2002 |
Klump, Kelly L. |
R03Activity Code Description: To provide research support specifically limited in time and amount for studies in categorical program areas. Small grants provide flexibility for initiating studies which are generally for preliminary short-term projects and are non-renewable. |
Familial Transmission of Eating Pathology &Sex Hormones @ Michigan State University
Anorexia and bulimia nervosa are often chronic disorders with some of the highest mortality rates (.10%) of any psychiatric illness. Greater understanding of the etiology of disordered eating attitudes and behaviors that underlie these sometimes fatal disorders will inform intervention and prevention efforts aimed at their amelioration. The primary purpose of the proposed study is to examine the etiology significance of ovarian hormones in the development of eating attitudes and behaviors by examining phenotypic and genetic relationships between eating pathology and basal estrogen and progesterone levels in a community-based sample of twins. A secondary aim is to examine phenotypic and genetic relationships between the stress hormone cortisol and disordered eating variables. Estrogen is expected to show positive relationships with dietary restraint, weight preoccupation, and eating/weight./body concerns, and negative associations with binge eating and compensatory behaviors. Progesterone is expected to attenuate these relationships, such that lower estrogen: progesterone ratios will be associated with increased binge eating and compensatory behaviors, and decreased dietary restraint and associated attitudes. Cortisol is expected to show significant positive relationships with all forms of disordered eating. Common genetic factors are expected to contribute significantly to all of these hormone/disordered eating phenotypic relationships. Participants will include 50 female dizygotic twins recruited from the campus of Michigan State University and surrounding metropolitan areas who will complete self-report questionnaires assessing body dissatisfaction, weight preoccupation, binge eating, compensatory behaviors, eating concerns, and dietary restraint. Early follicular phase salivary hormone concentrations of estradiol, progesterone, and cortisol will be obtained between the hours of 0800 and 0900. Phenotypic associations between eating variables and hormone concentrations will be examined using within-person correlations whereas genetic associations will be examined via cross- twin, cross-trait correlations (i.e., Twin 1,s eating attitudes with Twin 2's hormone levels) and Cholesky Decomposition and model fitting analyses. Understanding the magnitude and nature of genetic associations will increase understanding of the etiology of eating disorders and lead to the potential identification of endogenous risk factors to be explored in genetic and neurobiological research.
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1 |
2002 — 2003 |
Klump, Kelly L. |
R03Activity Code Description: To provide research support specifically limited in time and amount for studies in categorical program areas. Small grants provide flexibility for initiating studies which are generally for preliminary short-term projects and are non-renewable. |
Genetic and Environmental Risk For Eating Disorders @ Michigan State University
DESCRIPTION (provided by applicant): The eating disorders anorexia nervosa and bulimia nervosa have some of the highest mortality rates (i.e., > 10 percent) of any psychiatric illness. The overall purpose of the proposed study is to increase understanding of the epidemiology of these disorders by examining genetic and environmental risk factors using a developmental, behavioral genetic approach. Data for this project come from 680 11 year-old twins participating in the population-based, longitudinal Minnesota Twin Family Study. Twins from this larger project were assessed at three-year intervals following baseline (i.e., ages 11, 14, 17), and data from all three timepoints will be used in analyses. The first aim of the proposed study is to examine developmental differences in genetic and environmental influences on disordered eating attitudes and behaviors across adolescence (i.e. at ages 11, 14, and 17). It is hypothesized that genetic influences will increase and environmental influences will decrease in magnitude across these three adolescent ages. The second aim is to determine the role of puberty in these developmental differences. It is hypothesized that eating pathology will show negligible genetic influence in pre-pubertal twins, but significant genetic effects in post-pubertal twins. Structural equation modeling will be used to examine each of these first two hypotheses. The final aim of the proposed project is to identify specific genetic and environmental risk factors for eating disorders by examining Time 1 (age 11) psychiatric (depression, anxiety, and disordered eating), temperamental (negative emotionality, positive emotionality, and constraint), physical/maturational (body mass index (BMI), pubertal status), and family (relationships with parents, marital discord) predictors of Time 3 (age 17) eating disorder status. The nature (i.e., genetic versus environmental) of significant risk factors will then be examined. It is hypothesized that anxiety disorders, negative emotionality, pubertal status, and BMI will be the most significant predictors of eating pathology. Further, risk factor/eating disorder covariations are hypothesized to be due to common genetic rather than common environmental factors. These last hypotheses will be tested using logistic regression analyses as well as structural equation modeling. Findings from this study will significantly increase understanding of developmental risk factors for eating disorders and potentially inform intervention and prevention efforts aimed at their amelioration.
