A developmentally-sensitive mechanism underlying the escalation of adolescent social anxiety

摘要 社交焦虑症(SAD)是一种慢性损害疾病，通常出现在青春期和 影响了大约10%的人口。SAD的治疗应答率明显低于其他焦虑症 疾病，因此迫切需要确定新的治疗目标，以便为新的干预措施提供信息 治疗这种难以治疗的疾病。我们建议通过测试一种了解发育情况的、 青春期早期到中期社交焦虑症状(SA)恶化的机制模型；我们的 模型的中心是对负面评估的恐惧(FNE)和在同伴面前对错误的高度警惕，以及 对额部大脑振荡的关注是这种升级的核心。青春期是一个敏感的时期 社会认知和认知控制的发展。在心理层面上，社会恐惧和FNE表现出 在青春期，鉴于同伴在这一发展过程中的重要性与日俱增，规范性有所提高 窗户。在神经层面上，作为社会认知和认知控制基础的额叶大脑系统表现出 整个青春期的长期发育，包括额叶皮质和相关的4-8赫兹的发育 “theta”振荡与认知控制有因果关系。我们的中心假设是青少年会增加 在FNE中，伴随着额叶皮质的发育，创造了一个不适应的反馈回路：青少年成为 对社交环境中的错误保持高度警惕，进一步增加FNE，最终损害SA。我们的模型预测 (目标1)FNE的发育增加导致对在存在的情况下的表现的更多的关注 同龄人，这反过来又放大了对错误的高度警惕(即增加了与错误相关的theta的强度 振荡)。我们进一步预测(目标2)，增加对错误的过度警惕会导致更多的批判性自我 评估和确认最初的恐惧，随着时间的推移，这会使FNE/SA恶化。此外，我们预测青少年 在内侧-外侧额叶皮质的theta振荡表现出更大同步性的人风险最大 将显示FNE/SA的最大增幅。为了测试我们的模型，我们将收集一个加速的纵向研究 在256名青少年中，年龄跨度为11-15岁，生物学上为男性/女性，年龄在FNE/SA之间。参与者将 在记录EEG时，在同伴在场/不在场的情况下(通过Zoom)完成修改后的认知控制任务。带着一个 展望未来的翻译工作，我们还将(目标3)建立我们神经测量的生态有效性 通过测试在社交交互任务中指示SA的微编码行为的链接。鉴于这种升级 在青春期和更广泛的社会背景下，我们也将测量、控制和探索 青春期的可能调节作用，以及社会和人口变量的影响。一个关键的优势 我们的团队在发展精神病理学和实验方面都有过硬的记录。 治疗学，为将该项目的发现转化为基于大脑的新疗法提供了一条明确的途径 从而缩短了“从板凳到床边”的距离。

Abstract Social anxiety disorder (SAD) is a chronic, impairing condition that typically emerges during adolescence and affects about 10% of the population. Treatment response rates for SAD are markedly lower than for other anxiety disorders, thus presenting an urgent need to identify novel therapeutic targets that can inform new interventions for this difficult-to-treat disorder. We propose to address this need by testing a developmentally-informed, mechanistic model of the escalation of impairing social anxiety symptoms (SA) in early-to-mid adolescence; our model centers on Fear of Negative Evaluation (FNE) and Hypervigilance for Errors in the presence of peers, with a focus on frontal brain oscillations as central to this escalation. Adolescence represents a sensitive period for the development of social cognition and cognitive control. At the psychological level, social fears and FNE exhibit normative increases across adolescence, given the increasing importance of peers during this developmental window. At the neural level, frontal brain systems underlying social cognition and cognitive control exhibit protracted development across adolescence, including development of the frontal cortex and associated 4-8 Hz “theta” oscillations causally implicated in cognitive control. Our central hypothesis is that adolescent increases in FNE, alongside development of the frontal cortex, create a maladaptive feedback loop: adolescents become Hypervigilant to Errors in social settings, further increasing FNE, and ultimately, impairing SA. Our model predicts (Aim 1) that developmental increases in FNE lead to increased concerns over performance in the presence of peers, which in turn amplifies Hypervigilance for Errors (that is, increased strength of error-related theta oscillations). We further predict (Aim 2) that increased Hypervigilance for Errors leads to more critical self- evaluations and confirmations of initial fears, which worsen FNE/SA over time. Moreover, we predict adolescents who exhibit greater synchrony in theta oscillations across medial-lateral frontal cortex are at greatest risk and will display the largest increases in FNE/SA. To test our model, we will collect an accelerated longitudinal study of 256 adolescents, spanning ages 11-15, biologically male/female, and ranging in FNE/SA. Participants will complete a modified cognitive control task in peer presence/absence (via Zoom) as EEG is recorded. With an eye toward future translational work, we will also (Aim 3) establish the ecological validity of our neural measures by testing links to micro-coded behaviors indicative of SA within a social interaction task. Given that escalation of SA occurs during puberty and within a broader social context, we will also measure, control for, and explore the possible moderating roles of puberty, as well as effects of social and demographic variables. A key strength of this proposal is that our team has a proven record in developmental psychopathology and experimental therapeutics, providing a clear path for translating findings from this project into novel, brain-based therapeutics and thereby shortening the distance “from bench to bedside.”