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Translational Neuroimaging in Unipolar Depression: Towards Personalized Treatment

单相抑郁症的转化神经影像学：走向个性化治疗

基本信息

批准号：
8269110
负责人：
GREG J SIEGLE
金额：
$ 11.85万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-08-01 至 2013-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8269110
关键词：
Accounting Address Adult Affect Age Algorithms Amygdaloid structure Antidepressive Agents Anxiety Area Attention Award Basic Science Behavior Therapy Behavioral Biological Factors Brain Brain region Clinic Clinical Clinical Trials Clinical assessments Cognitive Cognitive Therapy Collaborations Computer Simulation Data Data Collection Depressed mood Development Disease Elderly Emotional Emotions Environment Evaluation Exercise Flowers Functional Imaging Functional Magnetic Resonance Imaging Funding Heterogeneity Independent Scientist Award Individual Individual Differences Institutes Intervention Investigation Lateral Lead Left Longevity Mental Depression Mentored Research Scientist Development Award Methods Mydriasis Neurophysiology - biologic function Neurosciences Outcome Patients Peripheral Pharmaceutical Preparations Physiological Population Prefrontal Cortex Process Proxy Psychologist Psychophysiology Recovery Research Research Personnel Role Sampling Science Seeds Silk Stimulus Supervision System Testing Time Training Translating Translational Research Translations Unipolar Depression Vision Work Youth base cognitive control conventional therapy depressive symptoms design emotion regulation emotional stimulus executive function geriatric depression high standard improved information processing insight middle age mild neurocognitive impairment neuroimaging neuromechanism novel preconditioning prevent relating to nervous system response service intervention therapy development treatment planning treatment response vigilance

项目摘要

DESCRIPTION (provided by applicant): The best first-line treatments work for approximately 40-60% of unipolar depressed adults, potentially due to the disorder's complexity and heterogeneity. Basic research on the neural mechanisms of depression, assessed using functional neuroimaging has blossomed in the past decade. The proposed research will combine neuroimaging, behavioral/psychophysiological assessment, and clinical trials to allow rigorous translation of this basic science to the clinic. This work will help to direct patients specifically to treatments that will address their particular mechanisms and could lead to the development of novel neuroscience-based interventions. Such translational research has been done almost exclusively in mid-life adults. Yet, attention has increasingly focused on the extent to which interventions that address relevant brain mechanisms in mid-life individuals (e.g., Cognitive Behavioral Therapy, SSRI's) might be useful with vulnerable or depressed youth and elderly depressed individuals. Increasing research suggests that the same mechanisms which are disrupted in mid-life depression, and which are targeted in therapy, such as increased limbic response to emotional stimuli, are present in anxious youth (Easter et al 2005) who are vulnerable to depression, and may further predict treatment response in these individuals (McClure et al in press-a). Similarly, hallmarks of dysregulated emotion in depression which predict treatment response in mid-life individuals such as decreased prefrontal function are present in a high proportion of elderly depressed adults (e.g., Alexopoulos et al., 2000) and may thus be as, or more important to address in planning treatments in that population. Thus, a life-span developmental perspective will be a key generalization of ongoing translational neuroimaging research. Dr. Siegle is uniquely poised to make significant advances in this type of translational research. Following his training as a clinical psychologist and cognitive neuroscientist, his K01 award yielded computational modeling and neuroimaging data that lead to specific predictions about recovery from depression. Western Psychiatric Institute and Clinic provides a highly collaborative clinical trials environment, allowing him to test these hypotheses. His R01 has begun this work, adding assessments to existing clinical trials and collaborating with established clinical trials researchers. To continue his clinical translations to the high standards of his basic research, Dr. Siegle proposes to receive additional training and supervision in the design, execution, and evaluation of clinical trials for conventional and novel interventions. In addition, Dr. Siegle's research has focused on mid-life depressed individuals, but is increasingly being applied to understanding clinical outcomes in youth and late-life individuals. Obtaining training in potential issues associated with generalizing to the entire lifespan will be important for allowing him to advise such translations.

描述（由申请人提供）：最好的一线治疗方法对大约40-60%的单极抑郁症成年人有效，这可能是由于该疾病的复杂性和异质性。在过去的十年里，对抑郁症的神经机制的基础研究，利用功能性神经成像进行评估，已经蓬勃发展。拟议的研究将结合神经影像学、行为/心理生理学评估和临床试验，以使这一基础科学严格转化为临床。这项工作将有助于指导患者进行专门的治疗，以解决他们的特殊机制，并可能导致新的基于神经科学的干预措施的发展。这种转化研究几乎都是在中年成年人身上进行的。然而，越来越多的注意力集中在中年人的相关大脑机制的干预措施（例如，认知行为疗法，SSRI）可能对脆弱或抑郁的青年和老年抑郁症患者有用的程度上。越来越多的研究表明，同样的机制在中年抑郁症中被破坏，并且是治疗的目标，例如对情绪刺激的边缘反应增加，在易患抑郁症的焦虑青年中也存在（easteret al . 2005），并且可能进一步预测这些个体的治疗反应（McClure et al . in press-a）。同样，抑郁症中情绪失调的特征可以预测中年个体的治疗反应，如前额叶功能下降，这在老年抑郁症成年人中也有很高的比例（例如，Alexopoulos等人，2000），因此，在该人群的治疗计划中，这可能是同样重要的，或者更重要的。因此，一生发育的观点将是正在进行的转化神经影像学研究的关键概括。西格尔博士在这种类型的转化研究中取得了重大进展。在接受临床心理学家和认知神经科学家的培训后，他获得了K01奖，获得了计算建模和神经成像数据，这些数据有助于预测抑郁症的康复。西方精神病学研究所和诊所提供了一个高度协作的临床试验环境，使他能够测试这些假设。他的R01已经开始了这项工作，增加了对现有临床试验的评估，并与已建立的临床试验研究人员合作。为了继续将他的临床研究转化为高标准的基础研究，Siegle博士建议接受额外的培训和监督，以设计、执行和评估传统和新型干预措施的临床试验。此外，西格尔博士的研究主要集中在中年抑郁症患者身上，但也越来越多地应用于了解青年和老年患者的临床结果。获得与推广到整个生命周期相关的潜在问题的培训对于允许他为此类翻译提供建议非常重要。

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Looking under the hood of the dot-probe task: an fMRI study in anxious youth.

DOI：
10.1002/da.22255
发表时间：
2014-03
期刊：
DEPRESSION AND ANXIETY
影响因子：
7.4
作者：
Price, Rebecca B.;Siegle, Greg J.;Silk, Jennifer S.;Ladouceur, Cecile D.;McFarland, Ashley;Dahl, Ronald E.;Ryan, Neal D.
通讯作者：
Ryan, Neal D.

Integration of neuroimaging into clinical pediatric psychiatry?

将神经影像学纳入临床儿科精神病学？