ORGANIC MENTAL RETARDATION--FAMILIAL AND GENETIC INFLUENCES

这个项目延伸了一个长期的精神发育迟滞研究， 这个项目的行为表型的各种遗传 综合征具体而言，该项目衡量了 精神病理学和心理社会，遗传和家族特征， Prader-Willi综合征、威廉姆斯综合征和唐氏综合征，以及对照组。 这些特征在一项连续的研究中进行了检查， 安慰剂对照药物治疗研究。我们选择普拉德-威利 威廉姆斯和唐氏综合征的研究，因为他们的新关系 在这个项目中的其他疾病;他们的分子遗传学 特征和承诺的基因行为的理解;和他们的 引人注目的临床特征。 在这个项目中有三个总体假设：（1）综合征 地位使智力迟钝者倾向于特定类型 精神病理学的特征，以及这些特征在 发展过程;（2）在表达的证内变异性 可能与分子遗传特征有关 以及社会心理、发展和家庭因素 从完善的双重诊断模型;和（3）药物治疗 使用降钙素摄取抑制剂可以减轻 与Prader-Willi综合征相关的精神病理学，包括 强迫症、强迫症和情感特征。 研究结果将整合行为和生物学方法， 精神发育迟滞研究;基因型-表型的进展 关系;并为新的行为和药理学 基于特定综合征的优势、劣势 和发展轨迹。

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.