Background: Mixed depression (MxD), i.e. depression plus cooccurring noneuphoric manic/hypomanic symptoms, questions the current categorical dividing of mood disorders into bipolar disorders and depressive disorders, and supports a dimensional approach. The study aim was to test a dimensional approach to mood disorders by looking for a progressive grading of age at onset and bipolar family history loading between bipolar II disorder (BP-II) and major depressive disorder (MDD). Methods: Consecutive 389 BP-II and 261 MDD major depressive episode outpatients were interviewed (off psychoactive drugs) with the Structured Clinical Interview for DSM-IV, the Hypomania Interview Guide (to assess intradepressive noneuphoric hypomanic symptoms), and the Family History Screen, by a mood disorder specialist psychiatrist in a private practice. BP-II and MDD MxD and non-MxD were compared on age at onset and bipolar family history loading (the diagnostic validators). A dose-response was tested between the number of intradepressive hypomanic symptoms and bipolar family history loading, and a correlation was tested between the number of intradepressive hypomanic symptoms and age at onset. Results: MxD was present in 64.5% of BP-II and in 32.1% of MDD. There were significant differences in classic diagnostic validators (onset age, bipolar family history). The comparisons between BP-II and MDD MxD and non-MxD on age at onset and bipolar family history found a clear and significant grading in age at onset from BP-II MxD to MDD non-MxD (a progressive increase), and a clear and significant grading in bipolar family history loading from BP-II MxD to MDD non-MxD (a progressive decrease). A dose-response relationship was found between the number of intradepressive hypomanic symptoms and bipolar family history loading. The area under the ROC curve was small. A significant correlation was found between the number of intradepressive hypomanic symptoms and age at onset. Conclusions: The presence of MxD in a significant proportion of MDD, the progressive grading of age at onset and bipolar family history from BP-II MxD to MDD non-MxD, the dose-response relationship between intradepressive hypomanic symptoms and bipolar family history loading, and the correlation between intradepressive hypomanic symptoms and age at onset could support a dimensional approach to mood disorders (BP-II and MDD). On the other hand, the significant differences on classic diagnostic validators could support a categorical distinction. A mixed approach (dimensional and categorical) to mood disorders could be supported.

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