Bipolar Disorders: Mixed States, Rapid-Cycling, and Atypical Forms

125 Recurrent brief depressionWe found a transition from RBD to MDD in 14% of cases and the reversetransition in 25% of cases (Angst, 1990). These findings have been recentlysupported by another epidemiological study in adolescents and young adults(Pezawas et al., 2003). RBD is therefore best considered as one of many coursepatterns of the natural history of depression. Moreover, it is clearly not the case thatpatients suffering from recurrent major depression experience only major episodes.It is well established that half of such patients manifest multiple brief episodes ofdepression and in addition depressive symptoms under the threshold of RBD orminor depression, including symptom-free intervals in between. This has recentlyalso been reported by Judd et al.(1998) on the basis of a prospective long-term studyof depression and bipolar disorders (Judd et al., 2002, 2003). We would like to seeRBD established as a firm subgroup of the dimension of depression, ranging fromsymptoms to severe episodes. This seems to be the most plausible concept.A further-reaching interpretation would be that RBD is the manifest clinicalexpression of a persisting instability of mood regulation, which may also beexpressed as a lowered threshold for exhibiting mood symptoms on stressful lifeevents. RBD patients might be more prone to exhibit depressive symptoms in thepresence of stressful environmental factors. This hypothesis is supported by theEarly Developmental Stages of Psychopathology study (Pezawas et al., 2003),which found a strong relationship between posttraumatic stress disorder andRBD. The irregular pattern of occurrences of depressive symptoms which arelinked to stressful events also supports this hypothesis (Pezawas et al., 2002a).This interpretation would be compatible with the idea of a premorbid personalityor chronic low-threshold mood disorder, which is characterized by RBD andfrequent ups and downs. The latter has been shown to be a risk and/or vulnerabilityfactor for mood disorders (especially for BP-II). These frequent ups and downs as apersonality feature seem to be independent of the positive family history for BP anddepression (Angst et al., 2003b). This etiological model postulates two independenttypes of risk factors: (1) family occurrence of mood disorders; and (2) unstablemood regulation. We could speculate that suicidal behavior and such mood labilityshare the same underlying biological factor. Mood stabilizers may influence thebiological mood lability. This hypothesis is supported by a single case analysis(Pazzaglia et al., 1993) and a case report (Corominas et al., 1998).Treatment of RBD and CDThere is a growing body of evidence that RBD can be successfully treated bymaintenance medication, although there is not one treatment study that hasrecruited RBD subjects by diagnostic criteria for a controlled trial. Recent methodologicaladvances (Post et al., 1998; Pezawas et al., 2002a), together with published