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（应用程序提供）：非人类哺乳动物的研究表明，早期发育期间雄激素（尤其是睾丸激素（T））在大脑的性分化中起着重要作用，对行为产生了长期后果。对临床人群的研究表明，产前T暴露对人类具有相似的影响，增加了男性典型行为并减少了女性典型行为。然而，几乎一无所知，关于早期暴露对人脑结构的影响。另外，与T相关行为变化的基础机制尚不清楚。该项目将研究患有两种性发育障碍之一（DSD，也称为双性恋疾病）的个体中的大脑结构和行为，其特征是从产前开始：1。先天性肾上腺增生增生（CAH），导致过度生产肾上腺雄激素； 2。完全雄激素不敏感综合征（CAI），涉及无法对雄激素反应，因此有效缺乏雄激素暴露。 CAH会影响男性和女性，将35名男性和35名患有CAH的女性与35名男性和35名女性对照组进行比较。患有CAI的个体是XY女性，将35名患有CAI的女性与35名男性和35名女性对照组进行比较。最先进的成像技术将用于绘制大脑结构。同样，将评估行为的各个方面，即表现出很大的性别差异，并且有证据表明与产前T暴露有关系。具体而言，这些是精神旋转能力，靶向能力以及对身体侵略的政策（男性得分高于女性）以及口头流利，良好的运动能力和同理心（女性得分高于男性）。获得的信息将提供有关T对人脑和行为影响的收敛证据。收敛证据很重要，因为道德考虑排除了早期人类发展过程中T的实验操作。取而代之的是，将研究涉及T超过或缺乏的天然发生条件。除T异常外，每种情况都涉及后果。因此，当来自两种情况的数据表明这一结论时，对睾丸激素引起任何大脑或行为差异的信心将得到加强。例如，先前的研究表明，关于身体侵略，男性得分高于女性，而CAH的女性得分高于其他女性。如果Xy女性与CAIS相似，在身体侵略方面类似于女性，而不是男性，则对T是负责人的信心将增加。获得的信息将增强对人脑和行为性别分化的神经机制的理解，因此将与性别不同的许多心理疾病有关。这也将与出生前在出生前经历过异常的个体的临床管理有关，这是出于多种原因，包括遗传疾病，例如CAH或CAIS，或其他性发育的其他疾病，在怀孕期间使用马匹治疗或与环境内分泌干扰物接触。