Yale Child Study Center, Yale School of Medicine, Yale University, 230 S. Frontage Road, New Haven, CT 06519, USA.
Emotion and Development Branch, National Institute of Mental Health, Bethesda, MD 20854, USA.
J Affect Disord. 2021 Dec 1;295:920-929. doi: 10.1016/j.jad.2021.08.117. Epub 2021 Sep 4.
Anxiety and irritability frequently co-occur in youth and are mediated by aberrant threat responses. However, empirical evidence on neural mechanisms underlying this co-occurrence is limited. To address this, we apply data-driven latent phenotyping to data from a prior report of a well-validated threat extinction recall fMRI paradigm.
Participants included 59 youth (28 anxiety disorder, 31 healthy volunteers; Mage=13.15 yrs) drawn from a transdiagnostic sample of 331 youth, in which bifactor analysis was conducted to derive latent factors representing shared vs. unique variance of dimensionally-assessed anxiety and irritability. Participants underwent threat conditioning and extinction. Approximately three weeks later, during extinction recall fMRI, participants made threat-safety discriminations under two task conditions: current threat appraisal and explicit recall of threat contingencies. Linear mixed-effects analyses examined associations of a "negative affectivity" factor reflecting shared anxiety and irritability variance with whole-brain activation and task-dependent amygdala connectivity.
During recall of threat-safety contingencies, higher negative affectivity was associated with greater prefrontal (ventrolateral/ventromedial, dorsolateral, orbitofrontal), motor, temporal, parietal, and occipital activation. During threat appraisal, higher negative affectivity was associated with greater amygdala-inferior parietal lobule connectivity to threat/safety ambiguity.
Sample included only healthy youth and youth with anxiety disorders. Results may not generalize to other diagnoses for which anxiety and irritability are also common, and our negative affectivity factor should be interpreted as anxiety disorders with elevated irritability. Reliability of some subfactors was poor.
Aberrant amygdala-prefrontal-parietal circuitry during extinction recall of threat-safety stimuli may be a mechanism underlying the co-occurrence of pediatric anxiety and irritability.
焦虑和易怒在年轻人中经常同时出现，这是由异常的威胁反应介导的。然而，关于这种同时发生的神经机制的实证证据有限。为了解决这个问题，我们应用数据驱动的潜在表型分析方法，对先前一项经过充分验证的威胁消退回忆 fMRI 范式的报告数据进行分析。
参与者包括 59 名年轻人（28 名焦虑障碍患者，31 名健康志愿者；平均年龄=13.15 岁），他们来自一个 331 名年轻人的跨诊断样本，其中进行了双因素分析，以得出代表焦虑和易怒维度评估的共同和独特方差的潜在因素。参与者接受了威胁条件作用和消退。大约三周后，在消退回忆 fMRI 期间，参与者在两种任务条件下进行威胁-安全辨别：当前威胁评估和威胁条件的明确回忆。线性混合效应分析检查了反映共同焦虑和易怒方差的“负性情感”因素与全脑激活和任务相关杏仁核连接的关联。
在回忆威胁-安全条件时，较高的负性情感与前额叶（腹外侧/腹内侧、背外侧、眶额）、运动、颞叶、顶叶和枕叶的激活增加有关。在威胁评估时，较高的负性情感与杏仁核-下顶叶小叶到威胁/安全模糊性的连接增加有关。
样本仅包括健康的年轻人和患有焦虑障碍的年轻人。结果可能不适用于焦虑和易怒也很常见的其他诊断，我们的负性情感因素应被解释为焦虑障碍伴有升高的易怒。一些子因素的可靠性较差。
在威胁-安全刺激的消退回忆期间，杏仁核-前额叶-顶叶回路的异常可能是儿童焦虑和易怒同时发生的机制。
