Timing of puberty is an important issue in healthy psychosocial of adolescents. It is unfortunate that an """"""""off-time"""""""" group of children, like those with premature adrenarche (PA), have not been included in studies of puberty noted by rising adrenal androgen concentrations. Increasing adrenal androgens are responsible for physical manifestations of puberty (e.g., sexual hair). When such development occurs prior to age 8 in girls and 9 + in boys, it is considered premature. Pilot study show higher hormone concentrations, an increased incidence of anxiety, depression and externalizing behavior problems, cognitive differences, and heightened cortisol reactivity in PA compared to on-time children. In examining genetic variation, 35% of children with PA also are heterozygous carriers of mutations in the 21-hydroxylase gene. Carriers are also more cortisol reactive. No studies have examined whether individual genetic variation may moderate the endocrine milieu in PA children, and in turn, alter the likelihood of emotional and behavior problems or cognitive difficulties.
The aims of study are to: (1) compare differences in the hormone milieu (gonadal and adrenal hormones, cortisol reactivity), genetic variation associated with hyperandrogenism [mutation of CYP21 or glucocorticoid receptor, (GCR)], adjustment (anxiety, depression and externalizing behavior problems), and cognitive functioning (standardized IQ tests and memory) in PA and on-time adrenarche girls; (2) examine the mediated moderation of PA by individual genetic variation (mutation of CYP21 or GCR) on child adjustment (anxiety, depression and externalizing behavior problems) and cognitive function (standardized IQ tests and memory). This moderation effect is indirect and mediated through the hormone milieu. The sample will consist of 90, 6-to-8 year- old PA girls from pediatric endocrine clinics and 90 matched on time adrenarche girls. Measures include hormone concentrations, stage of puberty, cortisol reactivity, genetic variation, psychological variables, and IQ tests and memory. Information may lead to prevention/intervention efforts to reduce emotional and behavior problems and cognitive difficulties in children with PA.
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