Our knowledge of the comorbidity of mood disorders depends heavily on their diagnostic classification, which is currently in a state of flux.

A diagnostic specifier for bipolarity was developed and applied to data collected on major depression in several studies: Zurich Study, EDSP Study Munich, NCS-R Study USA, and Bridge Study (Vieta et al. 2010).

In all four studies, about 40% of DSM-IV major depressive disorder diagnoses were re-classified as sub-threshold bipolar II disorders, resulting in a major change in comorbidity. The comorbidity of major depression with substance use disorder (SUD) (especially alcohol use) and panic disorder shifted substantially towards an association with hidden bipolar depression. The highest comorbidity was found in bipolar-I disorders. Pure and preponderantly manic or hypomanic subjects seem to be protected against comorbidity with anxiety disorders but are at risk for SUD.

The current classification of mood disorders over-estimates a diagnosis of pure depression. New data suggest that 40% to 50% of all subjects with mood disorders are bipolars. This has a considerable impact on comorbidity, treatment and future research. Self-assessment instruments for the detection of hypomania are recommendable.