Converging evidence from clinical and epidemiologic studies suggests that the current diagnostic criteria for bipolar II disorder fail to include milder but clinically significant bipolar syndromes, and that a significant percentage of these conditions are diagnosed by default as unipolar major depression (6
). Using data from a nationally-representative sample, the present investigation examined the validity of characterizing sub-threshold bipolarity as a source of heterogeneity in major depressive disorder (6
). Its principal aims were to estimate the prevalence of these categories of the bipolar spectrum and to compare the clinical characteristics of major depression with Sub-threshold Hypomania to other bipolar disorders as well as to MDD alone.
Application of the present categories revealed considerable diversity in the clinical manifestations of mood disorders and indicate that bipolar spectrum disorders are almost as frequent as ‘pure’ unipolar depression. However, the question of perhaps greatest importance to mood disorder research and clinical practice concerns the appropriateness of diagnosing major depression in individuals who also have Sub-threshold Hypomania. This subtype of mood disorder corresponds to 39% of all cases of unipolar major depression in the general population, and it was not found to differ from depression alone in terms of lifetime or 12-month treatment for mood disorders. While these findings are consistent with past research demonstrating that Sub-threshold Hypomania is often subsumed under the category of unipolar depression (8
), important differences were nonetheless observed in the clinical characteristics of these categories. Individuals with MDD and Sub-threshold Hypomania had a younger age of disorder onset, greater rates of comorbidity, more episodes of depression and a trend towards more suicide attempts compared to individuals with MDD alone. Considered jointly with reported differences in response to pharmacotherapy between these forms of mood disorder (15
), the present findings underscore the heterogeneity of major depression and support the notion that a critical reappraisal of diagnostic criteria for mood disorders is warranted.
Differences were also observed for markers of clinical severity or history when comparing individuals with MDD and Sub-threshold Hypomania to those meeting criteria for bipolar II disorder. However, these findings reflect the greater general severity in bipolar II disorder rather than differences in the basic expression of depressive or hypomanic syndromes. Perhaps the most convincing evidence for inclusion of the concept of sub-threshold hypomania is the finding that a family history of mania is equally common among those with sub-threshold hypomania as with threshold mania. Although the family history was based on report by the respondents, it is unlikely that there would be differential bias by the various mania/hypomania subgroups. As these differences are quantitative in nature, they are consistent with conceptualization of depression with sub-threshold hypomania as a milder manifestation of bipolar disorder as described nearly a century ago (34
) and whose pertinence has been reemphasized since the introduction of modern diagnostic systems (8
). The inclusion of Sub-threshold Hypomania among those with MDD in the diagnosis of bipolar disorders would have a far reaching impact on a number of scientific disciplines, ranging from descriptive and analytic epidemiology to genetic research, whose progress depends on validity of mood disorder phenotypes. Most importantly, 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 (36
The present findings also have important clinical implications for the evaluation of mood disorders. If there is a substantial group of major depressives who manifest hidden bipolarity, it would be critical to include careful evaluation of a history of hypomania symptoms and family history of mania. In fact, based on the convergence of findings across international samples as well as emerging evidence from clinical studies, a diagnostic specifier for sub-threshold bipolarity in the diagnostic category of major depression has been proposed (6
). Despite the widespread clinical belief that antidepressants may trigger bipolar symptoms in susceptible individuals, empirical evidence for this is lacking (19
). However, addition of a mood stabilizer after response to antidepressant treatment may be beneficial in those who manifest sub-threshold bipolarity (38
The present results provide the first comparisons of the prevalence and clinical correlates of BP- II disorder, MDD with Sub-threshold Hypomania, and MDD alone in a nationally-representative U.S. sample. These findings confirm those of a population-based study of young adults which also revealed that nearly 40% of those with major depression may manifest bipolar disorder. Concerning limitations of this study that should be considered in interpreting the findings, the use of the fully structured, lay-administered CIDI precluded the collection of information on the full spectrum of expression of bipolar disorder proposed in recent studies (7
). Although we could not modify the thresholds for some of the diagnostic criteria for mania and depression, our definition of sub-threshold bipolar disorder is still more restrictive than the definitions proposed by clinical researchers. Therefore, our prevalence estimate of sub-threshold bipolar disorder is likely to underestimate bipolar spectrum disorder in the population. Although the clinical reappraisal study found good concordance of CIDI diagnoses with blinded clinical diagnoses based on the SCID, concordance was lower for Bipolar-II and sub-threshold bipolar disorder than for Bipolar Disorder-I (25
). The less flexible nature of the CIDI in comparison to clinical interviews could have also led to overestimation of comorbidity and potentially influence clinical severity markers. Differences between the 1-year recall period of the symptom scales used in the present study and those for which the scales were standardized diminish the comparability of the present findings with those of previous clinical samples. In addition, the prevalence of mania in family members was not assessed in all groups. Finally, although the prevalence of bipolar disorder would be expected to increase if diagnostic criteria were expanded to include MDD with Sub-threshold Mania, there would not be an increase in the overall prevalence of mood disorders because there would be a concomitant decrease in the rates of major depression. This risk should be examined critically but weighed against prospective evidence that youth with Major Depressive episodes plus Sub-threshold Mania have a high probability of conversion to bipolar-I disorder (6
) and that milder manifestations of the bipolar spectrum can be distinguished from major depression in severity, course, and comorbidity.