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

雄激素对男性青春期暴食风险影响的双胞胎研究

• 批准号: 10115820
• 负责人: Kristen Culbert
• 金额: $ 67.28万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-15 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10115820
• 关键词: Address; Adolescent; Adrenal Glands; Affect; Age; Androgens; Animals; Anxiety; Behavioral Genetics; Behavioral Symptoms; Binge Eating; Biological; Biological Assay; Biological Factors; Biological Process; Child; Chronic; Communities; Consumption; Data; Development; Disease; Eating; Eating Disorders; Equation; Etiology; Fatty acid glycerol esters; Female; Fibrinogen; Food; Funding; Genes; Genetic; Genetic Risk; Genetic Transcription; Hormonal; Hormones; Institutes; Intake; Interview; Knowledge; Male Adolescents; Medical; Mental Depression; Mental Health; Methods; Michigan; Modeling; Moods; Morbidity - disease rate; Neurobiology; Obesity; Palate; Parents; Participant; Phenotype; Predisposition; Prevention; Process; Production; Psychopathology; Puberty; Public Health; Questionnaires; Registries; Regulator Genes; Reproducibility; Research; Risk; Risk Factors; Role; Same-sex; Sampling; Sex Differentiation; Structure; Syndrome; System; Testosterone; Treatment Effectiveness; Twin Multiple Birth; Twin Studies; United States National Institutes of Health; Universities; Work; animal data; base; boys; comorbidity; design; human data; improved; individualized prevention; innovation; insight; male; men; novel; personalized intervention; recruit; saliva sample; sample archive; secondary analysis; sex; success; sugar; therapy development

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.

项目概要 暴食 (BE) 发生在大多数饮食失调中，并且在社区中发生率很高，包括 儿童和青少年。 BE 的慢性病程以及显着的精神和医学发病率进一步 证明其对公共卫生的重要性。至关重要的是，尽管男性占 BE 病例的一半，但 探索男性 BE 风险的研究很少，而且探索生物因素的研究几乎是非 存在的。肾上腺和性腺雄激素是一组可能至关重要的男性特异性生物因素 鉴于它们驱动男性的性别分化和青春期发育，它们会导致适口性的变化 动物的食物摄入量，它们是神经生物系统内基因转录的有效调节者 与BE相关。此外，动物研究和我们的初步人体数据表明，雄激素水平较低 （例如，睾酮）可预测较高的 BE 表型水平以及对 BE 的更强的遗传影响 男性在青春期有这种现象，但还没有大规模的研究检验这些生物过程。更大规模的研究 涵盖青春期成熟的整个范围（例如，肾上腺初现到性腺初现）并且全面 评估肾上腺和性腺雄激素是下一步必要的步骤，它将增强科学的严谨性和 提供关键的再现性和转化数据。拟议工作的长期目标是 确定雄激素对青春期男孩 BE 表型和遗传风险的作用。具体目标 目的是： 1) 检查肾上腺和/或性腺雄激素水平较低是否会导致男孩的BE 青春期; 2）检查遗传因素是否是驱动肾上腺和肾上腺表型效应的机制 青春期男孩的性腺雄激素对BE的影响。参与者将包括 1,000 名同性男性双胞胎（7 岁至 17) 通过密歇根州立大学双胞胎登记处招募。将进行问卷调查和访谈 对双胞胎和至少一位父母进行测试，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。将收集唾液样本并进行肾上腺和 性腺雄激素水平。多级结构方程模型将用于检查表型效应 青春期期间肾上腺和性腺雄激素对BE的影响。潜在双胞胎调节模型将检查 肾上腺和性腺雄激素水平较低与较强的遗传效应相关的程度 BE在青春期。所有分析还将探讨观察到的效果是否独立于其他因素 （即肥胖、焦虑、抑郁）在青春期发生变化，并与雄激素和 BE 相关。 我们创新的多方法项目的研究结果有可能显着增进对 通过将雄激素确定为导致 BE 的新型神经生物学因素，了解男孩 BE 的原因。 更深入地了解男孩 BE 的病因机制将缩小对假定的神经生物学的搜索范围 系统和基因，有助于改善这些综合征的治疗和预防。