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

广泛性焦虑症（GAD）是一种以持续性和夸大性为特征的衰弱性疾病， 担心了它可以破坏性地干扰日常功能，并与健康状况不佳有关， 负面的经济和社会后果。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12个月的患病率为3.1%。与儿童和青少年的稳定比率相比， 年轻的青少年，新发GAD从16岁到26岁大幅增加，这表明 从青春期后期到成年早期的过渡是GAD的关键高风险阶段。杏仁前核 电路，特别是杏仁核和前扣带皮层（ACC）之间的功能相互作用， 在威胁处理和情绪调节中起关键作用，并与焦虑有关 紊乱具体来说，ACC中类似成人的连接/活动似乎出现在青春期后期， 作为一种有效的自上而下的抑制性调节逐渐发展到成年期。有可能 杏仁核-ACC相互作用的发育偏差可能触发GAD的发展， 从青春期后期到成年早期的过渡期。因此，一项横断面多模式研究（fMRI+MRS） [功能性MRI +磁共振波谱]）旨在检查 杏仁核-ACC回路在16至26岁之间的健康（N = 40）和焦虑（N = 40）参与者。的 这项研究的首要目标是揭示一个综合的功能神经化学生物标志物， 相对于焦虑的发展。具体来说，功能磁共振成像将用于测量功能之间的连接， 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GABA（γ- 在ACC中的功能连接中断和神经化学不平衡， 在这项研究中，可以作为客观和发展敏感的标记，用于识别风险个体， GAD的早期干预和预防。健康人和老年人的综合功能-神经化学生物标志物 焦虑的发展也可以指导靶向多巴胺能的新治疗的发展， 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.