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（由申请人提供）：对非人类哺乳动物的研究表明，雄激素，特别是睾酮（T），在早期发育过程中在大脑的性别分化中发挥着重要作用，对行为产生长期影响。对临床人群的研究表明，产前接触 T 对人类也有类似的影响，增加男性典型行为并减少女性典型行为。然而，关于早期 T 暴露对人脑结构的影响几乎一无所知。此外，与 T 相关的行为变化背后的大脑机制尚不清楚。该项目将研究患有两种性发育障碍（DSD，也称为双性病症）之一的个体的大脑结构和行为，其特征是从产前开始出现雄激素异常： 1. 先天性肾上腺增生（CAH），导致肾上腺雄激素产生过多； 2. 完全雄激素不敏感综合征（CAIS），其涉及无法对雄激素做出反应，因此实际上缺乏雄激素暴露。 CAH 同时影响男性和女性，将 35 名患有 CAH 的男性和 35 名女性与 35 名男性和 35 名女性对照者进行比较。患有 CAIS 的个体是 XY 女性，将 35 名患有 CAIS 的女性与 35 名男性和 35 名女性对照进行比较。最先进的成像技术将用于绘制大脑结构图。此外，还将对已知表现出显着性别差异且有证据表明与产前 T 暴露相关的行为方面进行评估。具体来说，这些是心理旋转能力、瞄准能力和身体攻击倾向（男性得分高于女性），以及言语流畅性、精细运动能力和同理心（女性得分高于男性）。获得的信息将为T对人类大脑和行为的影响提供聚合证据。趋同的证据很重要，因为伦理考虑排除了人类早期发育过程中对 T 的实验操作。相反，我们将研究涉及 T 过量或缺乏的自然发生条件。除了 T 异常之外，每种情况还涉及后果。因此，当两种情况的数据表明这一结论时，睾丸激素导致任何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，患有 CAH 的女性得分高于其他女性。如果患有 CAIS 的 XY 女性在身体攻击方面类似于女性而不是男性，那么就会增加 T 是责任主体的信心。获得的信息将增强对人类大脑和行为性别分化所涉及的神经机制的理解，因此将与许多因性别而异的心理疾病相关。它还与出生前经历 T 异常的个体的临床管理相关，这些异常的原因有多种，包括遗传性疾病，如 CAH 或 CAIS，或其他性发育障碍、母亲在怀孕期间接受激素治疗或接触环境内分泌干扰物。