A Twin Study of Androgen Effects on Binge Eating Risk during Puberty in Males

项目总结 暴饮暴食(BE)发生在大多数饮食障碍中，在社区中发生的比例很高，包括在 儿童和青少年。BE的慢性病程和显著的精神和医学发病率进一步 证明了它对公共卫生的重要性。关键的是，尽管男性占BE病例的一半，但也有 探索男性勃起功能障碍风险的研究很少，而探索生物因素的研究几乎不是 存在。肾上腺和性腺雄激素是一组男性特有的生物因素，可能是至关重要的。 考虑到它们促进了男性的性别分化和青春期发育，它们导致了可口性的变化 动物的食物摄入量，它们是神经生物学系统内基因转录的有力调节器 与此相关。此外，动物研究和我们的初步人类数据表明，较低水平的雄激素 (例如，睾酮)预示着BE的表型水平更高，对Be in的遗传影响更强 男性在青春期，但还没有大规模的研究来检验这些生物学过程。更大规模的研究 它跨越青春期成熟的全过程(例如，肾上腺原基到性腺原基)，并全面 评估肾上腺和性腺雄激素是必要的下一步，将增强科学严谨性和 提供关键的可重复性和可翻译数据。拟议工作的长期目标是 确定雄激素对青春期男孩BE的表型和遗传风险的作用。具体目标 是为了：1)检查较低水平的肾上腺和/或性腺雄激素是否有助于在 青春期；以及2)检查遗传因素是否是驱动肾上腺和 青春期男孩体内存在性腺激素。参与者将包括1000名同性双胞胎男性(7岁- 17)通过密歇根州立大学双胞胎登记处招聘。调查问卷和访谈将是 对双胞胎和至少一位父母实施以评估BE、其他情绪/行为症状(例如，情绪， 焦虑)，以及青春期的身体变化。唾液样本将被收集和化验肾上腺和 性腺雄激素水平。将使用多水平结构方程模型来检验表型效应 在青春期肾上腺和性腺雄激素对BE的影响。潜在的孪生慢化模型将检验 较低的肾上腺和性腺雄激素水平与较强的遗传效应有关的程度 处于青春期。所有分析还将探索观察到的影响是否独立于其他因素 (例如，肥胖、焦虑、抑郁)在青春期发生变化，并与雄激素和BE有关。 我们的创新、多方法项目的发现有可能显著增加对 通过确定雄激素是导致男童BE的新的神经生物学因素，来研究男童BE的原因。 对男孩BE病因机制的更深入了解将缩小对推测的神经生物学的搜索范围 系统和基因，并有助于改善这些综合症的治疗和预防。

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.