Functional and Neurochemical Substrates of Amygdala-Frontal Circuitry across Development and Anxiety

广泛性焦虑症(GAD)是一种以持续和夸张为特征的令人衰弱的疾病 令人担忧。它可以干扰日常功能，并与健康状况不佳有关，以及 负面的金融和社会后果。作为最常见的焦虑症之一，广泛性焦虑症影响着数百万人 美国人每年的12个月患病率为3.1%。与儿童和儿童的稳定发病率相比 更年轻的青少年，新发的广泛性AD从16岁到26岁大幅增加，这表明 从青春期晚期过渡到成年期早期是广泛性AD的关键高危阶段。杏仁核-额叶 回路，特别是杏仁核和前扣带回(ACC)之间的功能相互作用，发挥着 在威胁处理和情绪调节中起关键作用，并与焦虑密切相关 精神错乱。具体地说，ACC中的成人型连接/活动似乎出现在青春期晚期，并且 作为一种有效的自上而下的抑制性调节，逐渐发展到成年。有可能是 杏仁核-ACC相互作用的发育偏差可能触发GAD的发展 从青春期晚期过渡到成年期早期。因此，横断面多模式研究(fMRI+MRS) [功能磁共振+磁共振光谱学])旨在研究 16至26岁的健康(N=40)和焦虑(N=40)参与者的杏仁核-ACC环路。这个 这项研究的首要目标是揭示一种整合的功能-神经化学生物标记物 与焦虑的发展相比。具体地说，功能磁共振成像将用于测量 杏仁核和ACC对社会威胁的反应；1H-MRS将用于测量浓度 主要兴奋性神经递质谷氨酸和主要抑制性神经递质γ-氨基丁酸(γ- 氨基丁酸)。已确定的功能连接障碍和神经化学失衡 这项研究可以作为识别高危个体的客观和发展敏感的标志 早期干预和预防广泛性AD。健康人群和健康人群的功能-神经化学综合生物标记物 焦虑的发展也可以指导针对谷氨酸能和 从神经发育的角度看GABA能系统。

Generalized anxiety disorder (GAD) is a debilitating illness characterized by persistent and exaggerated worrying. It can disruptively interfere with everyday functioning, and is associated with poor health, and negative financial and social outcomes. As one of the most common anxiety disorders, GAD affects millions of Americans each year with a 12-month prevalence of 3.1%. Compared to the stable rates in children and younger adolescents, new onset of GAD increases substantially from 16 to 26 years of age, suggesting the transition from late adolescence to early adulthood as a key high-risk stage for GAD. Amygdala-frontal circuitry, particularly functional interactions between the amygdala and anterior cingulate cortex (ACC), plays a critical role in threat processing and emotional regulation, and has been centrally implicated in anxiety disorders. Specifically, adult-like connectivity/activity in the ACC appears to emerge in late adolescence, and gradually develops into adulthood as an effective top-down inhibitory regulation. It is possible that developmental deviations of the amygdala-ACC interaction may trigger the development of GAD during the transition from late adolescence to early adulthood. Therefore, a cross-sectional multimodal study (fMRI+MRS [functional MRI + magnetic resonance spectroscopy]) is designed to examine the developmental trajectories of amygdala-ACC circuitry in healthy (N = 40) and anxious (N = 40) participants between 16 to 26 years old. The overarching objective of this study is to uncover an integrated functional-neurochemical biomarker for healthy versus anxious development. Specifically, fMRI will be used to measure the functional connectivity between the amygdala and the ACC in response to social threats; 1H-MRS will be used to measure the concentrations of the primary excitatory neurotransmitter glutamate and the primary inhibitory neurotransmitter GABA (γ- aminobutyric acid) in the ACC. Disrupted functional connectivity and imbalanced neurochemistry as identified in this study can serve as objective and developmentally sensitive markers for identifying at-risk individuals for early intervention and prevention of GAD. The integrated functional-neurochemical biomarker of healthy and anxious development can also guide the development of novel treatments targeting at the glutamatergic and GABAergic systems from a neurodevelopmental perspective.