{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T23:34:53Z","timestamp":1774481693769,"version":"3.50.1"},"reference-count":49,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,23]],"date-time":"2023-12-23T00:00:00Z","timestamp":1703289600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>(1) Background: Bipolar disorder (BD) is divided into type I (BD-I) and type II (BD-II). Polarity at onset (PO) is a proposal to specify the clinical course of BD, based on the type of the first episode at disorder onset\u2014depressive (D-PO) or manic (M-PO). At the same time, affective temperaments represent preexisting variants of the spectrum of affective disorders. Our objectives were to investigate the hypothesis that temperament may exert an influence on PO, and that this factor can serve as an indicator of the forthcoming course of the disorder, carrying significant therapeutic implications. (2) Methods: We included 191 patients with BD and examined clinical variables and temperament; the latter was assessed using the short version of the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego\u2014Auto-questionnaire (TEMPS-A-39-SV). We tested the associations between these variables and PO using standard univariate\/bivariate methods followed by multivariate logistic regression models. (3) Results: 52.9% of the sample had D-PO and 47.1% had M-PO. D-PO and M-PO patients scored higher for dysthymic and hyperthymic temperaments, respectively (p &lt; 0.001). Also, they differed in BD subtypes, age at first affective episode, illness duration, number of depressive episodes, seasonality, suicide risk, substance use, lithium, and benzodiazepine use (p &lt; 0.05). Only BD-II and age at first depressive episode were predictors of D-PO, whereas BD-I, age at first manic\/hypomanic episode, and hyperthymic temperament were predictors of M-PO (p &lt; 0.01). (4) Conclusions: Our findings point to the importance of carefully assessing temperament and PO in patients with BD, to better predict the clinical course and tailor therapeutic interventions to individual patients\u2019 needs.<\/jats:p>","DOI":"10.3390\/brainsci14010017","type":"journal-article","created":{"date-parts":[[2023,12,24]],"date-time":"2023-12-24T20:42:30Z","timestamp":1703450550000},"page":"17","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["What Came First, Mania or Depression? Polarity at Onset in Bipolar I and II: Temperament and Clinical Course"],"prefix":"10.3390","volume":"14","author":[{"given":"Delfina","family":"Janiri","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Section of Psychiatry, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessio","family":"Simonetti","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Section of Psychiatry, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenzo","family":"Moccia","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Section of Psychiatry, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele","family":"Hirsch","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Section of Psychiatry, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Montanari","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Section of Psychiatry, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3007-8162","authenticated-orcid":false,"given":"Marianna","family":"Mazza","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Section of Psychiatry, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7457-0426","authenticated-orcid":false,"given":"Marco","family":"Di Nicola","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Section of Psychiatry, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0281-6324","authenticated-orcid":false,"given":"Georgios D.","family":"Kotzalidis","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Section of Psychiatry, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9767-8752","authenticated-orcid":false,"given":"Gabriele","family":"Sani","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Section of Psychiatry, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s40345-022-00268-2","article-title":"Differences between Bipolar Disorder Types 1 and 2 Support the DSM Two-Syndrome Concept","volume":"10","author":"Tondo","year":"2022","journal-title":"Int. J. Bipolar. Disord."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.jad.2020.06.041","article-title":"Person-Based Similarity in Brain Structure and Functional Connectivity in Bipolar Disorder","volume":"276","author":"Doucet","year":"2020","journal-title":"J. Affect. Disord."