ANDROGEN EFFECTS ON COGNITION IN TURNER SYNDROME

雌激素和雄激素似乎影响青春期女性的脑功能。环境和文化因素与雌激素和雄激素对大脑的生物学效应相互作用，从而影响认知和行为。患有特纳综合征的女性在青春期前或青春期时卵巢发育不良，不产生雌激素或雄激素。因此，特纳综合征代表了一个独特的，性功能缺陷，模型中，研究雄激素对认知和行为的生物学效应。这项建议是对先前资助的雄激素对青少年认知和行为影响的研究的延续、扩展和加强。研究组包括（1）两个特纳综合征组（10-14岁）：（A）雄激素组和（B）无雄激素组，以及（2）年龄匹配的正常女性对照组。在本次竞争性更新申请中，我们建议扩展原始纵向设计，对每例受试者进行为期4年的雄激素（或安慰剂）治疗随访。该项目的具体目的是：1）检查4年雄激素治疗对生长激素治疗的特纳综合征女孩的认知和心理调节的影响; 2）记录青春期特纳综合征女孩（接受或未接受雄激素治疗）与年龄和VIQ匹配的正常女孩之间认知和行为功能的差异和相似性，纵向随访4年。具体而言，我们假设：（1）接受雄激素治疗的女孩在视觉空间能力和视觉运动能力测试中表现更好（在最初的建议中假设），并注意（新假设），与未接受雄激素治疗的女孩相比，（2）雄激素治疗对视觉空间、视觉运动能力和注意力测试的影响将在1、2、3后逐渐增加，治疗4年后，Turner综合征和对照组女孩在这些方面的差异较小，（3）与未接受雄激素治疗的Turner综合征女孩相比，接受雄激素治疗的Turner综合征女孩在社会功能、情绪、运动功能或处理速度（语言和非语言）测试中的表现没有差异。这项对青少年认知和社会发展的持续研究是理解正常大脑发育的重要一步。此外，这些数据将有助于确定如何优化特纳综合征的认知功能，并将扩展男性/女性认知二型性机制的知识。

Estrogen and androgen appear to influence brain function in females at puberty. Environmental and cultural factors interact with the biological effects of estrogen and androgen on the brain and consequently on cognition and behavior. Women with Turner syndrome have dysgenetic ovaries that do not produce estrogen or androgen, before or at puberty. Therefore, Turner syndrome represents a unique, sex hormone-deficient, model in which to study the biological effects of androgen on cognition and behavior. This proposal is a continuation, expansion, and enhancement of the previously funded study of the effect of androgen on adolescent cognition and behavior. Study groups include (1) two Turner syndrome groups (ages 10-14): (A) androgen and (B) no androgen and (2) an age-matched, normal female control group. In this competitive renewal submission, we propose to extend the original longitudinal design by following each subject for a total of 4 years of androgen (or placebo) treatment. The specific aims of this project are to: 1) examine the effects of 4 years of androgen treatment of cognition and psychological adjustment in growth hormone-treated girls with Turner syndrome and 2) document the differences and similarities in cognitive and behavioral function between adolescent Turner syndrome girls (treated or not treated with androgen) and age- and VIQ-matched normal girls, followed longitudinally for 4 years. Specifically, we hypothesize that: (1) Girls treated with androgen will perform better on tests of visual spatial ability and visual-motor ability (hypothesized in initial proposal), and attention (new hypothesis), compared to the girls not treated with androgen, (2) The androgen treatment effects on tests of visual-spatial, visual-motor ability, and attention will incrementally increase after 1,2,3, and 4 years' treatment, resulting in fewer differences in these areas between Turner syndrome and control girls after 4 years, and (3) girls with Turner syndrome treated with androgen will not perform differently on tests of social function, mood, motor function, or processing speed (verbal and non-verbal), compared to girls with Turner syndrome not treated with androgen. This proposed continuing investigation of adolescent cognitive and social development represents an important step in understanding normal brain development. In addition, these data will help determine how to optimize cognitive function in Turner syndrome, and will extend knowledge of the mechanisms of male/female cognitive dimorphisms.