{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T22:20:12Z","timestamp":1793658012128,"version":"4.5.1"},"reference-count":75,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T00:00:00Z","timestamp":1657065600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Substance use disorder (SUD) is a common comorbidity in individuals with bipolar disorder (BD), and it is associated with a severe course of illness, making early identification of the risk factors for SUD in BD warranted. We aimed to identify, through machine-learning models, the factors associated with different types of SUD in BD. We recruited 508 individuals with BD from a specialized unit. Lifetime SUDs were defined according to the DSM criteria. Random forest (RF) models were trained to identify the presence of (i) any (SUD) in the total sample, (ii) alcohol use disorder (AUD) in the total sample, (iii) AUD co-occurrence with at least another SUD in the total sample (AUD+SUD), and (iv) any other SUD among BD patients with AUD. Relevant variables selected by the RFs were considered as independent variables in multiple logistic regressions to predict SUDs, adjusting for relevant covariates. AUD+SUD could be predicted in BD at an individual level with a sensitivity of 75% and a specificity of 75%. The presence of AUD+SUD was positively associated with having hypomania as the first affective episode (OR = 4.34 95% CI = 1.42\u201313.31), and the presence of hetero-aggressive behavior (OR = 3.15 95% CI = 1.48\u20136.74). Machine-learning models might be useful instruments to predict the risk of SUD in BD, but their efficacy is limited when considering socio-demographic or clinical factors alone.<\/jats:p>","DOI":"10.3390\/jcm11143935","type":"journal-article","created":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T09:41:10Z","timestamp":1657100470000},"page":"3935","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Machine Learning Prediction of Comorbid Substance Use Disorders among People with Bipolar Disorder"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5961-6032","authenticated-orcid":false,"given":"Vincenzo","family":"Oliva","sequence":"first","affiliation":[{"name":"Bipolar and Depressive Disorders Unit, Institute of Neurosciences, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, 170 Villarroel St., 12-0, 08036 Barcelona, Catalonia, Spain"},{"name":"Department of Biomedical and Neuromotor Sciences, University of Bologna, 40123 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2032-1181","authenticated-orcid":false,"given":"Michele","family":"De Prisco","sequence":"additional","affiliation":[{"name":"Bipolar and Depressive Disorders Unit, Institute of Neurosciences, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, 170 Villarroel St., 12-0, 08036 Barcelona, Catalonia, Spain"},{"name":"Section of Psychiatry, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University of Naples, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Teresa","family":"Pons-Cabrera","sequence":"additional","affiliation":[{"name":"Addictions Unit, Department of Psychiatry and Psychology, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, 170 Villarroel St., 12-0, 08036 Barcelona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Guzm\u00e1n","sequence":"additional","affiliation":[{"name":"Addictions Unit, Department of Psychiatry and Psychology, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, 170 Villarroel St., 12-0, 08036 Barcelona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6798-4054","authenticated-orcid":false,"given":"Gerard","family":"Anmella","sequence":"additional","affiliation":[{"name":"Bipolar and Depressive Disorders Unit, Institute of Neurosciences, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, 170 Villarroel St., 12-0, 08036 Barcelona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Hidalgo-Mazzei","sequence":"additional","affiliation":[{"name":"Bipolar and Depressive Disorders Unit, Institute of Neurosciences, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, 170 Villarroel St., 12-0, 08036 Barcelona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iria","family":"Grande","sequence":"additional","affiliation":[{"name":"Bipolar and Depressive Disorders Unit, Institute of Neurosciences, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, 170 Villarroel St., 12-0, 08036 