An Integrative Examination of Brain Structure and Function in Major Depression

重度抑郁症患者大脑结构和功能的综合检查

• 批准号: 7908937
• 负责人: LARA C FOLAND-ROSS
• 金额: $ 4.56万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2013-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7908937
• 关键词: Address; Affect; American; Amygdaloid structure; Brain; Characteristics; Clinical assessments; Collection; DNA; Data; Depressed mood; Diagnosis; Disease; Dorsal; Emotions; Event; Functional Magnetic Resonance Imaging; Future; Genes; Genetic; Genetic Polymorphism; Genotype; Glucocorticoids; Goals; Hormones; Hydrocortisone; Individual; Intervention; Laboratories; Literature; Magnetic Resonance Imaging; Major Depressive Disorder; Measurement; Measures; Mental Depression; Mental disorders; Methodology; Moods; Neurobiology; Neurosecretory Systems; Participant; Patient Self-Report; Patients; Performance; Population; Predisposition; Prefrontal Cortex; Process; Recording of previous events; Regulation; Reporting; Research; Research Personnel; Salivary; Signal Transduction; Stress; Structure; Surface; Thick; Training; Trauma; base; executive function; gray matter; hypothalamic-pituitary-adrenal axis; neuroimaging; neurotoxic; programs; psychologic; public health relevance; research study; serotonin transporter; tool

DESCRIPTION (provided by applicant): Major Depressive Disorder (MDD) is among the most prevalent of psychiatric disorders, affecting as many as 20% of the American population. Yet, the neurobiologic basis of this disorder has not been elucidated. Structural neuroimaging studies of depressed individuals have documented neuroanatomic abnormalities in subgenual prefrontal cortex (PFC), dorsal PFC, and amygdala, known components of emotion regulatory networks. Findings from this literature, however, are mixed, with some, but not all investigators reporting volumetric reductions in these structures. Further, it is possible that these abnormalities may relate to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, a neuroendocrine system that, when hyper- reactive as in MDD, results in high and likely neurotoxic levels of the glucocorticoid hormone, cortisol. The goal of this research is to assess abnormalities in brain structure and function in individuals diagnosed with MDD using structural MRI in conjunction with self-report measures, functional neuroimaging assessments, indicators of HPA-axis reactivity, and genotyping. Specific goals include (1) assessing whether there are regionally specific neuroanatomic abnormalities in MDD patients using newly developed tools for measuring gray matter thickness; and (2) examining associations among disease-specific alterations in brain structure, HPA-axis dysregulation, and activation level of the amygdala, a limbic structure that receives direct inhibitory cortical input. To achieve these objectives, all participants will undergo functional and structural neuroimaging. Structural MRI data will be processed to provide thickness measurements of cortical gray matter at each point along the cortical surface. To assess HPA-axis reactivity, salivary cortisol levels will be measured during the performance on a laboratory stress task. The association between cortical gray matter thickness and cortisol will be examined at each point along the cortical surface to assess whether structural integrity of cortical regions is, in part, dependent on HPA-axis dysregulation and, thus, whether it is related to susceptibility to becoming frequently hypercortisolemic. Additional analyses examining whether the interaction of brain structure and neuroendocrine function is influenced by genetic (serotonin transporter gene polymorphisms) and environmental (history of trauma) factors will be conducted using salivary DNA and self-report measures. Finally, to examine whether heightened amygdala activation in MDD individuals is related to cortical thickness, fMRI data will be processed to provide percent signal change in this region for use as a covariate for linkage with local gray matter distribution. Negative associations between these measures will be examined, and analyses will address whether regulation of the amygdala, and in a broader sense affect, is dependent on prefrontal gray matter integrity and on the inhibitory/executive functions that this prefrontal region subserves. This program of research will provide the applicant with training in several new methodologies, including the collection and interpretation of genetic, neuroendocrine, and event-related fMRI data, as well as in the diagnosis and clinical assessment of MDD. PUBLIC HEALTH RELEVANCE: Results from the proposed experiments will help to advance our understanding of the neurobiological characteristics of MDD, to elucidate the structural and functional brain abnormalities that are associated with MDD, and to identify phenotypic brain abnormalities that may predispose individuals to extreme labilities in mood. These findings will also serve to inform future projects examining the emergence of these abnormalities in depression, their progression, and the impact of various pharmacological and psychological interventions for MDD.

描述（由申请人提供）： 重度抑郁症（MDD）是最普遍的精神疾病，影响了美国人群的20％。然而，尚未阐明这种疾病的神经生物学基础。抑郁个体的结构性神经影像学研究证明了亚属前额叶皮层（PFC），背部PFC和杏仁核的神经解剖异常，这是情绪调节网络的已知组成部分。然而，这些文献的发现是混合的，有些但并非所有研究人员都报告了这些结构中的体积减少。此外，这些异常可能与下丘脑 - 肾上腺肾上腺（HPA）轴的失调有关，这是一种神经内分泌系统，当像MDD中的过度反应性时，它会导致高且可能的神经毒性水平的糖皮质激素激素，皮质醇，皮质醇。这项研究的目的是评估使用结构MRI与自我报告措施，功能性神经成像评估，HPA轴反应性指标和基因分型的指标，评估使用结构MRI诊断为MDD的个体的异常和功能。具体目标包括（1）评估MDD患者使用新开发的工具来测量灰质厚度的MDD患者中是否存在特定区域特定的神经解剖异常； （2）检查大脑结构，HPA轴失调和杏仁核的激活水平的疾病特异性变化之间的关联，杏仁核是一种接收直接抑制性皮质输入的边缘结构。为了实现这些目标，所有参与者都将经历功能和结构性神经影像学。将处理结构MRI数据，以提供沿皮质表面的每个点的皮质灰质的厚度测量。为了评估HPA轴反应性，在实验室压力任务的性能期间将测量唾液皮质醇水平。皮质灰质厚度和皮质醇之间的关联将在每个点沿皮质表面进行检查，以评估皮质区域的结构完整性是否部分取决于HPA轴功能障碍，因此，它是否与经常变得过度溶性的易感性有关。进一步的分析研究了大脑结构和神经内分泌功能的相互作用是否受遗传（5-羟色胺转运蛋白转运蛋白基因多态性）和环境（创伤史）的影响，将使用唾液DNA和自我报告测量进行。最后，为了检查MDD个体中杏仁核激活是否与皮质厚度有关，将处理fMRI数据以提供该区域的信号变化百分比，以用作与局部灰质分布链接的协变量。将检查这些度量之间的负相关，分析将解决杏仁核的调节以及更广泛的意义上的调节是否取决于前额叶灰质的完整性以及该前额叶区域子服务的抑制/执行功能。该研究计划将为申请人提供几种新方法的培训，包括遗传，神经内分泌和与事件相关的fMRI数据的收集和解释，以及MDD的诊断和临床评估。 公共卫生相关性： 拟议的实验的结果将有助于提高我们对MDD神经生物学特征的理解，以阐明与MDD相关的结构和功能性脑异常，并识别表型脑异常，这些异常可能使个体倾向于情绪极端实力。这些发现还将为未来的项目提供信息，以研究抑郁症中这些异常的出现，它们的进展以及各种药理和心理干预对MDD的影响。