The Influence of Fetal Testosterone on Emotional Processing, Amydala Neurocircuitry, and Risk for Affective Disorders in Childhood

胎儿睾酮对情绪处理、杏仁核神经回路和儿童时期情感障碍风险的影响

• 批准号: 9330938
• 负责人: Megan Marie Herting
• 金额: $ 18.14万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-12 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9330938
• 关键词: Address; Adolescence; Adolescent; Adolescent Psychiatry; Affect; Affective; Age; Age of Onset; Amygdaloid structure; Animals; Anisotropy; Anxiety; Area; Arousal; Behavioral; Biological; Brain; Child; Child Psychiatry; Childhood; Clinical; Congenital adrenal hyperplasia; Data; Development; Diffusion Magnetic Resonance Imaging; Early Intervention; Early identification; Electrocardiogram; Emotional; Emotions; Endocrinology; Etiology; Exhibits; Exposure to; Eye; Face; Family; Female; Foundations; Functional Magnetic Resonance Imaging; Funding; Galvanic Skin Response; Goals; Gonadal Steroid Hormones; Heart Rate; Hormonal; Hormonal Change; Hormones; Human; Image; Impairment; Individual; Individual Differences; International; K-Series Research Career Programs; Laboratories; Lead; Link; Magnetic Resonance Imaging; Medical; Mental Depression; Mental Health; Mental disorders; Mentors; Mentorship; Mind; Modality; Mood Disorders; Morphology; Normal Range; Pathway interactions; Patient Self-Report; Patients; Pattern; Phase; Phenotype; Physiological; Physiology; Prefrontal Cortex; Prevalence; Prevention program; Psychopathology; Psychophysiology; Puberty; Quality of life; Reaction Time; Reading; Recruitment Activity; Reporting; Research; Research Personnel; Rest; Risk; Role; Sampling; Sex Characteristics; Stimulus; Structure; Surface; System; Techniques; Testing; Testosterone; Training; Youth; affective neuroscience; attentional bias; base; behavioral response; boys; brain behavior; career; early onset; emotional behavior; emotional stimulus; experience; fetal; girls; imaging modality; improved; in utero; multidisciplinary; multimodality; neurodevelopment; neuroimaging; phase change; prenatal; relating to nervous system; response; sex; trend; white matter

Abstract Understanding neurodevelopmental and early onset origins of mental disorders is essential to improve the quality of life for children and adolescents and their families, and to reduce societal burden through early identification and intervention. My long-term career goal is to become a fully funded, independent investigator to study the role of biological sex and hormones in emotional neurodevelopment and risk for childhood and adolescent onset of affective disorders. Fetal hormones may have permanent organizational effects that lay the foundation for, and may even limit, subsequent organizational and activational effects of sex hormones on brain circuits during puberty. Thus, the interaction of both fetal and pubertal hormone exposure may contribute to individual and sex-based differences in risk for affective disorders. Although I have extensive research experience studying typical neurodevelopment using magnetic resonance imaging (MRI) methods, the present application will provide me with multidisciplinary training and mentorship in assessing emotional processing and mental health in children and adolescents, as well as recruiting and collecting imaging data in pediatric clinical samples. The specific research aims of this proposal allow for development of these skillsets by investigating how increased fetal testosterone levels impact emotional processing and its neural substrates, including the amygdala and its connectivity with the prefrontal cortex, in children. To accomplish this goal, I will address these pressing questions by studying patients with a clinical condition that leads to high fetal testosterone exposure, known as classical Congenital Adrenal Hyperplasia (CAH). Utilizing emotional behavioral tasks both inside and outside the scanner, recording tonic and phasic heart rate and skin conductance activity, and implementing multi-modal magnetic resonance imaging (MRI), I will investigate emotional processing, as well as amygdala and prefrontal structure and connectivity in 40 CAH children (ages 8 to 12 years, 50% girls) and 40 controls matched for age, sex, and early pubertal maturity. By determining how fetal testosterone influences emotional neurodevelopment in late childhood in the current study, future research will focus on longitudinally following these youth to investigate how hormonal changes during mid-to- late puberty may interact with fetal hormonal programming to confer risk for affective disorders. Long-term goals of the proposal are to enhance and refine my training in child and adolescent psychiatry, affective neuroscience, pediatric clinical neuroimaging, and endocrinology. Ultimately, the opportunity of a mentored career development award will be a critical next step to building a productive developmental neuroimaging laboratory dedicated to improving our understanding of, and creating better prevention programs for, individual and sex differences in the risk for affective disorders that begin to emerge during childhood and adolescence.

抽象的 了解精神障碍的神经发育和早期发病起源对于改善精神障碍至关重要 儿童和青少年及其家庭的生活质量，并通过早期教育减轻社会负担 识别和干预。我的长期职业目标是成为一名资金充足的独立调查员 研究生物性别和激素在情绪神经发育以及儿童和青少年风险中的作用 青少年时期出现情感障碍。胎儿激素可能具有永久性的组织影响 性激素随后的组织和激活作用的基础，甚至可能限制 青春期的大脑回路。因此，胎儿和青春期激素暴露的相互作用可能有助于 情感障碍风险的个体和性别差异。虽然我有广泛的研究 使用磁共振成像（MRI）方法研究典型神经发育的经验，目前 应用程序将为我提供评估情绪处理方面的多学科培训和指导 儿童和青少年的心理健康，以及招募和收集儿科的影像数据 临床样本。该提案的具体研究目标允许通过以下方式发展这些技能 研究胎儿睾酮水平的增加如何影响情绪处理及其神经基质， 包括儿童的杏仁核及其与前额皮质的连接。为了实现这个目标，我将 通过研究患有导致高胎儿风险的临床状况的患者来解决这些紧迫的问题 睾酮暴露，称为经典先天性肾上腺增生症（CAH）。利用情感 扫描仪内部和外部的行为任务，记录强直和阶段性心率和皮肤 电导活动，并实施多模态磁共振成像（MRI），我将研究 40 名 CAH 儿童（年龄 8 至 12 岁，50% 女孩）和 40 名年龄、性别和青春期提前成熟相匹配的对照。通过确定 在当前的研究中，未来胎儿睾酮如何影响儿童晚期的情绪神经发育 研究将集中于纵向跟踪这些年轻人，以调查中年至成年期间荷尔蒙的变化。 青春期后期可能与胎儿荷尔蒙编程相互作用，从而增加患情感障碍的风险。长期 该提案的目标是加强和完善我在儿童和青少年精神病学、情感学方面的培训 神经科学、儿科临床神经影像学和内分泌学。最终获得导师指导的机会 职业发展奖将是建立富有成效的发展神经影像学的关键下一步 实验室致力于提高我们对个人的了解并为其制定更好的预防计划 童年和青春期开始出现的情感障碍风险存在性别差异。