Brain and behavior in individuals with intersex conditions

双性人的大脑和行为

• 批准号: 9285813
• 负责人: Melissa Hines
• 金额: $ 38万
• 依托单位: UNIVERSITY OF CAMBRIDGE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-14 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9285813
• 关键词: Adrenal Glands; Affect; Age; Alzheimer' s Disease; Amygdaloid structure; Androgens; Animal Experimentation; Area; Basal Ganglia; Behavior; Behavior Disorders; Behavioral; Birth; Brain; Brain Injuries; Brain Mapping; Brain imaging; Brain region; California; Cell Survival; Cerebellum; Cerebrum; Characteristics; Clinical; Clinical Management; Clinical Research; Communities; Complete Androgen-Insensitivity Syndrome; Conduct Disorder; Congenital adrenal hyperplasia; Data; Development; Diffusion Magnetic Resonance Imaging; Disease; Empathy; Endocrine Disruptors; Estradiol; Ethics; Exposure to; Eye; Female; Foundations; Gender; Globus Pallidus; Glucocorticoids; Hereditary Disease; Hippocampus (Brain); Hormones; Human; Human Development; Image; Image Analysis; Imaging Techniques; Imaging technology; Impaired cognition; Individual; Intersex; Intervention; Life; Limbic System; Link; Location; Los Angeles; Magnetic Resonance Imaging; Mammals; Maps; Medical; Mental Depression; Mental disorders; Motor; Multimodal Imaging; Nature; Neonatal; Neurites; Parietal; Parkinson Disease; Participant; Patients; Physical aggression; Play; Population; Pregnancy; Prevention; Psyche structure; Reporting; Research; Research Infrastructure; Resolution; Resources; Rodent; Role; Rotation; Sex Characteristics; Shapes; Structure; Suggestion; Sum; Syndrome; Techniques; Testosterone; Thick; Time; Universities; Woman; Work; androgenic; base; behavior measurement; behavioral outcome; brain behavior; brain shape; critical period; design; environmental agent; experience; imaging approach; improved; indexing; male; men; nervous system disorder; neurochemistry; neuroimaging; neuromechanism; offspring; prenatal; prenatal exposure; prenatal influence; prevent; programs; public health relevance; putamen; sex; sex development disorder; tool

 DESCRIPTION (provided by applicant): Studies of non-human mammals show that androgens, particularly testosterone (T), during early development play a major role in sexual differentiation of the brain, with long-term consequences for behavior. Research on clinical populations suggests that prenatal T exposure has similar effects in humans, increasing male-typical behavior and reducing female-typical behavior. Almost nothing is known, however, about the impact of early T exposure on the structure of the human brain. In addition, the brain mechanisms underlying T-related behavioral changes are unknown. This project will study brain structure and behavior in individuals with one of two disorders of sex development (DSD, also called intersex conditions) that are characterized by androgen abnormality beginning prenatally: 1. Congenital adrenal hyperplasia (CAH), which causes overproduction of adrenal androgens; and 2. Complete androgen insensitivity syndrome (CAIS), which involves an inability to respond to androgens, and so an effective lack of androgen exposure. CAH affects both males and females, and 35 men and 35 women with CAH will be compared to 35 male and 35 female controls. Individuals with CAIS are XY females, and 35 females with CAIS will be compared to 35 male and 35 female controls. State-of- the-art imaging technology will be used to map brain structure. Also, aspects of behavior, known to show substantial sex differences, and for which there is evidence of a relationship to prenatal T exposure, will be assessed. Specifically, these are mental rotation ability, targeting ability, and propensities to physical aggression (where men score higher than women), and verbal fluency, fine motor ability and empathy (where women score higher than men). The information obtained will provide convergent evidence regarding the influence of T on human brain and behavior. Convergent evidence is important because ethical considerations preclude experimental manipulations of T during early human development. Instead, naturally occurring conditions that involve T excess or deficiency will be studied. Each condition involves consequences in addition to T abnormality. Therefore, confidence that testosterone caused any brain or behavior differences is strengthened when data from both conditions suggest this conclusion. For instance, prior research indicates that, with respect to physical aggression, men score higher than women, and females with CAH score higher than other females. If XY females with CAIS resemble women rather than men in regard to physical aggression, confidence that T is the responsible agent will be increased. The information obtained will enhance understanding of the neural mechanisms involved in sexual differentiation of human brain and behavior, and so will be relevant to the many psychological disorders that differ by sex. It will also be relevant to clinical management of individuals who have experienced T abnormality before birth, for any of several reasons, including genetic disorders, such as CAH or CAIS, or other disorders of sex development, maternal treatment with hormones during pregnancy, or contact with environmental endocrine disruptors.

 描述(申请人提供)：对非人类哺乳动物的研究表明，雄激素，特别是睾酮(T)，在早期发育过程中对大脑的性别分化起主要作用，并对行为产生长期影响。对临床人群的研究表明，产前暴露T对人类也有类似的影响，增加男性典型行为，减少女性典型行为。然而，关于早期T暴露对人脑结构的影响，人们几乎一无所知。此外，T相关行为变化背后的大脑机制尚不清楚。这个项目将研究患有两种性发育障碍(DSD，也称为中间性条件)之一的人的大脑结构和行为，这两种疾病的特征是从产前开始雄激素异常：1.先天性肾上腺增生(CAH)，导致肾上腺雄激素过量产生；2.完全雄激素不敏感综合征(CAIS)，涉及对雄激素的反应能力，因此有效地缺乏雄激素暴露。CAH对男性和女性都有影响，患有CAH的35名男性和35名女性将与35名男性和35名女性对照。患有CAI的个体是XY女性，而患有CAI的35名女性将与35名男性和35名女性对照。最先进的成像技术将被用于绘制大脑结构图。此外，已知的表现出显著性别差异的行为方面，以及有证据表明与产前T暴露有关的方面，将被评估。具体地说，这些是心理旋转能力、目标能力和身体攻击倾向(男性得分高于女性)，以及语言流畅性、精细运动能力和同理心(女性得分高于男性)。所获得的信息将为T对人类大脑和行为的影响提供一致的证据。一致的证据很重要，因为伦理考虑排除了在人类早期发育过程中对T进行实验操作的可能性。取而代之的是，涉及T过多或缺乏的自然发生的条件将被研究。除T异常外，每种情况都涉及后果。因此，当两种情况的数据都表明这一结论时，睾丸激素导致大脑或行为差异的信心就会增强。例如，先前的研究表明，在身体攻击方面，男性得分高于女性，女性CAH得分高于其他女性。如果患有CAI的XY女性在身体攻击方面更像女性而不是男性，那么T是负责任的因素的信心将会增强。所获得的信息将加强对涉及人类大脑和行为的性别分化的神经机制的理解，因此将与许多因性别而异的心理障碍有关。它还将与出生前经历过T异常的个人的临床管理相关，这些原因包括遗传疾病，如CAH或CAI，或其他性发育障碍，怀孕期间使用激素的产妇治疗，或接触环境内分泌干扰物。