":{},"ISSN":["1359-4184","1476-5578"],"issn-type":[{"value":"1359-4184","type":"print"},{"value":"1476-5578","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,7,1]]},"assertion":[{"value":"30 January 2001","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 February 2001","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 February 2001","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 July 2001","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}