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.

摘要