Testing Dual Mechanism Model of Adolescent Anxiety and Related Sex Differences

焦虑仍然是最常见的精神疾病形式之一，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，这种情况在性别上有差异： 相同的青春期前，变得比女性大2倍。因此，确定倾向于 焦虑对于及早识别为高危个体至关重要。我们已经提出，焦虑的发展 在青春期，部分原因是支持情绪的大脑网络的成熟程度不同 监管。然而，影响这些网络发展的机制及其影响 对于焦虑症，人们还没有很好的理解。我们将测试一个包含两个风险因素(青春期睾丸激素)的模型 和轴突髓鞘形成)，通过收集过渡到青春期的人的神经成像数据，一半 其中一些人患焦虑症的风险很高。目标1：我们的实验室和其他机构在健康青少年中的工作/ 成年人表示，睾丸激素会抑制关键情绪调节回路的有效性，而这一点 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性的焦虑水平。 此外，在焦虑时，这个回路中的白质完整性较弱，可能会扰乱 沟通。不幸的是，发生这种情况的机制仍不清楚；我们已经提出 较弱的正直会加剧睾丸激素的影响，从而影响焦虑。重要的是，一个关键的驱动力 白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，目标是 1使用一种新的多模式髓鞘测量来测试睾丸激素和髓鞘形成是否影响焦虑，如 通过情绪调节回路的变化来调节。目标2：赋予更大风险的机制 女性的焦虑症仍不清楚。我们的研究表明女性对睾丸激素有更高的敏感度 在关键的情绪调节回路中。因此，Aim 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的机制 对于青少年焦虑症的发展。这项工作有可能对公众健康产生巨大影响 通过利用尖端方法来发现和验证焦虑的新风险轨迹。

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.