In the DSM-5, separation anxiety disorder (SAD) is newly classified in the chapter on anxiety, renewing research efforts into its etiology. In this narrative review, we summarize the current literature on the genetic, endocrine, physiological, neural and neuropsychological underpinnings of SAD per se, SAD in the context of panic disorder, separation anxiety symptoms, and related intermediate phenotypes. SAD aggregates in families and has a heritability of ~43%. Variants in the oxytocin receptor, serotonin transporter, opioid receptor µ1, dopamine D4 receptor and translocator protein genes have all been associated with SAD. Dysregulation of the hypothalamus-pituitary-adrenal axis, dysfunctional cortico-limbic interaction and biased cognitive processing seem to constitute further neurobiological markers of separation anxiety. Hypersensitivity to carbon dioxide appears to be an endophenotype shared by SAD, panic disorder and anxiety sensitivity. The identification of biological risk markers and its multi-level integration hold great promise regarding the prediction of SAD risk, maintenance and course, and in the future may allow for the selection of indicated preventive and innovative, personalized therapeutic interventions.

中文翻译：

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分离焦虑和相关表型的神经生物学框架

在 DSM-5 中，分离焦虑症 (SAD) 在焦虑一章中被新分类，重新对其病因进行研究。在这篇叙述性评论中，我们总结了当前关于 SAD 本身的遗传、内分泌、生理、神经和神经心理学基础、恐慌症背景下的 SAD、分离焦虑症状和相关中间表型的文献。SAD 在家庭中聚集，遗传力约为 43%。催产素受体、血清素转运蛋白、阿片受体 μ1、多巴胺 D4 受体和易位蛋白基因的变异都与 SAD 相关。下丘脑-垂体-肾上腺轴的失调、皮质-边缘相互作用功能失调和认知处理偏差似乎构成了分离焦虑的进一步神经生物学标志。对二氧化碳的超敏反应似乎是 SAD、恐慌症和焦虑敏感性共有的一种内表型。生物风险标志物的识别及其多层次整合在预测 SAD 风险、维持和病程方面具有很大的前景，并且在未来可能允许选择指示性的预防性和创新性、个性化的治疗干预措施。