Fmri Studies Of Risk For Mood And Anxiety Disorders In Children

Fmri 关于儿童情绪和焦虑障碍风险的研究

• 批准号: 7969343
• 负责人: Daniel Pine
• 金额: $ 90.07万
• 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/7969343
• 关键词: Address; Adolescent; Adult; Amygdaloid structure; Anxiety; Anxiety Disorders; Area; Attention; Behavior; Behavioral; Biological; Brain; Brain region; Child; Childhood; Chronic; Classification; Cognitive; Data; Elderly; Environment; Exhibits; Exposure to; Family; Family Study; Family history of; Foxes; Functional Magnetic Resonance Imaging; Functional disorder; Genes; Genetic; Goals; Hippocampus (Brain); Individual; Infant; Intervention; Investigation; Life; Major Depressive Disorder; Maryland; Medical; Mental disorders; Moods; Neurocognitive; Neurophysiology - biologic function; New York; Paper; Parents; Post-Traumatic Stress Disorders; Prefrontal Cortex; Protocols documentation; Publications; Publishing; Recording of previous events; Recovery; Relative (related person); Research; Resources; Risk; Risk Factors; Sampling; Series; Stimulus; Stress; Structure; Temperament; Testing; Time; Trauma; Universities; Ventral Striatum; Well in self; Work; Youth; base; childhood anxiety; cohort; depressed; design; developmental disease; developmental neurobiology; early childhood; emotion regulation; emotional stimulus; experience; high risk; indexing; infancy; insight; novel; offspring; programs; relating to nervous system; response; social; trend

In this project, our group is examining biological aspects of risk for mood and anxiety disorders in children. Such work has major public impact. By identifying biological risks in children, information on novel treatments and preventative interventions will emerge. Given the understanding of most chronic mental illnesses as developmental disorders, such information holds the hope of dramatically influencing the mental well-being of many individuals. This project encompasses work that is being implemented in three protocols. In one protocol, we are examining the degree to which traumatic experiences predict perturbations in brain function among youth with or without mood or anxiety disorders. In a second protocol, we are examining neurocognitive profiles in a cohort of approximately 350 children and adolescents stratified with respect to personal and family history of mood and anxiety disorders. In a third protocol, we are acquiring fMRI data from a subset of these 350 subjects. Considerable progress has been made during the first five years of work covered in this protocol. However, the amount of work being performed in this protocol has slowed during each of the past two years. The trend continues during the past year. This trend applies both to his protocol specifically over time as well as relative to work being performed in other protocols. This continued trend is because studies of family-risk are quite resource intensive, and insufficient resources are available to maintain all of the ongoing studies on risk. Studies on temperamental risk generally have received more resources than those of family-risk. This trend has also continued, as reflected in research on other protocols performed by the research group. Major questions remain on family-based associations, concerning the degree to which these associations reflect environmental, genetic, or interacting influences of genes and the environment. Moreover, other questions relate to the identification of factors that differentiate among children who are at high risk yet remain resilient from those who are at risk but manifest problems. Work in this project over the next few years is designed to address these questions. Adults with post-traumatic stress disorder (PTSD) or major depressive disorder (MDD) exhibit abnormalities in the structure and function of the amygdala, prefrontal cortex (PFC), and hippocampus. However, while these psychiatric disorders often emerge in childhood, the integrity of these neural structures have been minimally studied in psychiatrically impaired children and adolescents. Work performed in the current protocol has already begun to show that biological correlates of adult mental disorders may manifest quite early in life. In the current proposal on trauma, functional MRI (fMRI) will be used to evaluate the amygdala and the hippocampus in 1) healthy adolescents and those with the following conditions: 2) PTSD; 3) MDD; 4) PTSD and MDD; and 5) abuse without PTSD or MDD. This aspect of the project is actually proceeding relatively slowly. Our group has been able to acquire some data on PTSD and on MDD. We have also published a series of papers on these issues. However, recruitment is generally slow, and we still have yet to demonstrate clear and consistent findings differentiating cognitive and neural functioning in these two groups. Our plan for the coming year is to focus our efforts specifically on studies of temperament, as a risk factor, more than our studies specifically among traumatized indivdiuals. Because we do comprehensively assess stress exposure in all subjects, our studies of temperament should generate insights on the effects of stress in children. Anxiety in children of parents with major depressive disorder (MDD) poses a particularly high risk for later-life MDD. In adults, MDD involves dysfunction in prefrontal brain regions that regulate attention to emotional stimuli. These abnormalities: i) have been found primarily in adults with specific familial forms of MDD; ii) persist after recovery from MDD, and iii) relate to anxiety. These findings raise the possibility that risk for MDD is tied to dysfunction in prefrontal regions involved in regulation of emotion, which possibly manifests as early-life anxiety. If this possibility were confirmed in never-depressed adolescents at high risk for MDD, the findings would provide key insights into the developmental neurobiology of MDD. The goal of this protocol is to study the neural substrate of risk for MDD in young people. This protocol tests the hypothesis that adolescents at high risk for MDD by virtue of childhood anxiety and parental history of MDD exhibit dysfunction in prefrontal cortex and amygdala, regions involved in emotion regulation. This goal will be accomplished through behavioral and fMRI studies of emotion regulation in high and low-risk adolescents. In contrast to our work on trauma, we have made considerable progress in this area. This progress is reflected in a serious of high-impact publications emerging from this work. With respect to our research neurocognitive profiles in offspring of depressed and/or anxious parents, we have acquired data in 225 subjects, working closely with a group from New York University Child Study Center. This includes behavioral data on a face-viewing paradigm that we have also been using to conduct our fMRI studies. Finally, we also continue to maintain a strong collaborative relationship with Dr. Nathan Fox at the University of Maryland. More than the other areas of risk in the current set of studies, these studies with Dr. Fox have received very high priority. Dr. Fox has followed cohorts of approximately 600 infants as they passed though childhood. These children have received repeated assessments of their temperament. Temperament classifications in the sample during infancy and early childhood have been shown to predict behavior later in life. We have also completed an ever-increasing series of investigations in this sample. Results from these studies support the conclusions generated in other research within our group. Namely, this work establishes the presence of strong, consistent associations between the presence of and risk factors for mental illness in children and the presence of perturbed brain function.

