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Clinical and Environmental Risk Factors for Bipolar Disorder

Review of Prospective Studies

Marangoni, Ciro MD; Faedda, Gianni L. MD; Baldessarini, Ross J. MD

doi: 10.1097/HRP.0000000000000161

Learning objectives After participating in this activity, learners should be better able to:

• Evaluate factors that have been identified in prospective studies as predicting the onset of bipolar disorder

The prodromal phase of bipolar disorder (BD) remains incompletely characterized, limiting early detection of BD and delaying interventions that might limit future morbidity and disability. Retrospective and family-risk studies have consistently found evidence of prodromal psychopathology in subjects later diagnosed with BD. Here, we review prospective studies of clinical risk factors and exposures identified before diagnosis of BD: our findings are consistent with those from retrospective and family-risk studies. Affective psychopathology often precedes diagnosis to suggest a homotypic trajectory in developing BD. Early non-affective (heterotypic) psychopathological disturbances, including anxiety and disruptive behavior disorders, as well as environmental factors and exposures, have been found in prospective studies to increase the risk of BD, but tend to lack specificity in predicting BD. Findings from prospective studies are encouragingly similar to those of retrospective and family-risk studies.

From the International Consortium for Bipolar and Psychotic Disorders Research, Mailman Research Center, McLean Hospital, Belmont, MA; Lucio Bini Mood Disorders Center, New York, NY (Dr. Faedda); New York University Child Study Center, Department of Child and Adolescent Psychiatry (Dr. Faedda); Harvard Medical School (Dr. Baldessarini).

Original manuscript received 2 November 2016, accepted for publication subject to revision 13 January 2017; revised manuscript received 11 February 2017.

Correspondence: Ciro Marangoni, MD, International Consortium for Bipolar and Psychotic Disorders Research, Mailman Research Center, McLean Hospital, 115 Mill St., Belmont, MA 02478. Email:

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