title: Clinical risk factors for bipolar disorders: a systematic review of prospective studies.
abstract: BACKGROUND
  Early phases and suspected precursor states of bipolar disorder are not well characterized. We evaluate the prevalence, duration, clinical features and predictive value of non-affective psychopathology as clinical risk factors for bipolar disorder in prospective studies.
  
  
  METHODS
  We screened PubMed, CINAHL, PsycINFO, Embase, SCOPUS, and ISI-Web of Science databases from inception up to January 31, 2014, following PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and searched: bipolar disorder AND [antecedent⁎ OR predict⁎ OR prodrom⁎ OR prospect⁎ OR risk⁎] AND [diagnosis OR development]. We included only English language reports on prospective, longitudinal studies with two structured clinical assessments (intake and follow-up); no DSM intake diagnosis of bipolar-I or -II; diagnostic outcome was bipolar-I or -II. Details of study design, risk factors, and predictive value were tabulated.
  
  
  RESULTS
  We found 16 published reports meeting selection criteria, with varying study design. Despite heterogeneity in methods, findings across studies were consistent. Clinical risk factors of bipolar disorder were early-onset panic attacks and disorder, separation anxiety and generalized anxiety disorders, conduct symptoms and disorder, ADHD, impulsivity and criminal behavior.
  
  
  CONCLUSIONS
  Since risk factors identified in some prospective studies are predictive of other conditions besides bipolar disorder, these preliminary findings require replication, and their sensitivity, specificity and predictive value need to be assessed.
  
  
  CONCLUSIONS
  Clinical risk factors for bipolar disorder typically arise years prior to syndromal onset, include anxiety and behavioral disorders with unclear sensitivity and specificity. Prospectively identified clinical risk factors for bipolar disorder are consistent with retrospective and family-risk studies. Combining clinical risk factors with precursors and family-risk may improve early identification and timely and appropriate treatment of bipolar disorder.
authors.affiliation: Lucio Bini Mood Disorders Center, New York, NY, United States; New York University Medical Center & Child Study Center, New York, NY, United States; International Consortium for Bipolar Disorder Research, McLean Hospital, Belmont, MA, United States. Electronic address: moodcenter@gmail.com.
authors.forename: Gianni L
authors.initials: GL
authors.lastname: Faedda
authors.affiliation: Centro Lucio Bini, Rome, Italy; NESMOS Department (Neuroscience, Mental Health and Sensory Organs), "La Sapienza" University School of Medicine and Psychology, and Lithium Clinic, Sant'Andrea Hospital, Rome, Italy; Department of Psychiatry, Harvard Medical School, Boston, MA, United States.
authors.forename: Giulia
authors.initials: G
authors.lastname: Serra
authors.affiliation: Section of Neurological, Psychiatric and Psychological Sciences, Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Italy.
authors.forename: Ciro
authors.initials: C
authors.lastname: Marangoni
authors.affiliation: International Consortium for Bipolar Disorder Research, McLean Hospital, Belmont, MA, United States; Department of Psychiatry, Harvard Medical School, Boston, MA, United States; Section of Psychiatry, Department of Neuroscience, University of Parma, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Salvatore
authors.affiliation: Centro Lucio Bini, Rome, Italy; NESMOS Department (Neuroscience, Mental Health and Sensory Organs), "La Sapienza" University School of Medicine and Psychology, and Lithium Clinic, Sant'Andrea Hospital, Rome, Italy; IRCCS Santa Lucia Foundation, Department of Clinical and Behavioral Neurology, Neuropsychiatry Laboratory, "La Sapienza" University School of Medicine, Rome, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Sani
authors.affiliation: International Consortium for Bipolar Disorder Research, McLean Hospital, Belmont, MA, United States; Department of Neuroscience, University of Palermo, Buenos Aires, Argentina.
authors.forename: Gustavo H
authors.initials: GH
authors.lastname: Vázquez
authors.affiliation: International Consortium for Bipolar Disorder Research, McLean Hospital, Belmont, MA, United States; Centro Lucio Bini, Rome, Italy; Department of Psychiatry, Harvard Medical School, Boston, MA, United States; Centro Lucio Bini, Cagliari, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Tondo
authors.affiliation: Centro Lucio Bini, Rome, Italy; NESMOS Department (Neuroscience, Mental Health and Sensory Organs), "La Sapienza" University School of Medicine and Psychology, and Lithium Clinic, Sant'Andrea Hospital, Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Girardi
authors.affiliation: International Consortium for Bipolar Disorder Research, McLean Hospital, Belmont, MA, United States; Department of Psychiatry, Harvard Medical School, Boston, MA, United States.
authors.forename: Ross J
authors.initials: RJ
authors.lastname: Baldessarini
authors.affiliation: Centro Lucio Bini, Rome, Italy.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Koukopoulos
mesh_terms: D001008:Anxiety Disorders / Q000453:epidemiology; D001289:Attention Deficit Disorder with Hyperactivity / Q000453:epidemiology; D001714:Bipolar Disorder / Q000175:diagnosis* / Q000453:epidemiology*; D015897:Comorbidity; D003415:Crime / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D007175:Impulsive Behavior; D016584:Panic Disorder / Q000453:epidemiology; D015995:Prevalence; D011446:Prospective Studies; D012189:Retrospective Studies; D012307:Risk Factors
keywords: Adolescent; Bipolar disorder; Child; Depression; Prodrome; Risk factor