ORGANIC MENTAL RETARDATION--FAMILIAL AND GENETIC INFLUENCES

这个项目扩展了一系列关于智力低下的研究 这个项目是关于不同遗传基因的行为表型 综合症。具体地说，该项目衡量了 精神病理学和心理社会、遗传和家庭特征 Prader-Willi、Williams和Down综合征，并设对照组。 这些特征在一项纵向顺序研究中得到了检验 安慰剂对照药物治疗研究。我们选择普莱德-威利， 威廉姆斯综合征和唐氏综合征因其关系新颖而值得研究 该计划项目中的其他疾病；它们的分子遗传学 基因行为理解的特点和前景；及其 引人注目的临床特征。 在这个项目中有三个最重要的假设：(1)综合征 地位使智力低下的人倾向于特定的类型 以及这些特征在过去几年中的显著变化 发展历程；(2)证内表达的变异性 精神病的发生可能与分子遗传特征有关 以及来自心理社会、发展和家庭的因素 来自公认的双重诊断模型；以及(3)药物治疗 使用5-羟色胺摄取抑制剂可以缓解 与Prader-Willi综合征有关的精神病理学，包括 强迫症、强迫症和情绪化特征。 研究结果将把行为学和生物学方法结合起来 智力低下的研究；关于基因-表型的高级知识 关系；并为新的行为和药理学铺平道路 基于特定症状的优势、劣势的干预措施 和发育轨迹。

This project extends a long line of mental retardation research within this Program Project on the behavioral phenotypes of various genetic syndromes. Specifically, this Project measures the development of psychopathology and psychosocial, genetic, and familial features in Prader-Willi, Williams and Down syndromes, and in a comparison group. these features are examined in a longitudinal-sequential study with placebo-controlled pharmacotherapy studies. We select Prader-Willi, Williams and Down syndromes for study because of their novel relations to other disorders in this Program Project; their molecular genetic characteristics and promise for gene-behavior understandings; and their compelling clinical features. There are three, overarching hypotheses in this project: (1) syndromic status predisposes persons with mental retardation to particular types of psychopathology and to distinctive shifts in these features over the course of development; (2) within-syndrome variability in the expression of psychopathology is likely associated with molecular genetic features as well as with psychosocial, developmental, and familial factors derived from well-established models of dual diagnosis; and (3) pharmacotherapy using serotonin-uptake inhibitors can alleviate symptom expression of psychopathology associated with Prader-Willi syndrome, including obsessive, compulsive and affective features. Findings will integrate the behavioral and biological approaches to research in mental retardation; advance knowledge of genotype-phenotype relations; and pave the way for novel behavioral and pharmacologic interventions that are based on syndrome-specific strengths, weaknesses and developmental trajectories.