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

68 O. Elhaj and J. R. Calabresepubertal maturation. The results of these naturalistic studies warrant furthercontrolled and longitudinal studies to provide more generalizable conclusionsabout the phenomenology of rapid-cycling bipolar disorder in children, and itsmanagement.In Calabrese et al.’s paper (2000a) contained in the preceding book, we reportedthe following with regard to comorbidity: extensive literature exists on the presenceof thyroid dysfunction in patients with bipolar rapid cycling. Some studiesdo (Cho et al., 1979; Cowdry et al., 1983; Bauer et al., 1990; Kusalic, 1992; McKeonet al., 1992) but most do not (Joffe et al., 1988; Nurnberg et al., 1988; Wehr et al.,1988; Bartalena et al., 1990; Coryell et al., 1992; Shen, 1992; Cole et al., 1993; Majet al., 1994; Oomen et al., 1996; Post et al., 1997) suggest that rapid cycling isassociated with an underlying thyroid abnormality. Usually (Khouzam et al.1991), the observed abnormality of thyroid dysfunction has been in the directionof decreased end-organ function. Herz (1964) first proposed that rhythmic disordersof mood might be caused by removal of the thyroid gland. Twenty-two recentlythyroidectomized patients were examined for evidence of psychiatric complicationsin Frederiksberg Hospital, Copenhagen, Denmark. Ten exhibited postsurgicalpsychiatric symptoms in the absence of any family psychiatric history. The authorsdescribed this as the ‘‘endocrine psycho-syndrome’’ and specifically noted that eightpatients exhibited temporary attacks of depression soon after the surgery.Cho et al. (1979) first demonstrated that the prevalence of lithium-inducedhypothyroidism was much higher in rapid cyclers (31%) than in non-rapid cyclers.This was replicated by Cowdry et al. (1983), who noted overt hypothyroidism in50.7% of 24 rapid cyclers and in none of 19 non-rapid cyclers. Elevated TSH levelswere present in 92% of the rapid cyclers and 32% of the non-rapid cyclers. Five yearslater, the same group (Wehr et al., 1988) refuted their earlier finding that thyroiddysfunction was no more common in rapid cyclers than in non-rapid cyclers. Baueret al. (1990) have carried out the most thorough examination of thyroid function,reporting a spectrum of thyroid abnormalities in rapid cycling. They have also beguna systematic examination of the potential mood-stabilizing properties of thyroidsupplementation, when used in augmentation of conventional mood stabilizers. Of30 patients with bipolar rapid cycling studied prospectively for the presence ofthyroid failure, 23% had grade I hypothyroidism (decreased FTIs with overt signsand symptoms), 27% had grade II (normal FTI, elevated TSH, and a single sign/symptom), and 10% had grade III (everything is normal, but there is an augmentedTSH response to thyroid-releasing hormone). A median and modal frequency of24 episodes/year with a maximal frequency of two episodes per day suggests thatepisode counting was done with criteria inconsistent with the DSM-IV.It is clear that there is an increase in the prevalence of alcohol and drug abuse inpatients with bipolar disorder (Regier et al., 1990). Whether rapid cyclers have an