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1001\/jamapsychiatry.2018.2467","article-title":"Mapping the Heterogeneous Phenotype of Schizophrenia and Bipolar Disorder Using Normative Models","volume":"75","author":"Wolfers","year":"2018","journal-title":"JAMA Psychiatry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1176\/appi.ajp.2017.17090972","article-title":"Early Intervention in Bipolar Disorder","volume":"175","author":"Vieta","year":"2018","journal-title":"Am. J. Psychiatry"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1111\/j.1399-5618.2008.00654.x","article-title":"Polarity at Illness Onset in Bipolar I Disorder and Clinical Course of Illness","volume":"11","author":"Forty","year":"2009","journal-title":"Bipolar Disord."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0010-440X(00)90125-1","article-title":"Polarity of the First Episode, Clinical Characteristics, and Course of Manic Depressive Illness: A Systematic Retrospective Investigation of 320 Bipolar I Patients","volume":"41","author":"Perugi","year":"2000","journal-title":"Compr. Psychiatry"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.biopsych.2005.07.029","article-title":"Revisiting Depressive-Prone Bipolar Disorder: Polarity of Initial Mood Episode and Disease Course among Bipolar I Systematic Treatment Enhancement Program for Bipolar Disorder Participants","volume":"58","author":"Perlis","year":"2005","journal-title":"Biol. Psychiatry"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.comppsych.2006.03.009","article-title":"Clinical Correlates of First-Episode Polarity in Bipolar Disorder","volume":"47","author":"Daban","year":"2006","journal-title":"Compr. Psychiatry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1176\/ajp.2006.163.10.1754","article-title":"Familiality of Polarity at Illness Onset in Bipolar Affective Disorder","volume":"163","author":"Kassem","year":"2006","journal-title":"Am. J. Psychiatry"},{"key":"ref_10","first-page":"5","article-title":"Temperament and Mood Disorders","volume":"16","author":"Akiskal","year":"2000","journal-title":"Harv. Ment. Health Lett."},{"key":"ref_11","first-page":"1","article-title":"Personality Factors in Affective Disorders: Historical Developments and Current Issues with Special Reference to the Concepts of Temperament and Character","volume":"51","author":"Zerssen","year":"1998","journal-title":"J. Affect. Disord."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"632A","DOI":"10.1097\/00002826-199201001-00327","article-title":"The Distinctive Mixed States of Bipolar I, II, and III","volume":"15 Pt A","author":"Akiskal","year":"1992","journal-title":"Clin. Neuropharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1007\/BF02189532","article-title":"The Manic-Depressive Mixed State: Familial, Temperamental and Psychopathologic Characteristics in 108 Female Inpatients","volume":"240","author":"Placidi","year":"1991","journal-title":"Eur. Arch Psychiatry Clin. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S0165-0327(98)00113-X","article-title":"Gender, Temperament, and the Clinical Picture in Dysphoric Mixed Mania: Findings from a French National Study (EPIMAN)","volume":"50","author":"Akiskal","year":"1998","journal-title":"J. Affect. Disord."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S0165-1781(01)00232-3","article-title":"The Contrasting Influence of Depressive Hyperthymic Temperaments on Psychometrically Derived Manic Subtypes","volume":"101","author":"Perugi","year":"2001","journal-title":"Psychiatry Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.jad.2010.08.020","article-title":"Correlates of First-Episode Polarity in a French Cohort of 1089 Bipolar i Disorder Patients: Role of Temperaments and Triggering Events","volume":"129","author":"Azorin","year":"2011","journal-title":"J. Affect. Disord."},{"key":"ref_17","unstructured":"First, M.B., Williams, J.B.W., Karg, R.S., and Spitzer, R.L. (2016). Structured Clinical Interview for DSM-5 Disorders, Clinician Version (SCID-5-CV), American Psychiatric Association."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0022-3956(75)90026-6","article-title":"\u201cMini-Mental State\u201d. A Practical Method for Grading the Cognitive State of Patients for the Clinician","volume":"12","author":"Folstein","year":"1975","journal-title":"J. Psychiatr. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.jad.2022.01.001","article-title":"Substance Use Disorders in Bipolar Disorders: Clinical Correlates and Treatment Response to Mood Stabilizers","volume":"300","author":"Menculini","year":"2022","journal-title":"J. Affect. Disord."