Barcelona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7930-563X","authenticated-orcid":false,"given":"Giuseppe","family":"Fanelli","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, University of Bologna, 40123 Bologna, Italy"},{"name":"Department of Human Genetics, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, 6525 GD Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0276-7865","authenticated-orcid":false,"given":"Chiara","family":"Fabbri","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, University of Bologna, 40123 Bologna, Italy"},{"name":"Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King\u2019s College London, London SE5 9NU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4363-3759","authenticated-orcid":false,"given":"Alessandro","family":"Serretti","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, University of Bologna, 40123 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9647-0853","authenticated-orcid":false,"given":"Michele","family":"Fornaro","sequence":"additional","affiliation":[{"name":"Section of Psychiatry, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University of Naples, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felice","family":"Iasevoli","sequence":"additional","affiliation":[{"name":"Section of Psychiatry, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University of Naples, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"de Bartolomeis","sequence":"additional","affiliation":[{"name":"Section of Psychiatry, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University of Naples, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Murru","sequence":"additional","affiliation":[{"name":"Bipolar and Depressive Disorders Unit, Institute of Neurosciences, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, 170 Villarroel St., 12-0, 08036 Barcelona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0548-0053","authenticated-orcid":false,"given":"Eduard","family":"Vieta","sequence":"additional","affiliation":[{"name":"Bipolar and Depressive Disorders Unit, Institute of Neurosciences, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, 170 Villarroel St., 12-0, 08036 Barcelona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1785-7126","authenticated-orcid":false,"given":"Giovanna","family":"Fico","sequence":"additional","affiliation":[{"name":"Bipolar and Depressive Disorders Unit, Institute of Neurosciences, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, 170 Villarroel St., 12-0, 08036 Barcelona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1176\/appi.ajp.2009.09020299","article-title":"Impact of Substance Use Disorders on Recovery From Episodes of Depression in Bipolar Disorder Patients: Prospective Data From the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD)","volume":"167","author":"Ostacher","year":"2010","journal-title":"Am. J. Psychiatry"},{"key":"ref_2","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_3","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1177\/0004867415585855","article-title":"Prevalence and Impact of Comorbid Alcohol Use Disorder in Bipolar Disorder: A Prospective Follow-up Study","volume":"50","author":"Simhandl","year":"2016","journal-title":"Aust. N. Z. J. Psychiatry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.neubiorev.2019.04.004","article-title":"The Prevalence and Clinical Correlates of Cannabis Use and Cannabis Use Disorder among Patients with Bipolar Disorder: A Systematic Review with Meta-Analysis and Meta-Regression","volume":"101","author":"Pinto","year":"2019","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.neubiorev.2021.11.039","article-title":"The Prevalence, Odds, Predictors, and Management of Tobacco Use Disorder or Nicotine Dependence among People with Severe Mental Illness: Systematic Review and Meta-Analysis","volume":"132","author":"Fornaro","year":"2022","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_6","first-page":"1","article-title":"The Prevalence and Significance of Substance Use Disorders in Bipolar Type I and II Disorder","volume":"2","author":"Cerullo","year":"2007","journal-title":"Subst. Abus. Treat. Prev. Policy"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.4088\/JCP.v66n1001","article-title":"Prevalence, Correlates, and Comorbidity of Bipolar I Disorder and Axis I and II Disorders: Results from the National Epidemiologic Survery on Alcohol and Related Conditions","volume":"66","author":"Grant","year":"2005","journal-title":"J. Clin. Psychiatry"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.jad.2016.07.011","article-title":"Prevalence of Comorbid Bipolar and Substance Use Disorders in Clinical Settings, 1990\u20132015: Systematic Review and Meta-Analysis","volume":"206","author":"Hunt","year":"2016","journal-title":"J. Affect. Disord."