NEUROBIOLOGICAL BASIS OF DEPRESSION AFTER BRAIN DAMAGE

脑损伤后抑郁的神经生物学基础

• 批准号: 6391626
• 负责人: ANA SOLODKIN
• 金额: $ 11.45万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-15 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6391626
• 关键词: astrocytes; bioimaging /biomedical imaging; cell death; cerebral ischemia /hypoxia; clinical depression; clinical research; comorbidity; dendrites; dopamine; functional ability; functional magnetic resonance imaging; human subject; human tissue; immunocytochemistry; motor cortex; neural plasticity; neurochemistry; neuropathology; norepinephrine; oligodendroglia; postmortem; psychomotor function; serotonin; stroke

Depression is a serious complication of structural brain injury, and can severely impair physical and cognitive recovery. Of the three million stroke survivors living in the US, more than 65 percent of them will suffer clinical symptoms of depression. Many of these cases can be directly attributable to the stroke, making post-stroke depression a serious health problem. The specific aim of this proposal is to study the biological bases of depression as revealed through patients recovering from ischemic focal brain injury. These studies of depression will focus on its effects on motor system plasticity after middle cerebral artery infarction. We will test the following hypotheses: Motor cortices in clinically depressed subjects will present neurochemical changes in monoaminergic systems (Serotonin, dopamine and noradrenaline). Recovery of motor skills after frontal ischemic stroke depends on the anatomical reorganization of ipsilateral frontal regions adjacent to the infarcted area, and these anatomical changes will be more pronounced in individuals without depression when compared to cases with post-stroke depression. Functional neuroimaging will corroborate the anatomical findings, demonstrating poorer anatomical recovery in depressed patients than in those without depression. Areas underlying functional recovery as seen with fMRI will show the greatest degree of anatomical reorganization when assessed with direct anatomical methods in non-depressed cases compared to depressed ones. The overriding goal of this research is to investigate the neuroanatomical and neuropharmacological differences between depressed and non-depressed patients following focal ishemic brain damage, and to correlate the findings from studies of autopsy tissue with neuroimaging studies using functional magnetic resonance imaging (fMRI). Since combining both methods will limit the number of cases, in parallel, we will perform the same neuroantomical studies in post-mortem tissue with damage in the equivalent areas (but without fMRI assessment). The detection of the changes in cellular circuitry during recovery in groups with and without post-stroke depression will allow us to understand better the neurobiological substrate of this disorder. In the long run, this information may lead to novel pharmacological treatments in both depression and stroke, but most importantly, in those cases where depression is a concomitant of structural brain injury. At the same time, the current research aims to give the principal investigator necessary mentored experience to achieve independence in biological psychiatry research.

抑郁症是结构性脑损伤的严重并发症，可严重损害身体和认知的恢复。在生活在美国的300万中风幸存者中，超过65%的人将出现抑郁症的临床症状。其中许多病例可以直接归因于中风，使中风后抑郁成为一个严重的健康问题。这项建议的具体目的是研究从缺血性局灶性脑损伤中恢复的患者中揭示的抑郁症的生物学基础。这些关于抑郁的研究将集中在它对大脑中动脉梗死后运动系统可塑性的影响。我们将检验以下假设：临床抑郁症受试者的运动皮质将在单胺能系统(5-羟色胺、多巴胺和去甲肾上腺素)中呈现神经化学变化。额叶缺血性卒中后运动技能的恢复有赖于梗死区附近同侧额叶区域的解剖重组，与卒中后抑郁的患者相比，无抑郁者的这些解剖学改变更为明显。功能神经成像将证实解剖学发现，显示抑郁症患者的解剖恢复比没有抑郁症的患者更差。与抑郁症患者相比，在非抑郁症患者中使用直接解剖学方法进行评估时，功能磁共振成像显示的潜在功能恢复区域的解剖重组程度最大。这项研究的首要目标是调查局灶性脑缺血损伤后抑郁和非抑郁患者之间的神经解剖学和神经药理学差异，并将尸检组织研究的结果与使用功能磁共振成像(FMRI)的神经成像研究相关联。由于这两种方法的结合将限制病例的数量，同时，我们将在死后组织中进行相同的神经自发性研究，并在同等区域内进行损伤(但不进行功能磁共振评估)。检测中风后抑郁患者和非中风后抑郁患者在康复过程中细胞回路的变化将使我们更好地了解这种疾病的神经生物学基础。从长远来看，这些信息可能会为抑郁症和中风带来新的药物治疗方法，但最重要的是，在抑郁症与结构性脑损伤相伴的情况下。同时，本研究旨在给予首席研究者必要的指导经验，以实现生物精神病学研究的独立性。