fMRI Studies Of Pediatric Mood And Anxiety Disorders

儿科情绪和焦虑症的功能磁共振成像研究

• 批准号: 6824229
• 负责人: Daniel Pine
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6824229
• 关键词: adolescence (12-20); anxiety disorders; attention; behavior test; behavioral /social science research tag; child (0-11); child mental disorders; clinical research; developmental psychology; drug resistance; emotions; fluoxetine; functional magnetic resonance imaging; human subject; human therapy evaluation; limbic system; magnetic resonance imaging; major depression; mental disorder chemotherapy; mood disorders; neural information processing; neurochemistry; neuropsychological tests; neuropsychology; psychopharmacology

Through a series of three protocols, we are using functional magnetic resonance imaging (fMRI) and magnetic resonance imaging spectroscopy (MRS) to examine the effects of pharmacologic treatment on neurocognitive and neurochemical correlates of pediatric mood and anxiety disorders. In one aspect of this project, we are attempting to document deficits in brain systems mediating reward-related processes, attention bias, and emotional memory in pediatric mood and anxiety disorders. In a second aspect of this project, we are examining the effects of pharmacological agents on symptoms of mood and anxiety disorders, including both acute episodes as well as treatment resistant symptoms. In a third, aspect of this project, we are examining the effects of treatment on brain activation using fMRI and neurochemistry using MRS. For the acute treatment study, total of 155 children, adolescents and adults will be recruited, including 45 juveniles with a current anxiety disorder, 60 with current major depression, 25 adolescents with no psychiatric disorder. Additionally, 25 psychiatrically healthy adults will be examined. Before the initiation of treatment, these 155 subjects will be tested using behavioral and fMRI paradigms designed to examine brain regions engaged by attending to and encoding emotionally salient stimuli. After this initial fMRI test, the 105 subjects with depression or an anxiety disorder will be randomized to receive eight weeks of double-blind treatment with fluoxetine or placebo. All 155 subjects will be re-tested after eight-weeks using the same two fMRI paradigms. For the study of treatment resistance, 60 subjects will be treated either with an SSRI plus placebo or an SSRI plus lithium. Another 30 subjects will be treated openly with an SSRI. We will acquire MRS measures of neurochemical compounds in these subjects before and after treatment. Prior neuropsychological studies in children as well as in adults note that mood and anxiety disorders are associated with deficits in attention modulation and emotional memory. Prior imaging studies in healthy adults note that tasks requiring attention modulation or emotional memory engage cortico-limbic brain regions previously implicated in adult mood and anxiety disorders. These regions include the amygdala, ventro-medial prefrontal cortex, cingulate gyrus, and hippocampus. As a result, we hypothesize that fMRI attention modulation and emotional memory paradigms will engage these cortico-limbic brain regions in both psychiatrically healthy and impaired subjects. However, these groups will differ in the degree of cortico-limbic engagement. During the first year of this study, we successfully enrolled 11 patients in this protocol. During the second year of the study, we enrolled another 22 subjects, doubling our recruitment efforts. Each of these subjects received neurocognitive examinations, and a subset received fMRI examinations. Each received standardized assessments of response to treatment. As part of our studies in healthy subjects, we also successfully developed each of the fMRI protocols that will be used in the current project. During the coming year, we will be analyzing data from these fMRI studies, as well as a series of behavioral studies in patient groups. Based on the results of these analyses, we also plan to prepare a number of manuscripts. Beyond these ongoing behavioral and fMRI studies, our group is also involved in various collaborations that have led to analyses of other data sets and reporting of research findings. We list below relevant publications supported in this project during the previous year [1-14].

通过一系列三个方案，我们使用功能磁共振成像（fMRI）和磁共振成像光谱（MRS）来检查药理学治疗对儿科情绪和焦虑症的神经认知和神经化学相关性的影响。在该项目的一个方面，我们正在尝试记录大脑系统中的缺陷，以调解与奖励相关的过程，注意力偏见和小儿情绪和焦虑症中的情绪记忆。在该项目的第二个方面，我们正在研究药理药物对情绪和焦虑症症状的影响，包括急性发作和耐药症状。在该项目的第三个方面，我们正在研究使用fMRI和使用MRS神经化学的治疗对脑激活的影响。对于急性治疗研究，将招募共有155名儿童，青少年和成人，其中包括45名患有焦虑症的少年，60名患有重大抑郁症的少年，25名没有精神病障碍的青少年。此外，将检查25名精神病健康的成年人。在开始治疗之前，将使用旨在通过参与和编码情感显着刺激来检查大脑区域的行为和fMRI范式测试这155名受试者。在这项初步的FMRI测试之后，将随机分配105名患有抑郁症或焦虑症的受试者接受氟西汀或安慰剂的双盲治疗。使用相同的两个fMRI范式八周后，将对所有155名受试者进行重新测试。为了研究耐药性，将用SSRI加安慰剂或SSRI加锂对60名受试者进行治疗。另外30名受试者将用SSRI公开处理。我们将在治疗前后的这些受试者中获得神经化合物的MRS测量。 先前在儿童以及成年人中的神经心理学研究指出，情绪和焦虑症与注意调节和情绪记忆的缺陷有关。在健康成年人中的先前成像研究指出，需要注意调节或情绪记忆的任务与以前有关成人情绪和焦虑症的皮质膜大脑区域与皮质膜膜大脑区域有关。这些区域包括杏仁核，腹膜前额叶皮层，扣带回和海马。结果，我们假设fMRI注意力调节和情绪记忆范例将使这些皮质膜膜大脑区域与精神上健康和受损的受试者相关。但是，这些群体在Cortico-limbic参与程度上会有所不同。在这项研究的第一年，我们成功地招募了11名患者。在研究的第二年，我们又注册了22名受试者，使我们的招聘工作增加了一倍。这些受试者中的每一个都接受了神经认知检查，并接受了FMRI检查。每个人都接受了对治疗反应的标准化评估。作为在健康受试者研究的一部分，我们还成功地开发了当前项目中将使用的每种fMRI方案。在来年，我们将分析来自这些功能磁共振成像研究的数据，以及患者组中的一系列行为研究。根据这些分析的结果，我们还计划准备许多手稿。除了这些正在进行的行为和功能磁共振成像研究之外，我们的小组还参与了各种合作，这些合作导致了对其他数据集的分析和研究结果的报告。我们在上一年[1-14]中列出了该项目支持的相关出版物。