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Lagerberg, T.V., Icick, R., Aminoff, S.R., Nerhus, M., Barrett, E.A., Bjella, T.D., Olsen, S.H., H\u00f8egh, M.C., and Melle, I. (2021). Substance Misuse Trajectories and Risk of Relapse in the Early Course of Bipolar Disorder. Front. Psychiatry, 12.","DOI":"10.3389\/fpsyt.2021.656912"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"203","DOI":"10.31887\/DCNS.2008.10.2\/rsmcintyre","article-title":"Medical and Substance-Related Comorbidity in Bipolar Disorder: Translational Research and Treatment Opportunities","volume":"10","author":"McIntyre","year":"2022","journal-title":"Dialog. Clin. Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s40263-019-00688-2","article-title":"Cognitive Impairment in Patients with Bipolar Disorder: Impact of Pharmacological Treatment","volume":"34","author":"Xu","year":"2020","journal-title":"CNS Drugs"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1034\/j.1399-5618.2003.00017.x","article-title":"Suicide Risk in Bipolar Patients: The Role of Co-Morbid Substance Use Disorders","volume":"5","author":"Dalton","year":"2003","journal-title":"Bipolar Disord."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1111\/j.1399-5618.2006.00349.x","article-title":"Aggression and Substance Abuse in Bipolar Disorder","volume":"8","author":"Grunebaum","year":"2006","journal-title":"Bipolar Disord."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/S2215-0366(15)00207-2","article-title":"Association between Alcohol and Substance Use Disorders and All-Cause and Cause-Specific Mortality in Schizophrenia, Bipolar Disorder, and Unipolar Depression: A Nationwide, Prospective, Register-Based Study","volume":"2","author":"Benros","year":"2015","journal-title":"Lancet Psychiatry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.jad.2008.08.019","article-title":"Clinical Features, Response to Treatment and Functional Outcome of Bipolar Disorder Patients with and without Co-Occurring Substance Use Disorder: 1-Year Follow-Up","volume":"115","author":"Mazza","year":"2009","journal-title":"J. Affect. Disord."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.schres.2007.11.034","article-title":"The Effectiveness of Antipsychotic Medications in Patients Who Use or Avoid Illicit Substances: Results from the CATIE Study","volume":"100","author":"Swartz","year":"2008","journal-title":"Schizophr. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1001\/jamapsychiatry.2015.0584","article-title":"Epidemiology of DSM-5 Alcohol Use Disorder: Results From the National Epidemiologic Survey on Alcohol and Related Conditions III","volume":"72","author":"Grant","year":"2015","journal-title":"JAMA Psychiatry"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1111\/ajad.12764","article-title":"Predictors of Initiation of Nicotine, Alcohol, Cannabis, and Cocaine Use: Results of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC)","volume":"27","author":"Blanco","year":"2018","journal-title":"Am. J. Addict."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.drugalcdep.2018.01.035","article-title":"Prevalence, Patterns, and Correlates of Multiple Substance Use Disorders among Adult Primary Care Patients","volume":"187","author":"John","year":"2018","journal-title":"Drug Alcohol Depend."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1034\/j.1399-5618.2001.30403.x","article-title":"Substance Abuse in Bipolar Disorder","volume":"3","author":"Cassidy","year":"2001","journal-title":"Bipolar Disord."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1001\/archpsyc.62.8.851","article-title":"Effects of Co-Occurring Alcohol Abuse on the Course of Bipolar Disorder Following a First Hospitalization for Mania","volume":"62","author":"Strakowski","year":"2005","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1001\/archpsyc.64.1.57","article-title":"Effects of Co-Occurring Cannabis Use Disorders on the Course of Bipolar Disorder after a First Hospitalization for Mania","volume":"64","author":"Strakowski","year":"2007","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_23","first-page":"223","article-title":"Machine Learning for Precision Psychiatry: Opportunities and Challenges","volume":"3","author":"Bzdok","year":"2018","journal-title":"Biol. Psychiatry Cogn. Neurosci. Neuroimag."