ANDROGEN EFFECTS ON COGNITION IN TURNER SYNDROME

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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.