Testing Dual Mechanism Model of Adolescent Anxiety and Related Sex Differences

测试青少年焦虑和相关性别差异的双重机制模型

• 批准号: 10247844
• 负责人: Jeffrey Martin SPIELBERG
• 金额: $ 21.35万
• 依托单位: DELAWARE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10247844
• 关键词: Adolescence; Adolescent; Adolescent Development; Adult; Anxiety; Axon; Brain; Communication; Data; Delaware; Development; Effectiveness; Female; Individual; Measures; Mediating; Mental disorders; Methods; Modeling; Myelin; Neurosciences Research; Pathologic; Pathological anxiety; Predisposing Factor; Public Health; Risk; Risk Factors; Sex Differences; Sum; Testing; Testosterone; Work; disability; early adolescence; emotion regulation; girls; high risk; multimodality; myelination; neuroimaging; novel; prepuberty; sex; support network; white matter

Anxiety remains one of the most common forms of mental illness and the 6th leading cause of disability. Anxiety tends to emerge during early adolescence, and this occurs differentially between sexes: rates are equal pre-puberty and become 2-fold greater in females. Thus, identifying factors that predispose towards anxiety is crucial for identifying as-risk individuals early. We have proposed that the development of anxiety in adolescence is due, in part, to differences in the maturation of brain networks supporting emotion regulation. However, mechanisms that influence the development of these networks, and their implications for anxiety, are not well understood. We will test a model incorporating two risk factors (pubertal testosterone and axonal myelination) by collecting neuroimaging data from individuals transitioning into adolescence, half of whom are at high risk for developing anxiety . Aim 1: Work from our lab and others in healthy adolescents/ adults indicates that testosterone dampens the effectiveness of key emotion-regulation circuitry, and this dampening predicted anxiety increases. However, it is unclear if this impacts pathological levels of anxiety. Additionally, white matter integrity in this circuitry is weaker in anxiety, likely disrupting the efficiency of communication. Unfortunately, the mechanism by which this occurs remain unknown; we have proposed that weaker integrity impacts anxiety by exacerbating the impact of testosterone. Importantly, a key driver of white matter integrity is myelination, and these circuits begin myelinating during adolescence. Therefore, Aim 1 uses a novel multi-modal myelin measure to test whether testosterone and myelination impact anxiety, as mediated by changes in emotion-regulation circuitry. Aim 2: The mechanisms that confer greater risk for anxiety in females remain unknown. Our work suggests that females have a higher sensitivity to testosterone in key emotion-regulation circuitry. Thus, Aim 2 tests whether testosterone has a greater impact on emotionregulation circuitry/pathological anxiety in girls. In sum, this project aims to identify mechanisms responsible for the development of adolescent anxiety. This work has the potential for tremendous public health impact by harnessing cutting-edge methods to uncover and validate novel risk trajectories for anxiety.

焦虑仍然是最常见的精神疾病之一，也是导致残疾的第六大原因。 焦虑倾向于在青春期早期出现，这在性别之间存在差异： 在青春期前，女性的体重是男性的两倍。因此，确定易患 焦虑对于早期识别风险个体至关重要。我们提出焦虑的发展 在青春期，部分原因是支持情绪的大脑网络成熟度的差异。 调控然而，影响这些网络发展的机制及其影响 对于焦虑症，还没有很好的理解。我们将测试一个包含两个风险因素（青春期睾酮）的模型 和轴突髓鞘形成）通过收集从个体过渡到青春期的神经影像学数据， 他们中的大多数人都有患焦虑症的高风险。目标1：我们实验室和其他人在健康青少年中的工作/ 成年人的研究表明，睾丸激素会抑制关键的情绪调节回路的有效性， 抑制预期的焦虑增加。然而，目前还不清楚这是否会影响病理水平的焦虑。 此外，该回路中的白色物质完整性在焦虑中较弱，可能会破坏大脑的效率。 通信不幸的是，发生这种情况的机制仍然未知;我们提出， 较弱的完整性通过加剧睾丸激素的影响而影响焦虑。重要的是， 白色物质的完整性是髓鞘形成，这些回路在青春期开始髓鞘形成。因此，Aim 1使用一种新的多模态髓鞘测量来测试睾酮和髓鞘形成是否影响焦虑， 通过情绪调节回路的变化来调节。目标2：增加风险的机制 女性的焦虑仍然未知。我们的研究表明女性对睾丸激素的敏感性更高 关键的情绪调节回路因此，目标2测试了睾丸激素是否对情绪调节有更大的影响 女孩的电路/病理性焦虑。总而言之，该项目旨在确定负责 青少年焦虑症的发展。这项工作有可能对公共卫生产生巨大的影响 通过利用尖端的方法来发现和验证焦虑的新风险轨迹。