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

63 Rapid-cycling bipolar disorderPsychiatric patients with psychiatric illness in velocardiofacial syndrome (a geneticcondition caused by a microdeletion of chromosome 22q11, which includes theCOMT gene) were studied. Of 8 patients studied, 100% were found to haveCOMT met polymorphism on the complementary chromosome 22. It was hypothesizedthat, since the blockade of catecholamine reuptake by tricyclic antidepressantsand the blocking of breakdown by monoamine oxidase inhibitors have been associatedwith the induction of mania, homozygosity for COMT158 met predisposes torapid cycling, and possibly represents a risk factor in the use of antidepressants as well.This study examined the frequency of COMT 158 met in 60 rapid cyclers. Of the 60ultrarapid cyclers enrolled, four had been genotyped at the time of this publication,and all four were homozygous for COMT158 met (the low-activity allele), supportingthe hypothesis that the presence of this allelemayalterthecourseofbipolardisorder.In addition to the above-mentioned data, attempts to explore any geneticcorrelation with susceptibility to rapid-cycling bipolar disorder have continued(Jones and Craddock, 2001; Cusin et al., 2001). Some of the genes of particularinterest include those encoding the serotonin transporter, monoamine oxidaseA (MAOA) and COMT (Jones and Craddock, 2001). Cusin et al. (2001) reportedresults suggesting that the serotonin transporter gene-linked functional polymorphicregion (5-HTTLPR) variants may confer susceptibility toward rapidcyclingmood disorders. They retrospectively studied a sample of inpatientsaffected by recurrent and rapid-cycling mood disorders. The serotonin transportergene-linked functional polymorphic region (5-HTTLPR) and the (A218C) tryptophanhydroxylase (TPH) gene variant were determined using a polymerasechain reaction-based technique. For 5-HTTLPR polymorphism, they genotyped435 inpatients affected by major depressive (n ¼ 153), bipolar (n ¼ 213), andrapid-cycling (n ¼ 69) mood disorders and 456 controls. For TPH, they genotyped399 inpatients (mood disorder, n ¼ 132; bipolar, n ¼ 203; rapid-cycling, n ¼ 64)and 259 controls. Random regression model analysis was used to investigate thelongitudinal time course of the illness. It was found that 5-HTTLPR and TPHpolymorphisms were not associated with a mood-disorder time course. However,the researchers observed an excess of 5-HTTLPR* long alleles among rapid-cyclingsubjects compared with both controls (P ¼ 0.018) and remitting mood disorders(P ¼ 0.006). TPH frequencies did not differ between mood-disorder subtypes. Eventhough the results of this study were not definitive, the large sample of subjects lentit credibility. More studies are needed to duplicate or clarify these results.PathophysiologyFindings from neuroimaging studies continue to enrich our understanding of thepathophysiology of mood disorders generally and rapid-cycling bipolar disorder