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Brain and behavior in individuals with intersex conditions

双性人的大脑和行为

基本信息

批准号：
9540059
负责人：
Melissa Hines
金额：
$ 38.07万
依托单位：
UNIVERSITY OF CAMBRIDGE
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-08-14 至 2021-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9540059
关键词：
Adrenal Glands Adrenal hyperplasia 2 Affect Age Alzheimer&apos 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 Genetic Diseases Globus Pallidus Glucocorticoids 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 rare condition sex sex development disorder tool

项目摘要

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T暴露对人类有类似的影响，增加男性典型行为，减少女性典型行为。然而，关于早期接触T对人脑结构的影响，几乎一无所知。此外，T相关行为变化的大脑机制尚不清楚。该项目将研究两种性别发育障碍（DSD，也称为中间性条件）之一的个体的大脑结构和行为，其特征是产前开始的雄激素异常：1。先天性肾上腺增生症（CAH），导致肾上腺雄激素过度分泌;和2。完全雄激素不敏感综合征（CAIS），涉及对雄激素无反应，因此有效缺乏雄激素暴露。CAH影响男性和女性，35名男性和35名女性CAH患者将与35名男性和35名女性对照组进行比较。患有CAIS的个体为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。此外，行为方面，已知显示出实质性的性别差异，并有证据表明，产前T暴露的关系，将进行评估。具体来说，这些是心理旋转能力，目标定位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会聚证据。收敛的证据是很重要的，因为伦理方面的考虑排除了在人类早期发育过程中对T的实验操作。相反，将研究涉及T过量或缺乏的自然发生的条件。每种情况都涉及T细胞异常以外的后果。因此，当这两种情况的数据都表明这一结论时，睾丸激素导致任何大脑或行为差异的信心得到了加强。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XY女性与CAIS类似的女性，而不是男性的身体侵略方面，T是负责任的代理人的信心将增加。所获得的信息将加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障碍有关。它还将与出生前经历T异常的个体的临床管理有关，这些异常是由于几种原因中的任何一种，包括遗传性疾病，如CAH或CAIS，或其他性发育障碍，怀孕期间用激素进行的母体治疗，或与环境内分泌干扰物接触。