The neuroanatomical basis for the human stress response

描述（由申请人提供）：此小额赠款（R 03）申请是一个资金的要求，以支持必要的研究活动托尼布坎南，博士。收集有关人类应激反应的神经控制的初步数据，目的是开发一个正在进行的研究计划。心理社会压力在许多疾病状态的发展中起作用。动物研究表明，杏仁核、海马体和前额叶皮层都参与了压力反应的控制。人类压力反应的神经控制还没有得到很好的理解;这些项目将在杏仁核、海马体和前额皮质受损的人类中研究这个问题。我们将测量皮质醇和自主神经指数（血压，心率，心率变异性和呼吸）的压力在这些科目中的特里尔社会压力测试，广泛使用和标准化的实验室压力。我们将通过在单独的无压力日评估皮质醇的昼夜周期来控制激素功能的潜在基线差异。测量对立位挑战的反应将控制自主神经系统活动的潜在基线组差异。我们预测，与这些目标区域以外的脑损伤受试者相比，杏仁核、海马体或前额皮质受损的受试者对心理社会压力的反应会减弱。将收集压力源的认知评估和主观压力评级的措施，以检查压力源感知的潜在群体差异。我们预测，压力反应的群体差异不是由于基线生理功能，但不同的主观和/或心理社会压力的生理反应。精神疾病如抑郁症和创伤后应激障碍的特征是杏仁核、海马体和前额皮质的紊乱。这些疾病也与应激生理学的改变有关。更好地了解这些神经结构在压力反应中的作用，可以增加我们对压力在精神疾病发展中的作用的理解，并有可能为这些疾病开发治疗方法。这项工作是一个新的扩展研究与脑损伤的主题，结合神经科的病人登记处，它提供了一个无与伦比的登记局灶性脑损伤和压力研究的主要研究者的专业知识的部门的优势。

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.