Neural Markers of Individual Difference in Emotion Regulation in Depressed Adults

描述(由申请人提供)：这项拟议的以患者为导向的导师研究职业发展奖(K23)的目的是为候选人提供必要的情感神经科学方面的培训，以检验与抑郁症治疗的个体差异相关的功能神经机制。尽管大量的经验支持证明了几种不同治疗方式的有效性，但没有一种治疗方法对所有患者都同样有效。该奖项的目标是利用功能神经成像技术。 检查抑郁症患者在与不同治疗反应密切相关的个性特定方面存在差异的技术是否也在 情绪调节神经系统的特定自动和自愿组件。这项研究的长期目标是确定可靠的、基于生物学的抑郁症患者个体差异的标记，这可能导致开发更有效的、个性化的治疗方法。候选人在识别与抑郁症治疗的不同反应相关的患者变量方面拥有专业知识。通过拟议的职业发展奖，候选人正在寻求通过学习检查功能神经机制来建立这一技能集，这些机制可能是他和其他人报告的差异治疗反应预测因素的基础。他将通过接受情感和翻译神经科学的三个相关领域的培训来获得这些技能：1)情绪调节和抑郁的神经解剖学功能；2)先进的神经成像技术；3)使用神经成像方法为临床治疗研究提供信息。为了实现这些培训目标，应聘者提议参加四种类型的培训活动：与导师的每周会议和教学、与专家顾问的定向阅读和培训、正式的课程作业和参加科学会议。为了确保候选人实现他的目标，即成为一名独立科学家，能够利用情感神经科学的工具来回答有关治疗反应个体差异背后的机制的重要问题，他组建了一个由导师和顾问组成的专家团队。这些专家中的每一位都有培训初级科学家并将他们培养成成功的独立调查人员的良好记录。这位候选人的导师玛丽·菲利普斯博士和艾伦·弗兰克博士拥有广泛和互补的专业知识。菲利普斯博士是情绪障碍背景下情绪调节功能神经成像方面的专家，弗兰克博士是抑郁症评估和治疗方面的专家。同时，他们的指导将确保候选人成功地实现他的研究和职业发展目标。拟议的研究和培训活动将在匹兹堡大学医学院的精神病学系进行。对于提议的项目来说，这是一个理想的环境。该部门在情感神经科学、人格和抑郁症研究方面有着长期的卓越记录。每个研究领域的资深教员都有代表参加拟议的导师和顾问团队。候选人将在整个拟议的获奖期内获得上述每个研究领域的广泛资源。这项拟议的研究将进一步促进候选人的培训，该研究将检查抑郁症成年人在自动和自愿情绪调节神经系统功能方面的个体差异，这些成年人在与不同治疗反应相关的人格方面表现得很高和很低。这项研究将检查与情绪调节相关的关键前额叶皮质和皮质下区域内和关键区域之间神经活动和连接的功能神经成像测量。神经影像、症状和个性数据将从60名目前患有抑郁症的成年人中获得(30名在感兴趣的人格方面得分较低，30名得分较高)，以及30名精神健康的对照组参与者。这项拟议项目的目的是检查在与不同治疗反应相关的个性方面存在差异的抑郁症患者，是否也在自动和自愿情绪调节神经系统的功能上存在差异。这些神经系统功能的异常将通过以下任务来评估：1)在处理相互冲突的情绪信息时的自动情绪调节；2)在对负面情绪的认知重新评价期间的自愿情绪调节；以及3)在对负面自我信念的认知重新评价期间的自愿情绪调节。建议项目的具体目标与国家精神卫生研究所的战略目标很好地匹配，这项研究的结果有望帮助确定抑郁症患者个体差异的可靠标志。这些发现可能具有巨大的临床实用价值，并可能导致未来的工作，试图完善现有的治疗策略，使其对情绪调节系统功能缺陷的患者更有效。

DESCRIPTION (provided by applicant): The aim of this proposed Mentored Patient-Oriented Research Career Development (K23) Award is to provide the candidate with the training in affective neuroscience necessary to examine the functional neural mechanisms associated with individual differences in response to treatments for depression. Despite abundant empirical support demonstrating the efficacy of several different treatment modalities, no treatment works equally well for all patients. The goal of the proposed award is to utilize functional neuroimaging techniques to examine whether depressed patients who differ on specific facets of personality that are strongly associated with differential treatment response also differ in the functioning of specific automatic and voluntary components of the emotion regulation neural system. The long-term goal of this research is to identify reliable, biologically based markers of individual differences among depressed patients that could lead to the development of more effective, individually tailored treatments. The candidate possesses expertise in the identification of patient variables that are associated with differential response to treatments for depression. Through the proposed career development award, the candidate is seeking to build on this skill set by learning to examine the functional neural mechanisms that may underlie the predictors of differential treatment response that he and others have reported. He will acquire these skills by receiving training in three related areas of affective and translational neuroscience: 1) functiona neuroanatomy of emotion regulation and depression; 2) advanced neuroimaging techniques, and 3) the use of neuroimaging measures to inform clinical treatment research. In order to achieve these training goals, the candidate has proposed to participate in four types of training activities: weekly meetings and didactics with mentors, directed readings and training with expert consultants, formal coursework, and participation in scientific conferences. To ensure that the candidate meets his goal of becoming an independent scientist who can utilize the tools of affective neuroscience to answer important questions about the mechanisms underlying individual differences in treatment response, he has assembled an expert team of mentors and consultants. Each of these experts has a strong record of training junior scientists and fostering their development into successful independent investigators. The candidate's mentors, Drs. Mary Phillips and Ellen Frank, have extensive and complementary sets of expertise. Dr. Phillips is an expert in the functional neuroimaging of emotion regulation in the context of mood disorders, and Dr. Frank is expert in the assessment and treatment of depression. Together, their guidance will ensure that the candidate successfully meets his research and career development goals. The proposed research and training activities will take place in the Department of Psychiatry at the University of Pittsburgh School of Medicine. This is an ideal setting for the proposed project. The department has a longstanding track record of excellence in affective neuroscience, personality, and depression research. Senior faculty from each of these research domains are represented on the proposed mentorship and consultant team. The candidate will have access to extensive resources in each of these research areas throughout the proposed award period. The candidate's training will be further advanced by the proposed study, in which individual differences in the functioning of the automatic and voluntary emotion regulation neural systems will be examined among depressed adults who are high and low on facets of personality associated with differential treatment response. The study will examine functional neuroimaging measures of neural activity and connectivity within and between key prefrontal cortical and subcortical regions associated with emotion regulation. Neuroimaging, symptom, and personality data will be acquired in a sample of 60 currently depressed adults (30 with low scores on the personality facets of interest and 30 with high scores), as well as 30 psychiatrically healthy control participants. The aims of the proposed project are to examine whether depressed patients who differ on the personality facets associated with differential treatment response also differ in the functioning of the automatic and voluntary emotion regulation neural systems. Abnormalities in the functioning of these neural systems will be assessed using tasks that target: 1) automatic emotion regulation during the processing of conflicting emotional information; 2) voluntary emotion regulation during the cognitive reappraisal of negative emotions; and 3) voluntary emotion regulation during the cognitive reappraisal of negative self-beliefs. The specific aims of the proposed project match well with the strategic goals of the National Institute of Mental Health, and the results of this study can b expected to help identify reliable markers of individual difference among patients with depression. These findings could have enormous clinical utility and could lead to future work attempting to refine existing treatment strategies to make them more effective for patients with functional deficits in the emotion regulation system.