应激源伴随着人的一生，长期的严重的应激对正常人的心理生理产生不良影响，甚至会导致创伤后应激障碍（posttraumatic stress disorder, PTSD）。面对应激源时，下丘脑-垂体-肾上腺轴（hypothalamic-pituitary-adrenocortical axis, HPA）被激活，促使肾上腺皮质释放糖皮质激素。除了应激反应外，在人类基础状态下 HPA 轴还有一个昼夜节律，即在清晨醒来时皮质醇分泌达到一个高峰值（即皮质醇觉醒反应，cortisol awakening response，CAR） ，其后全天都处于下降期。目前，慢性应激对 HPA 轴活动的影响的研究很多，但结果并不一致。此外，应激还通过皮质醇对人类的认知过程产生影响。关于慢性应激对脑功能的影响，已有研究主要关注刺激呈现后的信息加工过程。然而，对于环境中出现的各种刺激，我们的大脑并不是被动反应；在刺激呈现前，大脑始终处于一定程度的活跃状态，包括静息状态下和预期刺激即将来临时的脑功能状态。因此，本研究的目的是从不同程度的慢性应激（学业相关慢性应激和PTSD）入手探讨其对神经内分泌的影响，并通过事件相关电位技术（event-related potentials, ERPs）考察不同程度的慢性应激对大脑静息态和期待加工的影响。
研究一以经历长期考试准备作为慢性应激源，考察健康人的慢性应激对神经内分泌和脑功能的影响。研究结果发现， 应激组在应激觉察量表得分和焦虑量表上的得分显著高于控制组；应激组的皮质醇觉醒反应（cortisol awakening response, CAR）显著低于控制组，而且这一效应主要表现在应激组的高应激得分被试身上；对于所有被试而言，应激与焦虑水平与 CAR 有显著的负相关关系。这说明慢性应激可能会导致 CAR 降低，这可能是由于神经内分泌资源长期消耗造成的。从脑功能角度来说，经历慢性应激的人对即将到来的刺激更为期待，表现为应激组比控制组的关联性负变化（contingent negative variation, CNV）波幅变大；此外，对于控制组被试，状态焦虑水平与 CNV波幅大小有显著的正相关关系，而应激组不存在这种相关，表明长期处于慢性应激的个体，期待加工已经处于天花板水平，使得状态焦虑无法再对皮层的兴奋性进行进一步调节。然而，应激组和控制组在静息状态下的皮层偏侧化活动上并没有差异。
研究二以经历过重大灾难性事件（2008年汶川地震）后出现临床创伤后应激生理病理症状的人群为研究对象，考察被诊断为PTSD的患者（PTSD组）和同样经历地震但未达到 PTSD诊断指标的人群（非 PTSD组）在神经内分泌和脑功能上的差异，以及各指标与创伤后应激障碍各个症状簇之间的关系。PTSD 组在做任务时的皮质醇反应与非 PTSD组无差异；对于所有经历过创伤的被试而言，皮质醇反应主要与负性情感维度有显著的正相关关系，但与快感缺失无相关关系。该结果表明对认知任务的期待和执行时高皮质醇水平可能与特定的 PTSD症状簇负性情感有关，并为 PTSD六维模型中将负性情感和快感缺失划分为两个独立的维度提供了一定的神经内分泌学证据。从脑功能角度来说，PTSD 组对即将到来的刺激更为期待，表现为PTSD组比非 PTSD组的CNV波幅更大。 在行为水平上， PTSD组比非 PTSD 组的错误率更高，表明虽然PTSD患者对环境中即将到来的刺激更警觉也更为期待，但其行为绩效仍被削弱。此外，高期待性唤醒还与 PTSD的严重程度以及再体验症状相关，这可能是由于有创伤经历的个体感觉过滤异常所调节的。
Stress is associated with human life. Long-term major stress has adverse influence on people’s psychological and physiological health, even leading to posttraumatic stress disorder (PTSD). When faced with the stressors, the hypothalamic-pituitary-adrenal (HPA) axis is activated, prompting the release of glucocorticoids from the adrenal cortex. In addition to the stress responsiveness, the HPA axis has a circadian rhythm in the human basal condition, which means cortisol secretion reaches highest in the morning upon awakening (i.e., cortisol awakening response, CAR), and subsequently declines all day long. Currently, there are plenty of researches about the effect of chronic stress on HPA axis’s activity and reactivity, yet the results are not consistent. On the other hand, stress also affects human cognition through cortisol. About the impact of chronic stress on brain function, previous research mainly focused on the information processing stage after stimulus presented. However, our brain doesn’t passively respond to the various stimuli in the environment; before the stimulus appears, our brain always maintains an active state in a certain degree, including resting functional state as well as the anticipatory state for the upcoming stimuli. Therefore, the purpose of this study is to explore the effect of chronic stress (academic stress and PTSD) on neuroendocrine as well as brain function (resting state and anticipation process) with the aid of event-related potentials (ERPs).
Study 1 focuses on the effect of chronic stress (long-term exam preparation) of health people on HPA activity and brain function. The results showed that the stress group had greater perceived stress relative to the control group. The cortisol awakening response (CAR) in the stress group were significantly lower than the control group and this effect was most pronounced for participants with high levels of perceived stress in the stress group. Perceived stress and anxiety levels were negatively correlated with CAR. Chronic examination stress can lead to the decrease of CAR in healthy young men, possibly due to cortisol overconsumption under long-term sustained stress. From the perspective of brain function, participants under chronic stress anticipated more to the upcoming events, as demonstrated by the result that the amplitude of contingent negative variation (CNV) was larger in the stress group compared to the control group; furthermore, for the control group, state anxiety was positively related to both the iCNV and lCNV amplitude; however, there was no such relationship in the stress group. These results suggested that the cortical anticipatory activity in the stress group reached the maximum ceiling, leaving little room for transient increases in state anxiety. Nevertheless, there was no difference between the stress and control group on α asymmetry pattern under resting state.
Study 2 mainly focused on the group of population who suffered from severe catastrophic event (2008 Wenchuan earthquake) and showed some clinical symptoms, and explored neuroendocrine reactivity and anticipatory process change between participants who dignosed as PTSD (PTSD group) and non-PTSD group, as well as their relationship with the severity of total posttraumatic symptomology and distinct symptom clusters. There is no difference between PTSD group and non-PTSD group on cortisol level during cognitive tasks; for the whole participants who suffered from the earthquake, higher cortisol levels before and during cognitive tasks are specifically linked to a distinct symptom cluster of PTSD—negative affect symptomatology. This suggests that a distinction should be made between negative affect and anhedonia symptom clusters, as the 6-factor model proposed. From the perspective of brain function, the PTSD group anticipated more to the upcoming events, as demonstrated by the result that compared to the non-PTSD group, the PTSD group had significantly larger CNV amplitude. On the behavioral level, the PTSD group committed more errors than the non-PTSD group, which suggested that individuals with PTSD might be more alerted to and anticipate more to the upcoming events in their environment, yet still have degraded performance in response to the stimulus. Furthermore, the higher anticipatory arousal was associated with more severe global PTSD symptom as well as more severe re-experiencing symptom cluster, which might be mediated by deficient sensory filtering in individuals with trauma experience.