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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH092377-03
Application #
8309367
Study Section
Behavioral Genetics and Epidemiology Study Section (BGES)
Program Officer
Garvey, Marjorie A
Project Start
2010-09-30
Project End
2015-04-30
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
3
Fiscal Year
2012
Total Cost
$680,540
Indirect Cost
$209,420
Name
Michigan State University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824
Suisman, Jessica L; Thompson, J Kevin; Keel, Pamela K et al. (2014) Genetic and environmental influences on thin-ideal internalization across puberty and preadolescent, adolescent, and young adult development. Int J Eat Disord 47:773-83
Racine, S E; Culbert, K M; Burt, S A et al. (2014) Advanced paternal age at birth: phenotypic and etiologic associations with eating pathology in offspring. Psychol Med 44:1029-41
Burt, S Alexandra; Klump, Kelly L (2013) The Michigan State University Twin Registry (MSUTR): an update. Twin Res Hum Genet 16:344-50
Culbert, Kristen M; Breedlove, S Marc; Sisk, Cheryl L et al. (2013) The emergence of sex differences in risk for disordered eating attitudes during puberty: a role for prenatal testosterone exposure. J Abnorm Psychol 122:420-32
Klump, Kelly L (2013) Puberty as a critical risk period for eating disorders: a review of human and animal studies. Horm Behav 64:399-410
Klump, K L; Culbert, K M; Slane, J D et al. (2012) The effects of puberty on genetic risk for disordered eating: evidence for a sex difference. Psychol Med 42:627-37