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

28 A. Marneros and F. K. GoodwinAnother explanation delivered by the finding of Coryell et al.(1992) may derivefrom the assumption that a greater cyclicity seems to be frequently associated withfemales.Age at onsetAccording to the findings of Fujiwara et al. (1998), age at onset (for rapid-cyclingpatients) can be divided into early (onset at an age of 25 years and younger) and lateronset (onset at an age of 26 years or older). These data suggest that early- and late-onsetbipolar disorders are distinct illness subtypes with different courses and responsesto treatment (Calabrese et al., 2000). The Japanese authors concluded that patientswith an earlier onset tend to have rapid cycling at an early stage and a good responseto carbamazepine. Those with later onsets tended to have relatively long latency untilthe appearance of rapid cycling and a good response to lithium.Rapid cycling, as well as mixed states in childhood and adolescence, has notbeen investigated systematically, but some reports have shown that the prevalenceof these states in childhood and adolescence is not rare (Calabrese et al., 2000; seeChapter 10).Family studies and geneticsMost of the studies of the families of patients with rapid-cycling bipolar disordershow no difference between rapid- and non-rapid-cycling patients. That is, rapidcycling is not more frequent in families of patients with rapid cyclers (Nurnbergeret al., 1988; Coryell et al., 1992; Lish et al., 1993; Maj et al., 1994). Although thestudies mentioned appear to argue convincingly against any inheritance of rapidcycling in general, the less common form of early-onset rapid cycling may befamily-related (Calabrese et al., 2000). Studies reporting on genetic abnormalities(more or less anecdotal) are rare and should be replicated (Kilzieh and Akiskal,1999; Calabrese et al., 2000).Biological dataAlso uncertain are other biological correlations of rapid cycling, as described in thepresent book by Grunze and Walden (Chapter 14).ComorbidityThe issue of comorbidity as it relates to rapid cycling is complex. Calabrese et al.(2000) reviewed the extensive literature on thyroid dysfunction in patients withbipolar rapid cycling, noting that while many studies do report an associationbetween rapid cycling and reduced thyroid function, not every study confirmed it.Alcohol and drug abuse is another comorbid disorder that is frequently associatedwith the acceleration of remanifestations and rehospitalizations, but there is no