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.euroneuro.2021.05.006","article-title":"Route Map for Machine Learning in Psychiatry: Absence of Bias, Reproducibility, and Utility","volume":"50","author":"Radua","year":"2021","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_25","first-page":"100144","article-title":"A Machine Learning Framework to Predict the Risk of Opioid Use Disorder","volume":"6","author":"Hasan","year":"2021","journal-title":"Mach. Learn. Appl."},{"key":"ref_26","first-page":"1","article-title":"Terciarismo En Psiquiatr\u00eda: El Programa de Trastornos Bipolares Del Cl\u00ednic de Barcelona","volume":"4","author":"Vieta","year":"2011","journal-title":"J. Psychiatry Ment. Health"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1177\/0269881116636545","article-title":"Evidence-Based Guidelines for Treating Bipolar Disorder: Revised Third Edition Recommendations from the British Association for Psychopharmacology","volume":"30","author":"Goodwin","year":"2016","journal-title":"J. Psychopharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1111\/bdi.13040","article-title":"Long-Term Treatment of Bipolar Disorder Type I: A Systematic and Critical Review of Clinical Guidelines with Derived Practice Algorithms","volume":"23","author":"Verdolini","year":"2020","journal-title":"Bipolar Disord."},{"key":"ref_29","unstructured":"APA (1994). Diagnostic and Statistical Manual of Mental Disorders, American Psychiatric Association. [4th ed.]."},{"key":"ref_30","unstructured":"APA (2000). Diagnostic and Statistical Manual of Mental Disorders, American Psychiatric Association. [4th ed.]. Text Rev."},{"key":"ref_31","unstructured":"APA (2013). Diagnostic and Statistical Manual of Mental Disorders: DSM-5, American Psychiatric Association (APA)."},{"key":"ref_32","unstructured":"First, M.B., Williams, J.B., Karg, R.S., and Spitzer, R.L. (2017). Structured Clinical Interview for DSM-5\u2014Research Version (SCID-5 for DSM-5, Research Version SCID-5-RV), American Psychiatric Association."},{"key":"ref_33","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_34","unstructured":"R Foundation for Statistical Computing, and R Core Team (2021). R: A Language and Environment for Statistical Computing, R Core Team."},{"key":"ref_35","unstructured":"Waring, E., Quinn, M., McNamara, A., de la Rubia, E.A., Zhu, H., Lowndes, J., Ellis, S., McLeod, H., Wickham, H., and M\u00fcller, K. (2022, June 08). Skimr: Compact and Flexible Summaries of Data, R Package, Version 1.0.7. Available online: https:\/\/CRAN.R-project.org\/package=skimr."},{"key":"ref_36","first-page":"1","article-title":"Ranger: A Fast Implementation of Random Forests for High Dimensional Data in C++ and R","volume":"77","year":"2017","journal-title":"J. Stat. Softw."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1023\/A:1010933404324","article-title":"Random Forests","volume":"45","author":"Breiman","year":"2001","journal-title":"Mach. Learn."},{"key":"ref_38","first-page":"18","article-title":"Classification and Regression by RandomForest","volume":"2","author":"Liaw","year":"2002","journal-title":"R News"},{"key":"ref_39","unstructured":"Kuhn, M. (2022, June 08). Caret: Classification and Regression Training, R Package Version 6.0-71. Available online: https:\/\/CRAN.R-project.org\/package=caret."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"82","DOI":"10.32614\/RJ-2014-008","article-title":"ROSE: A Package for Binary Imbalanced Learning","volume":"6","author":"Lunardon","year":"2014","journal-title":"R J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1176\/appi.ajp.162.5.1008","article-title":"Substance Abuse in First-Episode Bipolar I Disorder: Indications for Early Intervention","volume":"162","author":"Baethge","year":"2005","journal-title":"Am. J. Psychiatry"},{"key":"ref_42","unstructured":"Minato Nakazawa, M. (2022, June 08). Package \u201cfmsb\u201d Title Functions for Medical Statistics Book with Some Demographic Data Depends R (>= 2.2.0). Available online: https:\/\/cran.r-project.org\/web\/packages\/fmsb\/fmsb.pdf."