Childhood stress, grown-up brain networks: corticolimbic correlates of threat-related early life stress and adult stress response.
Childhood stress, grown-up brain networks: corticolimbic correlates of threat-related early life stress and adult stress response.
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DOI：
10.1017/s0033291717002628
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发表时间：
2018-05
影响因子：
6.9
通讯作者：
Pizzagalli DA
中科院分区：
文献类型：
--
作者：
Kaiser RH;Clegg R;Goer F;Pechtel P;Beltzer M;Vitaliano G;Olson DP;Teicher MH;Pizzagalli DA
暴露于与威胁相关的早期生活压力（ELS）与成年期压力相关疾病的脆弱性有关，通过破坏参与压力反应和调节的皮质边缘回路而引起。然而，以前的研究ELS没有检查皮质边缘回路的内在强度和灵活性，这可能是特别重要的适应性应激反应，或这些方面的皮质边缘功能障碍和急性应激反应在成年期之间的关联。70名未服药的女性在威胁相关的ELS的历史不同完成了功能磁共振成像扫描，以评估体素静态（整体）和动态（一系列滑动窗口的变化）静息状态功能连接（RSFC）的双边杏仁核。在一个单独的会议和子集的参与者（n=42），唾液皮质醇和影响的措施，收集在社会评价的压力挑战。威胁相关ELS的严重程度越高，杏仁核和左背外侧前额叶皮层（DLPFC）之间的静态RSFC越负，杏仁核和喙前扣带皮层（rACC）之间的动态RSFC越高。静态杏仁核-DLPFC拮抗作用介导了更高的严重程度的威胁相关的ELS和钝化的皮质醇对压力的反应之间的关系，但动态杏仁核-rACC连接的增加削弱了这种介导的效果，并与更积极的应激后情绪。与威胁相关的ELS与外侧皮质边缘回路内的RSFC相关，这反过来又与急性应激的钝化生理反应相关。值得注意的是，杏仁核和rACC之间的灵活性增加弥补了这种静态破坏，这表明更动态的内侧皮质边缘回路可能是恢复健康应激反应的关键。
Exposure to threat-related early life stress (ELS) has been related to vulnerability for stress-related disorders in adulthood, putatively via disrupted corticolimbic circuits involved in stress response and regulation. However, previous research on ELS has not examined both the intrinsic strength and flexibility of corticolimbic circuits, which may be particularly important for adaptive stress responding, or associations between these dimensions of corticolimbic dysfunction and acute stress response in adulthood. Seventy unmedicated women varying in history of threat-related ELS completed a functional magnetic resonance imaging scan to evaluate voxelwise static (overall) and dynamic (variability over a series of sliding windows) resting-state functional connectivity (RSFC) of bilateral amygdala. In a separate session and subset of participants (n=42), measures of salivary cortisol and affect were collected during a social-evaluative stress challenge. Higher severity of threat-related ELS was related to more strongly negative static RSFC between amygdala and left dorsolateral prefrontal cortex (DLPFC), and elevated dynamic RSFC between amygdala and rostral anterior cingulate cortex (rACC). Static amygdala-DLPFC antagonism mediated the relationship between higher severity of threat-related ELS and blunted cortisol response to stress, but increased dynamic amygdala-rACC connectivity weakened this mediated effect and was related to more positive post-stress mood. Threat-related ELS was associated with RSFC within lateral corticolimbic circuits, which in turn was related to blunted physiological response to acute stress. Notably, increased flexibility between the amygdala and rACC compensated for this static disruption, suggesting that more dynamic medial corticolimbic circuits might be key to restoring healthy stress response.