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Dean F. MacKinnon, MD; Peter P. Zandi, PhD; Elliot Gershon, MD; John I. Nurnberger, Jr, MD, PhD; Theodore Reich, MD; J. Raymond DePaulo, MD

Arch Gen Psychiatry. 2003;60:921-928.

Background  Heterogeneity within the diagnostic construct of bipolar disorder is most likely an obstacle to discovering its causes. Phenomena in the bipolar spectrum, including rapid cycling, cyclothymia, and affective instability of borderline personality, may be important markers of etiologic heterogeneity. Rapid switching of mood may be central to these phenomena.

Methods  We performed a case-control study, using diagnostic data from a multisite bipolar disorder linkage study, to explore clinical and demographic factors potentially related to rapid switching in bipolar disorder. Participants were 18 years or older and members of a family in which 2 or more first-degree relatives had bipolar disorder. Of 718 individuals interviewed and diagnosed as having bipolar disorder, 603 gave sufficient information about rapid switching and thus constituted the study group (60% female; mean age, 41 years; and mean education level, 13.8 years).

Results  Rapid switching of mood was reported by 44% of interviewees and was associated with early age at onset of bipolar disorder, higher risk of anxiety and substance abuse or dependence comorbidity, suicide attempts, antidepressant drug use, and having a relative with rapid switching.

Conclusions  Rapid switching is associated with a complex clinical course of bipolar disorder. These results extend previous associations among rapid switching, anxiety, substance abuse, and early onset of bipolar disorder to a family study population. Rapid switching of mood seems to be the core phenomenon behind several variants of non–DSM-IV rapid cycling, DSM-III-R mixed states, and borderline personality disorder and the link connecting comorbidity, suicide, and early onset of bipolar disorder. Further biological investigation of the rapid-switching phenomenon is justified on epidemiologic grounds.

From the Department of Psychiatry and Behavioral Sciences (Drs MacKinnon and DePaulo) and the Bloomberg School of Public Health (Dr Zandi), The Johns Hopkins University School of Medicine, Baltimore, Md; the Department of Psychiatry, University of Chicago, Chicago, Ill (Dr Gershon); the Institute of Psychiatric Research, Department of Psychiatry, Indiana University School of Medicine, Indianapolis (Dr Nurnberger); and the Department of Psychiatry, Washington University, St Louis, Mo (Dr Reich).

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