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1 |
2008 — 2012 |
Klump, Kelly L. |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
A Twin Study of Ovarian Hormones and Disordered Eating @ Michigan State University
DESCRIPTION (provided by applicant): This application is in response to PA-07-126 "Women's Mental Health and Sex/Gender Differences Research." The PA calls for studies of neurobiological, sex hormone, and genetic factors contributing to sex differences in the prevalence and etiology of mental disorders. Bulimic syndromes are much more prevalent in women than men and may exhibit genetic influence only after sex hormone activation. The long-term objective of this project therefore is to identify a novel set of neurobiological mechanisms that contribute to genetic influences on bulimic syndromes in women. The specific aims are to examine: 1) phenotypic relationships between changes in ovarian hormone levels and changes in disordered eating across the menstrual cycle in a large sample of female twins;and 2) whether a common set of genetic factors underlie associations between ovarian hormones and binge eating. Participants will include 590 same-sex female twins recruited through birth records in Michigan. Structured clinical interviews will be administered to assess eating disorders and other Axis I disorders. Daily salivary hormone samples and behavioral measures of binge eating and mood symptoms will be collected for 45 days. Radioimmunoassay will be used to analyze estradiol, and enzymeimmunoassay will be used to analyze progesterone. Dynamical systems models will examine the extent to which changes in ovarian hormones predict changes in binge eating across the menstrual cycle. Genetic mediation of these phenotypic associations will be examined by incorporating twin pair information into analyses using bivariate and multivariate genetic models. The proposed set of studies follow recommendations of Becker et al. (2005) to use naturalistic, longitudinal studies across the menstrual cycle to establish associations between ovarian hormones and binge eating before attempting experimental designs in humans. We propose to extend this approach by examining whether these naturalistic associations have a genetic component. Findings from our multi-method studies have the potential to significantly increase understanding of the causes of bulimic syndromes in women by seeking the underlying neurobiological mechanisms contributing to their genetic diathesis. 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: Bulimic syndromes are significant mental health problems that preferentially afflict late adolescent and young adult women. The pronounced psychiatric and medical morbidity associated with these disorders underscore their public health significance and the need to understand their development. Greater insight into neurobiological mechanisms will narrow the search for candidate genes and contribute to improved treatment and prevention of these disorders.
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1 |
2010 — 2014 |
Klump, Kelly L. |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
The Effects of Estradiol On Genetic Risk For Disordered Eating During Puberty @ Michigan State University
DESCRIPTION (provided by applicant): 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.
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1 |
2017 — 2021 |
Klump, Kelly L |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
A Twin Study of Exogenous Hormone Exposure and Risk For Binge Eating @ Michigan State University
PROJECT SUMMARY Extant animal and human data show that ovarian hormones are critical neurobiological risk factors for binge eating in women. Natural increases in these hormones across the menstrual cycle substantially increase risk for binge eating via hormonally induced increases in genetic risk. These data have significantly advanced etiological models and our understanding of the female predominance in eating disorder risk. However, this increased knowledge comes with an urgent public health responsibility. In the US today, 1 in 3 women take contraceptives that contain combinations of hormones that mimic the riskiest milieus for binge eating (i.e., combined oral contraceptives (COCs) containing both estrogen and progesterone).The relatively commonplace prescription of COCs may substantially increase risk for binge eating in women, particularly in those who are genetically vulnerable to eating disorders. This possibility underscores the urgent need to examine COC effects on binge eating to inform women's health practices and avert a potentially dangerous (and chronic) path toward eating disorders in unsuspecting young women. The goal of the proposed project is to use a multi- method (behavioral genetic, neuroendocrine), longitudinal twin study to document the effects of COCs on phenotypic and genetic risk for binge eating in women. If COCs increase phenotypic risk for binge eating in women, then there should be significantly higher rates of binge eating in twins using COCs than their non- using co-twins (a population-level, between-subject effect) and substantial increases in binge eating when COC users transition from inactive to active pills (an individual-level, within-subject effect). Moreover, if COCs influence binge eating through genetic mechanisms, then there should be significantly increased genetic risk in twins taking COCs (a population-level, between-subject effect) and substantial increases in genetic effects when COC users transition from inactive to active pills (an individual-level, within-subject effect). We will examine all of these hypotheses in a large sample of female twins (N = 1,000) assessed daily for 45 days using multiple measures of binge eating and related phenotypes. Notably, the proposed project would directly address NIH directives to enhance Rigor and Reproducibility through its validation of cross-sectional findings (e.g., increased binge eating in COC twins vs. their non-using co-twins) with longitudinal data (i.e., increased binge eating when transitioning from inactive to active pills) within a twin study design that substantially minimizes confounders and selection factors into COC use. The inferential power gained from these multi-level analyses has the potential to significantly advance public health policy and necessitate a re-thinking of basic assumptions about COC prescriptions and use. The clinical implications of our findings run the gamut from requiring physicians to screen for personal and family histories of eating disorders (an uncommon practice) to the selection of alternative contraceptives that are less risky for women.
