Gianni L Faedda1, Giulia Serra2, Ciro Marangoni3, Paola Salvatore4, Gabriele Sani5, Gustavo H Vázquez6, Leonardo Tondo7, Paolo Girardi8, Ross J Baldessarini9, Athanasios Koukopoulos10. 1. 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. 2. 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. 3. Section of Neurological, Psychiatric and Psychological Sciences, Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Italy. 4. 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. 5. 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. 6. International Consortium for Bipolar Disorder Research, McLean Hospital, Belmont, MA, United States; Department of Neuroscience, University of Palermo, Buenos Aires, Argentina. 7. 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. 8. 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. 9. International Consortium for Bipolar Disorder Research, McLean Hospital, Belmont, MA, United States; Department of Psychiatry, Harvard Medical School, Boston, MA, United States. 10. Centro Lucio Bini, Rome, Italy.
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. LIMITATIONS: 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.
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. LIMITATIONS: 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.
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