title: Precursors of bipolar disorders: a systematic literature review of prospective studies.
abstract: OBJECTIVE
  To evaluate the presence of affective signs and symptoms as precursors of bipolar disorder in prospective studies, including assessment of their prevalence, duration, and predictive value.
  
  
  METHODS
  We followed PRISMA guidelines to search PubMed, CINAHL, PsycINFO, EMBASE, SCOPUS, and ISI Web of Science databases to May 31, 2013, using the terms bipolar disorder AND (antecedent* OR predict* OR prodrom* OR prospect*) AND (diagnosis OR development). Hand searching of identified reports led to additional relevant references.
  
  
  METHODS
  We included only English-language articles containing (1) prospective, longitudinal studies with at least 2 structured clinical assessments (intake and follow-up); (2) no previous DSM-III or DSM-IV diagnoses of bipolar I or bipolar II; and (3) diagnostic outcome of bipolar I or bipolar II. Studies of subjects at familial risk of bipolar disorder were excluded, as these have been reviewed elsewhere.
  
  
  METHODS
  We tabulated details of study design, outcomes, precursors, and predictive value. Only studies reporting a positive predictive association were included.
  
  
  RESULTS
  In 26 published reports meeting selection criteria, methods varied widely in terms of design, duration of follow-up, ages, and populations investigated. Despite such heterogeneity in methods, findings were notably consistent. Precursors of bipolar disorder include mood lability, subsyndromal and major depression, subsyndromal hypomanic symptoms with or without major depression, cyclothymia and bipolar not otherwise specified, major depression with psychotic features, and other psychotic disorders. Bipolar disorder was also predicted by juvenile onset of major depression as well as frequency and loading of hypomanic or depressive symptoms.
  
  
  CONCLUSIONS
  Despite the limitations of published reports, prospectively identified precursors of bipolar disorder typically arose years prior to syndromal onset, often with significant early morbidity and disability. Prospectively identified precursors of bipolar disorder are generally consistent with findings in retrospective and family-risk studies. Combining precursors and other risk factors may increase predictive value, support earlier diagnosis, improve treatment, and limit disability in bipolar disorder.
authors.affiliation: 245 East 50th St, Ste 2A, New York, NY 10022 moodcenter@gmail.com.
authors.forename: Gianni L
authors.initials: GL
authors.lastname: Faedda
authors.forename: Ciro
authors.initials: C
authors.lastname: Marangoni
authors.forename: Giulia
authors.initials: G
authors.lastname: Serra
authors.forename: Paola
authors.initials: P
authors.lastname: Salvatore
authors.forename: Gabriele
authors.initials: G
authors.lastname: Sani
authors.forename: Gustavo H
authors.initials: GH
authors.lastname: Vázquez
authors.forename: Leonardo
authors.initials: L
authors.lastname: Tondo
authors.forename: Paolo
authors.initials: P
authors.lastname: Girardi
authors.forename: Ross J
authors.initials: RJ
authors.lastname: Baldessarini
authors.forename: Athanasios
authors.initials: A
authors.lastname: Koukopoulos
mesh_terms: D001714:Bipolar Disorder / Q000175:diagnosis / Q000453:epidemiology*; D006801:Humans; D062706:Prodromal Symptoms