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1 |
2019 — 2021 |
Culbert, Kristen Klump, Kelly L |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
A Twin Study of Androgen Effects On Binge Eating Risk During Puberty in Males @ Michigan State University
PROJECT SUMMARY Binge eating (BE) occurs in most eating disorders and at significant rates in the community, including among children and adolescents. The chronic course of BE and significant psychiatric and medical morbidity further attest to its public health significance. Critically, although males account for up to one-half of BE cases, there is a paucity of research exploring risk for BE in males and studies exploring biological factors are nearly non- existent. Adrenal and gonadal androgens are one set of male-specific biological factors that may be critical given that they drive sexual differentiation and pubertal development in males, they cause changes in palatable food intake in animals, and they are potent regulators of gene transcription within neurobiological systems relevant to BE. Moreover, animal studies and our preliminary human data show that lower levels of androgens (e.g., testosterone) are predictive of higher phenotypic levels of BE and stronger genetic influences on BE in males during puberty, but no large-scale study has examined these biological processes. Larger-scale studies that span the full range of pubertal maturation (e.g., adrenarche through gonadarche) and comprehensively assess adrenal and gonadal androgens are a necessary next step that will enhance scientific Rigor and provide critical Reproducibility and translational data. The long-term objective of the proposed work is to identify the role of androgens on phenotypic and genetic risk for BE in boys during puberty. The Specific Aims are to: 1) examine whether lower levels of adrenal and/or gonadal androgens contribute to BE in boys during puberty; and 2) examine if genetic factors are mechanisms that drive phenotypic effects of adrenal and gonadal androgens on BE in boys during puberty. Participants will include 1,000 same-sex male twins (ages 7- 17) recruited through the Michigan State University Twin Registry. Questionnaires and interviews will be administered to the twins and at least one parent to assess BE, other mood/behavioral symptoms (e.g., mood, anxiety), and the physical changes of puberty. Salivary samples will be collected and assayed for adrenal and gonadal androgen levels. Multilevel structural equation models will be used to examine the phenotypic effects of adrenal and gonadal androgens on BE during puberty. Latent twin moderation models will examine the extent to which lower levels of adrenal and gonadal androgens are associated with stronger genetic effects on BE during puberty. All analyses will also explore whether observed effects are independent of other factors (i.e., adiposity, anxiety, depression) that change during puberty and are associated with androgens and BE. Findings from our innovative, multi-method project have the potential to significantly increase understanding of the causes of BE in boys by identifying androgens as novel neurobiological factors that contribute to BE. Greater insight into etiological mechanisms of BE in boys will narrow the search for putative neurobiological systems and genes and contribute to improved treatment and prevention of these syndromes.
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1 |
2021 |
Klump, Kelly L |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Administrative Supplement: a Twin Study of Exogenous Hormone Exposure and Risk For Binge Eating @ Michigan State University
PROJECT SUMMARY Extant animal and human data show that ovarian hormones are critical neurobiological risk factors for binge eating in women. Natural increases in these hormones across the menstrual cycle substantially increase risk for binge eating via hormonally induced increases in genetic risk. These data have significantly advanced etiological models and our understanding of the female predominance in eating disorder risk. However, this increased knowledge comes with an urgent public health responsibility. In the US today, 1 in 3 women take contraceptives that contain combinations of hormones that mimic the riskiest milieus for binge eating (i.e., combined oral contraceptives (COCs) containing both estrogen and progesterone).The relatively commonplace prescription of COCs may substantially increase risk for binge eating in women, particularly in those who are genetically vulnerable to eating disorders. This possibility underscores the urgent need to examine COC effects on binge eating to inform women's health practices and avert a potentially dangerous (and chronic) path toward eating disorders in unsuspecting young women. The goal of the proposed project is to use a multi- method (behavioral genetic, neuroendocrine), longitudinal twin study to document the effects of COCs on phenotypic and genetic risk for binge eating in women. If COCs increase phenotypic risk for binge eating in women, then there should be significantly higher rates of binge eating in twins using COCs than their non- using co-twins (a population-level, between-subject effect) and substantial increases in binge eating when COC users transition from inactive to active pills (an individual-level, within-subject effect). Moreover, if COCs influence binge eating through genetic mechanisms, then there should be significantly increased genetic risk in twins taking COCs (a population-level, between-subject effect) and substantial increases in genetic effects when COC users transition from inactive to active pills (an individual-level, within-subject effect). We will examine all of these hypotheses in a large sample of female twins (N = 1,000) assessed daily for 49 days using multiple measures of binge eating and related phenotypes. Notably, the proposed project would directly address NIH directives to enhance Rigor and Reproducibility through its validation of cross-sectional findings (e.g., increased binge eating in COC twins vs. their non-using co-twins) with longitudinal data (i.e., increased binge eating when transitioning from inactive to active pills) within a twin study design that substantially minimizes confounders and selection factors into COC use. The inferential power gained from these multi-level analyses has the potential to significantly advance public health policy and necessitate a re-thinking of basic assumptions about COC prescriptions and use. The clinical implications of our findings run the gamut from requiring physicians to screen for personal and family histories of eating disorders (an uncommon practice) to the selection of alternative contraceptives that are less risky for women.
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1 |