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

265 Comorbidity in mixed states and rapid-cycling disordersseveral studies have not been able to support the idea that rapid cycling is related tothyroid dysfunction (Joffe et al., 1988; Post et al., 1989; Bartalena et al., 1990),including a large study of almost 500 bipolar affective patients (Kupka et al., 2002).However, there are reports in favor of this possibility (Extein et al., 1982; Cowdryet al., 1983; Bauer et al., 1990; Oomen et al., 1996). Therefore, a higher frequency ofco-occurring thyroid dysfunction has neither been proven nor ruled out for eithermixed or rapid-cycling bipolar affective disorders, although some indications ofsuch a relationship may exist. Mood-stabilizing medication, especially lithium,may affect the thyroid axis and complicate such analyses, as most bipolar affectivepatients will have previously received a mood stabilizer.A report on a series of 13 patients with epilepsy and manic episodes (Kudo et al.,2001) showed that, compared to bipolar affective controls, the patients withepilepsy and mania had less severe manic and depressive episodes. Interestingly,the majority of the patients with mania and epilepsy (8 out of 13) had a rapidcyclingcourse pattern with regard to mood episodes. Although there is no cleargeneral estimate concerning the frequency of manic episodes in epilepsy, temporallobe epilepsy has been reported to be among the leading causes of organic bipolaraffective disorder (Rundell and Wise, 1989). Additionally, the etiological relationshipbetween epilepsy and manic episodes is not clear. Rapid-cycling bipolardisorder has also been reported in a series of five patients with primary idiopathicdystonia (Lauterbach et al., 1992).Rapid cycling has been reported in various other neuropsychiatric disorders,such as head injury (Zwil et al., 1993), stroke (Berthier, 1992), learning disability(Jan et al., 1994; Raghavan et al., 1995), or rarer illnesses, such as cerebralsarcoidosis (Walbridge, 1990) or tuberous sclerosis (Hagenah et al., 1999). Formixed bipolar affective disorders, we are only aware of one report of a mixedbipolar affective episode following head injury (Bamrah and Johnson, 1991).Overall, one must be careful to equate such cases of rapid cycling in organicbrain disease with ‘‘idiopathic’’ rapid cycling in bipolar affective disorder concerningsymptomatic presentation. Instead, in some reports, the symptomatologyseems to be ‘‘very atypical’’ and would not necessarily meet DSM-IV criteria forbipolar affective disorder. Nevertheless, in organic brain disease, rapid-cycling-likesyndromes may be either more frequent than mixed bipolar affective episodes ormore often noticed by clinicians, as they may have a higher relevance for acutetreatment (i.e., the treatment could become longer or more complicated). In somecases, the fluctuating course of organic brain disease might mimic rapid-cyclingforms (or even mixed states) in bipolar affective disorders.Although it has been discussed that patients with mixed bipolar affectivedisorders may show more neuropsychological impairment than other bipolaraffective patients, no such evidence was shown in a recent empirical study