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s12991-022-00428-9","article-title":"What Influences Psychological Functioning in Patients with Mood Disorders? The Role of Clinical, Sociodemographic, and Temperamental Characteristics in a Naturalistic Study","volume":"21","author":"Sampogna","year":"2022","journal-title":"Ann. Gen. Psychiatry"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1111\/bdi.12857","article-title":"Predominant Polarity and Hippocampal Subfield Volumes in Bipolar Disorders","volume":"22","author":"Janiri","year":"2020","journal-title":"Bipolar Disord."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.jad.2009.02.025","article-title":"The Italian Version of the Validated Short TEMPS-A: The Temperament Evaluation of Memphis, Pisa, Paris and San Diego","volume":"120","author":"Preti","year":"2010","journal-title":"J. Affect. Disord."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.jad.2017.01.023","article-title":"Measuring Affective Temperaments: A Systematic Review of Validation Studies of the Temperament Evaluation in Memphis Pisa and San Diego (TEMPS) Instruments","volume":"212","author":"Elias","year":"2017","journal-title":"J. Affect. Disord."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.jad.2004.12.001","article-title":"TEMPS-A: Progress towards Validation of a Self-Rated Clinical Version of the Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego Autoquestionnaire","volume":"85","author":"Akiskal","year":"2005","journal-title":"J. Affect. Disord."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"100501","DOI":"10.1016\/j.jadr.2023.100501","article-title":"Psychometric Properties of the Short Version of Temperament Evaluation of Memphis, Pisa, Paris, and San Diego\u2014Autoquestionnaire (TEMPS-A): Persian Version","volume":"12","author":"Nabizadehchianeh","year":"2023","journal-title":"J. Affect. Disord. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Mazza, M., Caroppo, E., Berardis, D.D., Marano, G., Avallone, C., Kotzalidis, G.D., Janiri, D., Moccia, L., Simonetti, A., and Conte, E. (2021). Psychosis in Women: Time for Personalized Treatment. J. Pers. Med., 11.","DOI":"10.3390\/jpm11121279"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.jad.2019.02.053","article-title":"Predominant Polarity in Bipolar Disorder Patients: The COPE Bipolar Sample","volume":"250","author":"Sentissi","year":"2019","journal-title":"J. Affect. Disord."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.jad.2015.04.037","article-title":"Predominant Polarity in Bipolar Disorders: Further Evidence for the Role of Affective Temperaments","volume":"182","author":"Azorin","year":"2015","journal-title":"J. Affect. Disord."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.jad.2006.01.032","article-title":"Clinical and Therapeutic Implications of Predominant Polarity in Bipolar Disorder","volume":"93","author":"Colom","year":"2006","journal-title":"J. Affect. Disord."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/S0165-0327(98)00219-5","article-title":"Temperament in Bipolar Illness: Impact on Prognosis","volume":"56","author":"Henry","year":"1999","journal-title":"J. Affect. Disord."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1111\/acps.13569","article-title":"Familial Traits of Bipolar Disorder: A Systematic Review and Meta-Analysis","volume":"148","author":"Scott","year":"2023","journal-title":"Acta Psychiatr. Scand."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1097\/00004703-200506000-00010","article-title":"Behavioral Genetics and Child Temperament","volume":"26","author":"Saudino","year":"2005","journal-title":"J. Dev. Behav. Pediatr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1192\/bjp.2021.102","article-title":"Characterisation of Age and Polarity at Onset in Bipolar Disorder","volume":"219","author":"Kalman","year":"2021","journal-title":"Br. J. Psychiatry"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Moccia, L., Janiri, D., Giuseppin, G., Agrifoglio, B., Monti, L., Mazza, M., Caroppo, E., Fiorillo, A., Sani, G., and Nicola, M.D. (2021). Reduced Hedonic Tone and Emotion Dysregulation Predict Depressive Symptoms Severity during the COVID-19 Outbreak: An Observational Study on the Italian General Population. