Geller B, Cook E H
Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Biol Psychiatry. 2000 Apr 1;47(7):605-9. doi: 10.1016/s0006-3223(99)00251-6.
Prepubertal children and early adolescents with bipolar disorders (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 finding reported in bipolar (BP) adults of an association between rapid and ultradian rapid 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.
Genotypes on a subset of the larger PEA-BP sample, for whom trio blood collection was complete (i. e., probands and both of their biological parents), were used to perform transmission disequilibrium tests (TDTs). Diagnoses were established from a comprehensive battery that included WASH-U-KSADS (Washington University Kiddie Schedule for Affective Disorders and Schizophrenia) given to both mothers and children and from consensus conferences. Probands with PEA-BP (N = 52) were 10.9 +/- 2.8 years old at index episode; had a mean age of BP onset at 8.0 +/- 3.8 years; were severely impaired, with a mean Children's Global Assessment Scale score of 44.5 +/- 8.9; and manifested the cardinal features of BP (84.6% had euphoric mood, 76.9% had grandiosity, and 57.7% had psychosis). Ultradian rapid cycling occurred in 75%. Genotyping of the single nucleotide polymorphism at COMT was performed using automated capillary electrophoresis single-strand conformational polymorphism with detection by laser-induced fluorescence.
Transmission disequilibrium tests were not significant for preferential transmission of l-COMT for the ultradian rapid-cycling subgroup or for the entire PEA-BP sample.
The lack of linkage disequilibrium between l-COMT and ultradian rapid cycling in the PEA-BP sample compared to reported findings of an association in case-control studies of adults is discussed in terms of age-specific developmentally relevant phenotypes, anticipatory mechanisms, and heterogeneity. Repeat TDT analyses after these PEA-BP probands reach their adult phenotypes will be informative.
参与正在进行的“儿童双相情感障碍的现象学与病程”研究的青春期前儿童和青少年双相情感障碍患者（PEA - BP）超日节律（24小时内）快速循环的患病率很高。基于双相情感障碍（BP）成年患者中一项病例对照研究报告的快速循环和超日节律快速循环与儿茶酚 - O - 甲基转移酶低活性等位基因（l - COMT）之间的关联，对PEA - BP人群中l - COMT的连锁和连锁不平衡进行研究似乎是必要的。
对较大的PEA - BP样本中的一个子集进行基因分型，该子集的三联体血液采集已完成（即先证者及其双亲），用于进行传递不平衡检验（TDT）。诊断由一套综合测评确定，包括对母亲和儿童进行的华盛顿大学儿童情感障碍与精神分裂症评定量表（WASH - U - KSADS）以及共识会议。PEA - BP先证者（N = 52）在首次发作时年龄为10.9±2.8岁；双相情感障碍发病的平均年龄为8.0±3.8岁；严重受损，儿童总体评定量表平均得分为44.5±8.9；表现出双相情感障碍的主要特征（84.6%有欣快情绪，76.9%有夸大观念，57.7%有精神病性症状）。75%出现超日节律快速循环。使用自动毛细管电泳单链构象多态性结合激光诱导荧光检测对COMT的单核苷酸多态性进行基因分型。
对于超日节律快速循环亚组或整个PEA - BP样本，l - COMT的优先传递，传递不平衡检验无显著意义。
结合年龄特异性发育相关表型、预期机制和异质性，讨论了与成人病例对照研究中报道的关联结果相比，PEA - BP样本中l - COMT与超日节律快速循环之间缺乏连锁不平衡的情况。这些PEA - BP先证者达到成人表型后重复进行TDT分析将提供有价值的信息。
