Ultradian rapid cycling in prepubertal and early adolescent bipolarity is not in transmission disequilibrium with Val/Met COMT alleles

Background: Prepubertal children and early adolescents with bipolar disorde rs (PEA-BP) who participate in the ongoing study "Phenomenology and Course of Pediatric Bipolar Disorders" have a high prevalence of ultradian (within 24-hour periods) rapid cycling. Based on a case-control ol finding reporte d in bipolar (BP) adults of art association between rapid and ultradian rap id cycling with the low-activity allele of catechol-O-methyltransferase (l- COMT), study of linkage and linkage disequilibrium of l-COMT in the PEA-BP population seemed warranted. Methods: Genotypes on a subset of the larger PEA-BP sample, for whom trio b lood collection was complete (i.e., probands and both of their biological p arents), were used to perform transmission disequilibrium? tests (TDTs). Di agnoses were established from a comprehensive battery that included WASH-U- KSADS (Washington University Kiddie Schedule for Affective Disorders and Sc hizophrenia) gh,en to both mothers and children and from consensus conferen ces. Probands with PEA-BP (N = 52) were 10.9 +/- 2.8 years old at index epi sode; had a mean age of BP onset at 8.0 +/- 3.8 years, were severely impair ed with a mean Children's Global Assessment Scale score of 44.5 +/- 8.9: an d manifested the cardinal features of BP (84.6% had euphoric mood, 76.9% ha d grandiosity, and 57.7% had psychosis). Ultradian rapid cycling occurred i n 75%. Genotyping of the single nucleotide polymorphism at COMT was perform ed using automated capillary electrophoresis single-strand conformational p olymorphism with detection by laser-induced fluorescence. Results: Transmission disequilibrium tests were not significant for prefere ntial transmission of l-COMT for the ultradian rapid-cycling subgroup or fo r the entire PEA-BP sample. Conclusions: The lack of linkage disequilibrium between l-COMT and ultradia n rapid cycling in the PEA-BP sample compared to reported findings of an as sociation in case-control studies of adults is discussed iii terms of age-s pecific developmentally relevant phenotypes, anticipatory mechanisms, and h eterogeneity. Repeat TDT analyses after these PEA-BP probands reach their a dult phenotypes will be informative. (C) 2000 Society of Biological Psychia try.