BACKGROUND While translational theories link neurodevelopmental changes in threat learning to pathological anxiety, findings from studies in patients inconsistently support these theories. This inconsistency may reflect difficulties in studying large patient samples with wide age ranges using consistent methods. A dearth of imaging data in patients further limits translational advances. We address these gaps through a psychophysiology and structural brain imaging study in a large sample of patients across the lifespan. METHODS A total of 351 participants (8-50 years of age; 209 female subjects; 195 healthy participants and 156 medication-free, treatment-seeking patients with anxiety) completed a differential threat conditioning and extinction paradigm that has been validated in pediatric and adult populations. Skin conductance response indexed psychophysiological response to conditioned (CS+, CS-) and unconditioned threat stimuli. Structural magnetic resonance imaging data were available for 250 participants. Analyses tested anxiety and age associations with psychophysiological response in addition to associations between psychophysiology and brain structure. RESULTS Regardless of age, patients and healthy comparison subjects demonstrated comparable differential threat conditioning and extinction. The magnitude of skin conductance response to both conditioned stimulus types differentiated patients from comparison subjects and covaried with dorsal prefrontal cortical thickness; structure-response associations were moderated by anxiety and age in several regions. Unconditioned responding was unrelated to anxiety and brain structure. CONCLUSIONS Rather than impaired threat learning, pathological anxiety involves heightened skin conductance response to potential but not immediately present threats; this anxiety-related potentiation of anticipatory responding also relates to variation in brain structure. These findings inform theoretical considerations by highlighting anticipatory response to potential threat in anxiety.

中文翻译：

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预期威胁响应：与焦虑、发育和大脑结构的关联

背景虽然转化理论将威胁学习中的神经发育变化与病理性焦虑联系起来，但对患者的研究结果不一致地支持这些理论。这种不一致可能反映了使用一致方法研究具有广泛年龄范围的大型患者样本的困难。患者影像数据的缺乏进一步限制了转化的进展。我们通过在整个生命周期的大量患者样本中进行心理生理学和结构脑成像研究来解决这些差距。方法 共有 351 名参与者（8-50 岁；209 名女性受试者；195 名健康参与者和 156 名无药物、寻求治疗的焦虑患者）完成了差异威胁条件反射和灭绝范式，该范式已在儿童和成人中得到验证。人口。皮肤电导反应指数化对条件（CS+、CS-）和无条件威胁刺激的心理生理反应。250 名参与者可获得结构磁共振成像数据。除了心理生理学和大脑结构之间的关联之外，分析还测试了焦虑和年龄与心理生理反应的关联。结果 无论年龄大小，患者和健康对照受试者表现出可比的差异威胁条件反射和灭绝。对两种条件刺激类型的皮肤电导反应的大小将患者与比较对象区分开来，并与背侧前额叶皮质厚度共变；在几个地区，结构-反应关联受到焦虑和年龄的影响。无条件反应与焦虑和大脑结构无关。结论 病理性焦虑不是威胁学习受损，而是涉及对潜在但不是立即存在的威胁的皮肤电导反应增强；这种焦虑相关的预期反应增强也与大脑结构的变化有关。这些发现通过强调对焦虑中潜在威胁的预期反应来为理论考虑提供信息。