The neuroanatomical basis for the human stress response

描述(由申请人提供)：本小额赠款奖(R03)申请是一项资金申请，以支持Tony Buchanan博士收集有关人类应激反应的神经控制的初步数据所需的研究活动，目的是制定一项关于这一主题的持续研究计划。心理社会压力在许多疾病状态的发展中起着作用。动物研究表明，杏仁核、海马体和前额叶皮质参与了应激反应的控制。人类应激反应的神经控制还不是很清楚；这些项目将研究杏仁核、海马体和前额叶皮质受损的人类的这个问题。我们将测量这些受试者的皮质醇和自主神经指数(血压、心率、心率变异性和呼吸)，以响应Trier社会压力测试，这是一种广泛使用的标准化实验室应激源。我们将通过在独立的、无压力的一天评估皮质醇的每日周期来控制激素功能的潜在基线差异。对立位挑战的反应的测量将控制自主神经系统活动的潜在基线组差异。我们预测，杏仁核、海马体或前额叶皮质受损的受试者，与这些靶区以外的大脑受损的受试者相比，对心理社会压力的反应将减弱。将收集对压力源的认知评估和主观压力评级的测量，以检查潜在的群体在压力源感知上的差异。我们预测，应激反应的群体差异不是由于基线的生理功能，而是由于对心理社会应激的不同主观和/或生理反应。精神障碍，如抑郁症和创伤后应激障碍，以杏仁核、海马体和前额叶皮质障碍为特征。这些疾病也与应激生理的改变有关。更好地了解这些神经结构在应激反应中的作用可以增加我们对应激在精神疾病发展中的作用的理解，并有可能开发这些疾病的治疗方法。这项工作是对脑损伤受试者研究的新扩展，结合了神经内科患者登记的优势，提供了无与伦比的局灶性脑损伤患者登记和首席研究员在应激研究方面的专业知识。

DESCRIPTION (provided by applicant): This Small Grant Award (R03) Application is a request for funding to support the research activities necessary for Tony Buchanan, Ph.D. to collect preliminary data on the neural control of the human stress response, with the goal of developing an ongoing research program on this topic. Psychosocial stress plays a role in the development of many disease states. Animal research has implicated the amygdala, hippocampus, and prefrontal cortex in the control of the stress response. The neural control of the human stress response is not well understood; these projects will examine this issue in humans with damage to the amygdala, hippocampus, and prefrontal cortex. We will measure cortisol and autonomic indices (blood pressure, heart rate, heart rate variability, and respiration) of stress in these subjects in response to the Trier Social Stress Test, a widely used and standardized laboratory stressor. We will control for potential baseline differences in hormonal function by assessing the diurnal cycle of cortisol on a separate, stress free day. Measurement of responses to an orthostatic challenge will control for potential baseline group differences in autonomic nervous system activity. We predict that subjects with damage to the amygdala, hippocampus, or prefrontal cortex will show a diminished response to psychosocial stress compared to subjects with brain damage outside these target areas. Measures of cognitive appraisal of the stressor and subjective stress ratings will be collected to examine potential group differences in the perception of the stressor. We predict that group differences in stress responses are not due to baseline physiological functioning, but to differential subjective and/or physiological responses to psychosocial stress. Psychiatric disorders such as depression and posttraumatic stress disorder are characterized by disturbance in the amygdala, hippocampus, and prefrontal cortex. These diseases are also associated with alterations in stress physiology. A better understanding of the role of these neural structures in the stress response could increase our understanding of the role of stress in the development of mental illness with the potential for developing treatments for these diseases. This work is a novel extension of research with brain damaged subjects, incorporating the strengths of the Department of Neurology's Patient Registry, which provides an unequalled registry of patients with focal brain damage and the expertise in stress research of the principal investigator.