Daily And Chronic Stress Decreased HPA Axis Reactivity To Acute Stress:The Neural Modulation Effect Of Hippocampus

Stress refers to the process of a series of physiological,psychological and behavioral adaptive responses when individuals face actual or imagined psychological challenges or threats to cope with internal and external challenges and maintain homeostasis.The hypothalamic-pituitary-adrenal axis(HPA axis)is an important physiological manifestation in the individual stress response,and its activation can promote the reconfiguration of resources in the organism to achieve adaptation to the external environment.Individuals will experience various stressors in the social living environment.Studies have found that the individual’s physiological stress response will be affected by factors such as previous stress experience,thus showing individual differences in stress regulation.Long-term,continuous stress exposure decreases the acute stress response of the HPA axis,and daily stress events on a shorter time scale also decreases the acute stress response of the HPA axis.The brain is the core organ for threat perception,cognitive evaluation,and stress regulation.The hippocampus is an important brain region that regulates the HPA axis.However,few studies have explored the neural basis of the decreased acute stress response of the HPA axis.Based on this,in Study 1,college students were asked to fill out the daily stress questionnaire to review the stress exposure status within 24 hours,and then scanned the resting state,followed by inducing their acute stress through high cognitive load accompanied by social evaluation threat.During the experiment,five saliva samples were collected to analyze cortisol concentrations as an indicator of acute stress response.It was found that daily stress levels were significantly negatively correlated with salivary cortisol responses and significantly positively correlated with subjective stress responses,and hippocampal regional homogeneity(Re Ho)could mediate the negative relationship between daily stress levels and acute salivary cortisol responses.In Study 2,participants were scanned in the task state(acute stress task).During the experiment,saliva samples were collected five times to analyze the concentration of cortisol as an indicator of acute stress response,and hair samples were collected to analyze hair cortisol concentration in the last month as an indicator of chronic stress exposure.It was found that the hair cortisol concentration was positively correlated with the subjective stress response marginally,and not correlated with the salivary cortisol response,but the hippocampal activation level during the stress condition could moderate the relationship between the hair cortisol concentration and the salivary cortisol response.The results of the two studies support that the phenomenon of decreasing the HPA axis response is not the body’s successful adaptation to acute stressors,but the objective maladaptation caused by insufficient cortisol secretion when exposed to acute stressors.Importantly,the hippocampus plays an important role in the attenuation of the acute stress response of the HPA axis.Both the spontaneous activity in the resting state and the brain activity when encountering stress events show inhibition and impairment.There are also differences in the attenuating effects of daily stress and chronic stress.The attenuating effect of chronic stress may not be directly observed while the attenuating effect of daily stress can be observed directly.One possibility of this difference is that when measuring the intensity of chronic stress in healthy individuals,due to insufficient exposure intensity or average effect,it cannot directly reach statistical significance.Another possibility is that the two are different phenomena with different mechanisms.The attenuating effect of chronic stress may be consistent with the hypothesis of allostasis.The HPA axis has a process of transition from high reactivity to low reactivity,but there is no development track of response transition in daily stress.This study extends the causal timescales of HPA axis attenuation and provides some neural basis for the attenuation response,highlighting the role of the hippocampus.The exploration of the attenuation phenomenon is not only conducive to deepening the understanding of individual differences in the acute stress response of the HPA axis,but also has a certain degree of contribution to the prevention of stress-related diseases in the future.Future research can intervene in the hippocampus in various ways to alleviate HPA axis dysregulation.