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.jad.2022.02.042","article-title":"Undetermined Predominant Polarity in a Cohort of Bipolar Disorder Patients: Prevalent, Severe, and Overlooked","volume":"303","author":"Fico","year":"2022","journal-title":"J. Affect. Disord."},{"key":"ref_44","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_45","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1590\/1516-4446-2014-1459","article-title":"Personality Disorders in Euthymic Bipolar Patients: A Systematic Review","volume":"37","author":"Studart","year":"2015","journal-title":"Rev. Bras. Psiquiatr."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1111\/acps.12777","article-title":"Aggressiveness in Depression: A Neglected Symptom Possibly Associated with Bipolarity and Mixed Features","volume":"136","author":"Verdolini","year":"2017","journal-title":"Acta Psychiatr. Scand."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.jad.2015.04.024","article-title":"Misdiagnosis, Duration of Untreated Illness (DUI) and Outcome in Bipolar Patients with Psychotic Symptoms: A Naturalistic Study","volume":"182","author":"Altamura","year":"2015","journal-title":"J. Affect. Disord."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1111\/acps.12170","article-title":"Antecedents of Manic versus Other First-Psychotic Episodes in 263 Bipolar-I Disorder Patients","volume":"129","author":"Salvatore","year":"2014","journal-title":"Acta. Psychiatr. Scand."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1017\/S0033291718001678","article-title":"Clinical Course Predicts Long-Term Outcomes in Bipolar Disorder","volume":"49","author":"Uher","year":"2019","journal-title":"Psychol. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.euroneuro.2006.10.002","article-title":"Impulsivity and Bipolar Disorder","volume":"17","author":"Najt","year":"2007","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.eurpsy.2014.06.005","article-title":"Bipolar I and II versus Unipolar Depression: Clinical Differences and Impulsivity\/Aggression Traits","volume":"30","author":"Dervic","year":"2015","journal-title":"Eur. Psychiatry"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1111\/j.1399-5618.2004.00110.x","article-title":"Impulsivity: A Link between Bipolar Disorder and Substance Abuse","volume":"6","author":"Swann","year":"2004","journal-title":"Bipolar Disord."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"155","DOI":"10.31887\/DCNS.2013.15.2\/mzimmerman","article-title":"The Relationship between Borderline Personality Disorder and Bipolar Disorder","volume":"15","author":"Zimmerman","year":"2013","journal-title":"Dialogues Clin. Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e1155","DOI":"10.1038\/tp.2017.115","article-title":"Genome-Wide Association Study of Borderline Personality Disorder Reveals Genetic Overlap with Bipolar Disorder, Major Depression and Schizophrenia","volume":"7","author":"Witt","year":"2017","journal-title":"Transl. Psychiatry"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.jpsychires.2009.09.011","article-title":"Borderline Personality Disorder and the Misdiagnosis of Bipolar Disorder","volume":"44","author":"Ruggero","year":"2010","journal-title":"J. Psychiatr. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.euroneuro.2022.02.007","article-title":"Are Personality Disorders in Bipolar Patients More Frequent in the US than Europe?","volume":"58","author":"Post","year":"2022","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1097\/NMD.0000000000000235","article-title":"Comorbid Bipolar Disorder and Borderline Personality Disorder and Substance Use Disorder","volume":"203","author":"Walsh","year":"2015","journal-title":"J. Nerv. Ment. Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijpsycho.2019.08.003","article-title":"Neural Mechanisms of Affective Instability and Cognitive Control in Substance Use","volume":"146","author":"Bodkyn","year":"2019","journal-title":"Int. J. Psychophysiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.addbeh.2008.10.020","article-title":"Marriage and Relationship Closeness as Predictors of Cocaine and Heroin Use","volume":"34","author":"Heinz","year":"2009","journal-title":"Addict. Behav."},{"key":"ref_60","first-page":"1","article-title":"Socio-Economic Functioning in Patients with Bipolar Disorder and Their Unaffected Siblings\u2014Results from a Nation-Wide Population-Based Longitudinal Study","volume":"2021","author":"Sletved","year":"2021","journal-title":"Psychol. