Fan Yan, Herrera-Melendez Ana Lucia, Pestke Karin, Feeser Melanie, Aust Sabine, Otte Christian, Pruessner Jens C, Böker Heinz, Bajbouj Malek, Grimm Simone
Cluster of Excellence "Languages of Emotion",, Freie Universität Berlin, Berlin, Germany; Department of Psychiatry, Campus Benjamin Franklin, Charité Berlin, Berlin, Germany; Dahlem Institute for Neuroimaging of Emotion, Freie Universität Berlin, Berlin, Germany.
Hum Brain Mapp. 2014 Oct;35(10):5328-39. doi: 10.1002/hbm.22553. Epub 2014 May 26.
Recent evidence suggests that early life stress (ELS) changes stress reactivity via reduced resting state functional connectivity (rs-FC) between amygdala and the prefrontal cortex. Oxytocin (OXT) modulates amygdala connectivity and attenuates responses to psychosocial stress, but its effect appears to be moderated by ELS. Here we first investigate the effect of ELS on amygdala-prefrontal rs-FC, and examine whether ELS-associated changes of rs-FC in this neural circuit predict its response to psychosocial stress. Secondly, we explore the joint effect of OXT and ELS on the amygdala-prefrontal circuit. Eighteen healthy young males participated in a resting-state fMRI study of OXT effects using a double-blind, randomized, placebo-controlled, within-subject crossover design. We measured the rs-FC to bilateral amygdalae and subsequently assessed changes of state anxiety and prefrontal responses to psychosocial stress. Multiple linear regressions showed that ELS, specifically emotional abuse, predicted reduced rs-FC between the right amygdala and pregenual anterior cingulate cortex (pgACC), which in turn predicted elevated state anxiety after psychosocial stress. In subjects with lower ELS scores, stronger pgACC-amygdala rs-FC predicted stronger pgACC deactivation during the psychosocial stress task, and this rest-task interaction was attenuated by OXT. In subjects with higher ELS scores however, the rest-task interaction was altered and OXT showed no significant effect. These findings highlight that ELS reduces pgACC-amygdala rs-FC and alters how rs-FC of this circuit predicts its stress responsiveness. Such changes in pgACC-amygdala functional dynamics may underlie the altered sensitivity to the effects of OXT after ELS.
近期证据表明，早年生活应激（ELS）通过降低杏仁核与前额叶皮质之间的静息态功能连接（rs-FC）来改变应激反应性。催产素（OXT）可调节杏仁核连接并减弱对心理社会应激的反应，但其作用似乎受到ELS的调节。在此，我们首先研究ELS对杏仁核-前额叶rs-FC的影响，并检查该神经回路中与ELS相关的rs-FC变化是否能预测其对心理社会应激的反应。其次，我们探讨OXT和ELS对杏仁核-前额叶回路的联合作用。18名健康年轻男性参与了一项使用双盲、随机、安慰剂对照、受试者内交叉设计的关于OXT作用的静息态功能磁共振成像（fMRI）研究。我们测量了双侧杏仁核的rs-FC，随后评估了状态焦虑的变化以及前额叶对心理社会应激的反应。多元线性回归显示，ELS，特别是情感虐待，可预测右侧杏仁核与膝前扣带回皮质（pgACC）之间的rs-FC降低，这反过来又可预测心理社会应激后状态焦虑的升高。在ELS得分较低的受试者中，较强的pgACC-杏仁核rs-FC可预测在心理社会应激任务期间较强的pgACC失活，并且这种静息-任务交互作用被OXT减弱。然而，在ELS得分较高的受试者中，静息-任务交互作用发生改变，且OXT未显示出显著作用。这些发现突出表明，ELS会降低pgACC-杏仁核rs-FC，并改变该回路的rs-FC对其应激反应性的预测方式。pgACC-杏仁核功能动力学的这种变化可能是ELS后对OXT作用的敏感性改变的基础。
