While the BDNF Val66Met polymorphism has been linked to various trauma and anxiety – related psychiatric disorders, limited focus has been on the neural structures that might modulate its relationship with objective measures of threat sensitivity. Therefore, we assessed whether there was an interaction of Val66Met polymorphism with brain area volumes previously associated with anxiety and PTSD, such as the ventromedial prefrontal cortex (vmPFC), insular cortex (IC), and dorsal and ventral anterior cingulate cortices (dACC and vACC), in predicting fear-potentiated psychophysiological response in a clinical sample of Veterans. 110 participants engaged in a fear-potentiated acoustic startle paradigm and provided genetic and imaging data. Fear conditions included no, ambiguous, and high threat conditions (shock). Psychophysiological response measures included electromyogram (EMG), skin conductance response (SCR), and heart rate (HR). PTSD status, trauma history, and demographics were also assessed. There was an interaction of Met allele carrier status with vmPFC, IC, dACC, and vACC volumes for predicting SCR (p < 0.001 for all regions). However, only vmPFC and IC significantly moderated the relationship between Val66Met and psychophysiological response (SCR). The Val66met polymorphism may increase susceptibility to PTSD and anxiety disorders via an interaction with reduced vmPFC and IC volume. Future research should examine whether these relationships might be associated with a differential course of illness longitudinally or response to treatments.

虽然 BDNF Val66Met 多态性与各种创伤和焦虑相关的精神疾病有关，但对可能调节其与威胁敏感性客观测量关系的神经结构的关注有限。因此，我们评估了 Val66Met 多态性是否与先前与焦虑和 PTSD 相关的脑区体积相互作用，例如腹内侧前额叶皮层 (vmPFC)、岛叶皮层 (IC) 以及背侧和腹侧前扣带皮层 (dACC 和 vACC )，预测退伍军人临床样本中恐惧增强的心理生理反应。110 名参与者参与了增强恐惧的听觉惊吓范式，并提供了遗传和成像数据。恐惧条件包括无、模棱两可和高威胁条件（休克）。心理生理反应测量包括肌电图（EMG）、皮肤电导反应（SCR）和心率（HR）。还评估了 PTSD 状态、创伤史和人口统计数据。Met 等位基因携带状态与 vmPFC、IC、dACC 和 vACC 体积之间存在交互作用，可预测 SCR（所有地区的p  < 0.001）。然而，只有 vmPFC 和 IC 显着缓和了 Val66Met 与心理生理反应 (SCR) 之间的关系。Val66met 多态性可能通过与减少的 vmPFC 和 IC 体积的相互作用增加对 PTSD 和焦虑症的易感性。未来的研究应该检查这些关系是否可能与纵向疾病的不同过程或对治疗的反应有关。