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.euroneuro.2021.03.015","article-title":"The Effect of Family Environment and Psychiatric Family History on Psychosocial Functioning in First-Episode Psychosis at Baseline and after 2 Years","volume":"49","author":"Verdolini","year":"2021","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1111\/add.15680","article-title":"Genome-Wide Analysis Reveals Genetic Overlap between Alcohol Use Behaviours, Schizophrenia and Bipolar Disorder and Identifies Novel Shared Risk Loci","volume":"117","author":"Karadag","year":"2022","journal-title":"Addiction"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"409","DOI":"10.2174\/1570159X14666160607101400","article-title":"Who\u2019s the Leader, Mania or Depression? Predominant Polarity and Alcohol\/Polysubstance Use in Bipolar Disorders","volume":"15","author":"Janiri","year":"2017","journal-title":"Curr. Neuropharmacol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.jad.2016.09.062","article-title":"Alcohol Use Disorders Are Associated with Increased Affective Lability in Bipolar Disorder","volume":"208","author":"Lagerberg","year":"2017","journal-title":"J. Affect. Disord."},{"key":"ref_65","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_66","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1111\/acps.12204","article-title":"First-Episode Types in Bipolar Disorder: Predictive Associations with Later Illness","volume":"129","author":"Baldessarini","year":"2014","journal-title":"Acta Psychiatr. Scand."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1016\/j.jad.2018.12.093","article-title":"Predominant Polarity in Bipolar I and II Disorders: A Five-Year Follow-up Study","volume":"246","author":"Pallaskorpi","year":"2019","journal-title":"J. Affect. Disord."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/j.psychres.2018.10.073","article-title":"Factors Predicting Re-Hospitalization for Inpatients with Bipolar Mania\u2014A Naturalistic Cohort","volume":"270","author":"Li","year":"2018","journal-title":"Psychiatry Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.neubiorev.2020.09.015","article-title":"The Biology of Aggressive Behavior in Bipolar Disorder: A Systematic Review","volume":"119","author":"Fico","year":"2020","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1080\/15622970701558488","article-title":"Bipolar Disorder Preceded by Substance Abuse: A Different Phenotype with Not so Poor Outcome?","volume":"10","author":"Pacchiarotti","year":"2009","journal-title":"World J. Biol. Psychiatry"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1111\/j.1399-5618.2007.00465.x","article-title":"Is Bipolar Disorder Overdiagnosed among Patients with Substance Abuse?","volume":"9","author":"Stewart","year":"2007","journal-title":"Bipolar Disord."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.euroneuro.2021.03.008","article-title":"Bipolar Disorder Cohort Studies: Crucial, but Underfunded","volume":"47","author":"Vieta","year":"2021","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"142","DOI":"10.20882\/adicciones.1559","article-title":"Gu\u00eda de Pr\u00e1ctica Cl\u00ednica Para El Tratamiento Farmacol\u00f3gico y Psicol\u00f3gico de Los Pacientes Adultos Con Trastorno Bipolar y Un Diagn\u00f3stico Com\u00f3rbido de Trastorno Por Uso de Sustancias","volume":"34","author":"Goikolea","year":"2021","journal-title":"Adicciones"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"660432","DOI":"10.3389\/fpsyt.2021.660432","article-title":"Comorbid Bipolar and Alcohol Use Disorder\u2014A Therapeutic Challenge","volume":"12","author":"Grunze","year":"2021","journal-title":"Front. Psychiatry"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1034\/j.1600-0447.2000.102006432.x","article-title":"Psychoactive Substance Use Diagnoses among Psychiatric In-Patients","volume":"102","author":"Hansen","year":"2000","journal-title":"Acta Psychiatr. Scand."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/14\/3935\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:43:28Z","timestamp":1760139808000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/14\/3935"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,6]]},"references-count":75,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["jcm11143935"],"URL":"https:\/\/doi.org\/10.3390\/jcm11143935","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,6]]}}}