Eating disorders are significant mental health problems that affect over 5 million women in the United States. Collectively, they are associated with the highest mortality rates of any psychiatric disorder and tend to have chronic courses characterized by significant psychiatric and medical morbidity. They display a stereotypic pattern of development in girls with significant increases in prevalence only after puberty. Theories accounting for this pubertal risk have focused almost entirely on psychosocial risk factors that increase during puberty and may contribute to risk in girls. However, recent data confirm that genetic factors are critically important as well, as the heritability of disordered eating increases dramatically across puberty (from 0 percent in pre-puberty to e50 percent in post-puberty). To date, no studies have examined factors underlying pubertal "activation" of genetic effects. Increases in estradiol during puberty may account for these effects, as estradiol drives pubertal changes in girls and is a potent regulator of gene transcription within neurobiological systems implicated in eating disorders. The long-term objective of the proposed work is to identify the role of estradiol in genetic risk for disordered eating during puberty in girls.
The Specific Aims are to examine: 1) whether estradiol increases or "moderates" genetic influences on disordered eating in girls during puberty;and 2) if estradiol's effects are independent of other factors (i.e., progesterone, luteinizing hormone, follicle stimulating hormone, physical changes of puberty, body weight and adiposity) that change during puberty. Participants will include an "enriched" sample of 1,000 same-sex female twins between the ages of 9 and 14 recruited through the Michigan State University Twin Registry. Approximately 30 percent of the sample will be selected to exhibit elevated disordered eating. Questionnaires and interviews will be administered to each twin and at least one parent to assess disordered eating symptoms and the physical changes of puberty. Body mass index and bioelectric impedence analysis will be used to assess body mass index and adiposity, respectively. Salivary and serum samples will be collected and assayed for hormone levels using standard enzyme immunoassay techniques. Latent gene x environment twin models will examine the extent to which estradiol moderates genetic influences on disordered eating and whether these effects are independent of other factors that change during puberty. Findings from our innovative, multi-method studies have the potential to significantly increase understanding of the causes of eating disorders by seeking underlying neurobiological mechanisms contributing to their genetic diathesis during puberty. Greater insight into etiological mechanisms will narrow the search for candidate genes and contribute to improved treatment and prevention of these disorders.
Eating disorders are significant mental health problems that increase in prevalence only after puberty in girls. Emerging data suggest that increased risk may be due to the activation of genes for eating disorders during puberty. Greater insight into neurobiological factors that contribute to these genetic effects will narrow the search for candidate genes and ultimately contribute to improved treatment and prevention of these disorders.
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