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph18010255"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1111\/acps.12179","article-title":"Clinical Implications of Predominant Polarity and the Polarity Index in Bipolar Disorder: A Naturalistic Study","volume":"129","author":"Popovic","year":"2014","journal-title":"Acta Psychiatr. Scand."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s40345-023-00304-9","article-title":"Differential Characteristics of Bipolar I and II Disorders: A Retrospective, Cross-Sectional Evaluation of Clinical Features, Illness Course, and Response to Treatment","volume":"11","author":"Brancati","year":"2023","journal-title":"Int. J. Bipolar. Disord."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1055\/s-2007-1019628","article-title":"Course of the Manic-Depressive Cycle and Changes Caused by Treatments","volume":"13","author":"Kukopulos","year":"1980","journal-title":"Pharmakopsychiatr. Neuropsychopharmakol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.jad.2016.11.043","article-title":"Onset Polarity in Bipolar Disorder: A Strong Association between First Depressive Episode and Suicide Attempts","volume":"209","author":"Cremaschi","year":"2017","journal-title":"J. Affect. Disord."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.eurpsy.2018.05.009","article-title":"Psychopathological Characteristics and Adverse Childhood Events Are Differentially Associated with Suicidal Ideation and Suicidal Acts in Mood Disorders","volume":"53","author":"Janiri","year":"2018","journal-title":"Eur. Psychiatry"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.jpsychires.2020.12.041","article-title":"Clinical Predictors of Recurrences in Bipolar Disorders Type 1 and 2: A FACE-BD Longitudinal Study","volume":"134","author":"Etain","year":"2021","journal-title":"J. Psychiatr. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1176\/appi.ajp.2012.12030401","article-title":"The Dutch Bipolar Offspring Study: 12-Year Follow-Up","volume":"170","author":"Mesman","year":"2013","journal-title":"Am. J. Psychiatry"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.jad.2007.01.027","article-title":"History of Illness Prior to a Diagnosis of Bipolar Disorder or Schizoaffective Disorder","volume":"103","author":"Berk","year":"2007","journal-title":"J. Affect. Disord."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.eurpsy.2008.07.006","article-title":"The Primacy of Mania: A Reconsideration of Mood Disorders","volume":"24","author":"Koukopoulos","year":"2009","journal-title":"Eur. Psychiatry"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.jad.2006.08.031","article-title":"Endogenous and Exogenous Cyclicity and Temperament in Bipolar Disorder: Review, New Data and Hypotheses","volume":"96","author":"Koukopoulos","year":"2006","journal-title":"J. Affect. Disord."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"339","DOI":"10.2174\/1570159X14666160708231216","article-title":"Neurobiological Evidence for the Primacy of Mania Hypothesis","volume":"15","author":"Kotzalidis","year":"2016","journal-title":"Curr. Neuropharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"402","DOI":"10.2174\/1570159X14666160621113432","article-title":"Athanasios Koukopoulos\u2019 Psychiatry: The Primacy of Mania and the Limits of Antidepressants","volume":"15","author":"Ghaemi","year":"2017","journal-title":"Curr. Neuropharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"247","DOI":"10.3389\/fpsyt.2020.00247","article-title":"Stabilization beyond Mood: Stabilizing Patients with Bipolar Disorder in the Various Phases of Life","volume":"11","author":"Simonetti","year":"2020","journal-title":"Front. Psychiatry"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1001\/jama.2023.18588","article-title":"Diagnosis and Treatment of Bipolar Disorder: A Review","volume":"330","author":"Nierenberg","year":"2023","journal-title":"JAMA"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1002\/phar.1260","article-title":"Intramuscular Aripiprazole in the Acute Management of Psychomotor Agitation","volume":"33","author":"Cuomo","year":"2013","journal-title":"Pharmacotherapy"}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/14\/1\/17\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:41:05Z","timestamp":1760132465000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/14\/1\/17"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,23]]},"references-count":49,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["brainsci14010017"],"URL":"https:\/\/doi.org\/10.3390\/brainsci14010017","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,23]]}}}