Cacciaglia Raffaele, Nees Frauke, Grimm Oliver, Ridder Stephanie, Pohlack Sebastian T, Diener Slawomira J, Liebscher Claudia, Flor Herta
Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, 68159 Mannheim, Germany; Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Passeig de la vall d'Hebron 171, Barcelona, Catalonia, Spain.
Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, 68159 Mannheim, Germany.
Psychoneuroendocrinology. 2017 Feb;76:19-28. doi: 10.1016/j.psyneuen.2016.11.012. Epub 2016 Nov 11.
Stress exposure causes a structural reorganization in neurons of the amygdala. In particular, animal models have repeatedly shown that both acute and chronic stress induce neuronal hypertrophy and volumetric increase in the lateral and basolateral nuclei of amygdala. These effects are visible on the behavioral level, where stress enhances anxiety behaviors and provokes greater fear learning. We assessed stress and anxiety levels in a group of 18 healthy human trauma-exposed individuals (TR group) compared to 18 non-exposed matched controls (HC group), and related these measurements to amygdala volume. Traumas included unexpected adverse experiences such as vehicle accidents or sudden loss of a loved one. As a measure of aversive learning, we implemented a cued fear conditioning paradigm. Additionally, to provide a biological marker of chronic stress, we measured the sensitivity of the hypothalamus-pituitary-adrenal (HPA) axis using a dexamethasone suppression test. Compared to the HC, the TR group showed significantly higher levels of chronic stress, current stress and trait anxiety, as well as increased volume of the left amygdala. Specifically, we observed a focal enlargement in its lateral portion, in line with previous animal data. Compared to HC, the TR group also showed enhanced late acquisition of conditioned fear and deficient extinction learning, as well as salivary cortisol hypo-suppression to dexamethasone. Left amygdala volumes positively correlated with suppressed morning salivary cortisol. Our results indicate differences in trauma-exposed individuals which resemble those previously reported in animals exposed to stress and in patients with post-traumatic stress disorder and depression. These data provide new insights into the mechanisms through which traumatic stress might prompt vulnerability for psychopathology.
应激暴露会导致杏仁核神经元发生结构重组。具体而言，动物模型反复表明，急性和慢性应激均会诱导杏仁核外侧核和基底外侧核的神经元肥大及体积增加。这些效应在行为层面上是可见的，应激会增强焦虑行为并引发更强的恐惧学习。我们评估了一组18名有过创伤经历的健康个体（TR组）与18名未接触创伤的匹配对照组（HC组）的应激和焦虑水平，并将这些测量结果与杏仁核体积相关联。创伤包括意外的不良经历，如车祸或亲人突然离世。作为厌恶学习的一种测量方法，我们实施了线索恐惧条件反射范式。此外，为了提供慢性应激的生物学标志物，我们使用地塞米松抑制试验测量了下丘脑 - 垂体 - 肾上腺（HPA）轴的敏感性。与HC组相比，TR组表现出显著更高水平的慢性应激、当前应激和特质焦虑，以及左侧杏仁核体积增加。具体而言，我们观察到其外侧部分有局灶性增大，这与先前的动物数据一致。与HC组相比，TR组还表现出条件性恐惧的晚期习得增强和消退学习缺陷，以及唾液皮质醇对地塞米松的低抑制。左侧杏仁核体积与早晨唾液皮质醇抑制呈正相关。我们的结果表明，有过创伤经历的个体存在差异，这些差异类似于先前在遭受应激的动物以及创伤后应激障碍和抑郁症患者中所报道的差异。这些数据为创伤性应激可能促使心理病理学易感性的机制提供了新的见解。
