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A high proportion of people with major depression may actually have a "hidden" form of bipolar disorder, according to a population-based study.

Interviews with a nationally-representative sample of more than 9,000 people suggest that nearly 40% of people with a history of major depressive disorder report periods of hypomania that just miss the threshold for a bipolar diagnosis, reported Kathleen R. Merikangas, PhD, of the National Institute of Mental Health in Bethesda, Md., and colleagues.

The group with subthreshold hypomania appeared to fall between pure depression and bipolar disorder for clinical severity, the researchers reported online in the American Journal of Psychiatry.

Since such patients might benefit from the addition of a mood stabilizer after response to antidepressants, the researchers supported a proposed broadening of the criteria for bipolar disorder.

Subthreshold mania hasn't made it into the current edition of the Diagnostic and Statistical Manual of Mental Diseases (DSM-IV), but changes are being debated as the psychiatric "bible" undergoes revision for its fifth edition, expected in 2013.

A diagnostic specifier for subthreshold bipolarity might fit well in the diagnostic category of major depression, Merikangas' group suggested.

"Such an expansion of the bipolar concept would likely lead to important changes in the treatment of patients who are undiagnosed or misdiagnosed despite elevated morbidity and mortality rates," they wrote in the paper.

Regardless, if there is such a substantial group of patients with hidden bipolarity, careful evaluation of a history of hypomanic symptoms and a family history of mania would be critical, Merikangas and colleagues noted.

The group analyzed results from the nationally-representative National Comorbidity Survey Replication (NCS-R) -- a nationally representative face-to-face household survey of the prevalence and correlates of a wide range of DSM-IV mental disorders, according to background supplied by the authors.

For the current study, responses were analyzed from 9,282 people surveyed between February 2001 and April 2003.

Overall, 5.4% of the NCS-R respondents met criteria for major depressive disorder alone over the prior 12 months, jumping to 10.2% for lifetime prevalence.

Together, the bipolar spectrum conditions were nearly as common as major depression alone.

The lifetime prevalence of major depression with subthreshold hypomania in the NCS-R respondents was 6.7% and 2.2% over the prior 12 months.

Bipolar I disorder -- major depressive disorder with mania -- affected 0.3% of the respondents over the prior 12 months and 0.7% over their lifetime.

Bipolar II disorder -- major depressive disorder with hypomania -- affected 0.8% of the respondents over the prior 12 months, with a 1.6% lifetime prevalence.

Treatment for mood disorders was no more likely for those with subthreshold hypomania than for those with depression alone.

However, the subthreshold hypomania group showed greater rates of comorbidity than the depression alone group for the following (P<0.05 for all):

• Anxiety (72.2% versus 52.6%)
• Substance use disorders (35.3% versus 18.0%)
• Behavioral problems (41.1% versus 19.2%)

Suicide attempts were reported by 41% of those with major depression and subthreshold hypomania, which fell between the 50% of those with bipolar II and the 31% of those with major depression alone.

Age at first onset showed the same pattern as did number of episodes of depression.

These differences in clinical characteristics "underscore the heterogeneity of major depression and support the notion that a critical reappraisal of diagnostic criteria for mood disorders is warranted," the researchers wrote in the paper.

Even more convincing, they suggested, was that family history of mania was as common for those with subthreshold hypomania as for those with mania or hypomania (76.0% versus 70.4% and 67.8%, respectively).

The findings provide the first comparisons of the prevalence and clinical correlates of bipolar II disorder, major depression with subthreshold hypomania, and major depression alone in a nationally representative U.S. sample, according to Merikangas and colleagues.

However, the researchers noted that the data were based on self-report in the lay-administered NCS-R survey, and precluded collection of information on the full spectrum of expression of bipolar disorder proposed in recent studies.

The authors also cautioned that their definition of subthreshold bipolar disorder -- which required a major depressive episode diagnosis and a "yes" answer to either of the mania screening questions that encompassed a discrete period of increased energy, activity, and euphoria or irritability not related to impairment in daily activities -- was more restrictive than the definitions proposed by clinical researchers.

Thus, they concluded, the study may have underestimated the prevalence of bipolar spectrum disorder in the population.

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