HPA & Emotional Information Processing in Depression

描述（由申请人提供）：数十年来，人们一直在研究重度抑郁症（MDD）患者下丘脑垂体肾上腺（HPA）功能的改变。然而，关于皮质醇在MDD心理特征中的作用知之甚少。广泛的基础研究表明，皮质醇调节核心情感和认知过程（特别是学习和记忆）及其神经基质。到目前为止，很少有临床研究将这些基础知识应用于抑郁症认知和情感的神经基础研究。抑郁症的HPA改变通常以负反馈不足为特征，其中皮质醇升高在抑制HPA进一步激活方面相对无效。来自许多来源的研究表明，在抑郁症患者中，某些关键区域的大脑糖皮质激素受体（GR）可能对皮质醇的影响相对不敏感。该项目将使用皮质醇的药理学操作结合功能性磁共振成像（fMRI）来确定皮质醇对抑郁和健康个体的区域大脑活动的影响是否不同，以及这些对大脑功能的影响如何介导皮质醇对心理功能和HPA负反馈的影响。此外，在抑郁症和健康个体中使用GR的药理学阻断，拟议的项目将测试皮质醇的影响是否由GR介导。候选人是临床心理学家，并在1）MDD区域脑功能的正电子发射断层扫描研究和2）皮质醇对健康个体记忆的影响方面具有研究背景。候选人提出了一个培训计划，其中包括实施拟议的研究计划，这需要在以下各个领域进行培训：深入HPA轴生物学，皮质类固醇受体生物学，临床样本中皮质类固醇功能的药理学探针，药理学功能磁共振成像，以及专业发展和领导技能。

DESCRIPTION (provided by applicant): Alterations in hypothalamic pituitary adrenal (HPA) functioning in Major Depressive Disorder (MDD) have been studied for decades. However, relatively little is known about the role of cortisol in psychological features of MDD. Extensive basic research shows that cortisol modulates core affective and cognitive processes (especially learning and memory) and their neural substrates. As of yet, little clinical research has applied this basic knowledge to the study of neural underpinnings of cognition and affect in depression. HPA alterations in depression are often characterized by deficient negative feedback, in which cortisol elevations are relatively ineffective in suppressing further HPA activation. Research from a number of sources suggests that in depressed individuals, brain glucocorticoid receptors (GR) in certain key regions may be relatively insensitive to the effects of cortisol. The proposed project will use pharmacological manipulation of cortisol in combination with functional magnetic resonance imaging (fMRI) to determine whether cortisol's effects on regional brain activity differ for depressed and healthy individuals, and how these effects on brain functioning mediate cortisol's effects both on psychological functioning and on HPA negative feedback. Furthermore, using pharmacological blockade of GR in depressed and healthy individuals, the proposed projects will test whether the effects of cortisol are mediated by GR. The candidate is a Clinical Psychologist, and has research background in 1) positron emission tomography studies of regional brain functioning in MDD and 2) the effects of cortisol on memory in healthy individuals. The candidate has proposed a training program that includes implementation of the proposed program of research, which requires training in each of the following areas: in depth HPA axis biology, corticosteroid receptor biology, pharmacological probes of corticosteroid functioning in clinical samples, pharmacological fMRI, and professional development and leadership skills.