在这个项目中，我们的小组正在研究儿童情绪和焦虑症风险的生物学方面。 这种工作具有重大的公众影响。 通过确定儿童的生物学风险，就会出现有关新型治疗和预防干预措施的信息。 鉴于对大多数慢性精神疾病作为发育障碍的理解，这种信息充满希望极大地影响许多人的心理健康。 该项目包括在三个协议中实施的工作。 在一个方案中，我们正在研究创伤经历预测患有或没有情绪或焦虑症的青年人脑功能的扰动程度。 在第二个方案中，我们正在研究大约350名儿童和青少年在情绪和焦虑症的个人和家族史上分层的儿童和青少年的神经认知谱。 在第三个协议中，我们正在从这350个受试者的子集中获取fMRI数据。 在本协议中涵盖的最初五年工作中取得了长足的进步。 但是，在过去两年中，该协议中所做的工作量都放缓了。 在过去的一年中，这种趋势持续了。 这种趋势既适用于他的协议，也适用于随着时间的推移，也适用于其他协议中所做的工作。 这种持续的趋势是因为对家庭风险的研究是相当大的资源密集型，并且资源不足以维持所有正在进行的风险研究。 对气质风险的研究通常比家庭风险更多的资源更多。 这种趋势也持续了，如研究小组执行的其他协议的研究所反映的那样。 关于这些关联反映基因和环境的环境，遗传或相互作用的程度的程度，基于家庭的关联仍然存在主要问题。 此外，其他问题涉及鉴定有高风险却与处于危险中但有明显问题的儿童之间区分的因素有关的因素。 在未来几年中，该项目的工作旨在解决这些问题。 患有创伤后应激障碍（PTSD）或重度抑郁症（MDD）的成年人在杏仁核，前额叶皮层（PFC）和海马的结构和功能中表现出异常。 但是，尽管这些精神疾病经常在童年时期出现，但这些神经结构的完整性在精神科障碍的儿童和青少年中被最少地研究了。 在当前方案中进行的工作已经开始表明，成人精神障碍的生物学相关性可能很早就表现出来。 在当前关于创伤的建议中，功能性MRI（fMRI）将用于评估1）健康青少年和具有以下条件的杏仁核和海马：2）PTSD； 3）MDD; 4）PTSD和MDD； 5）没有PTSD或MDD的滥用。 该项目的这一方面实际上正在相对较慢。 我们的小组能够在PTSD和MDD上获取一些数据。 我们还发表了有关这些问题的一系列论文。 但是，招聘通常很慢，我们仍然尚未证明这两组中的认知和神经功能的明确，一致的发现。 来年的我们的计划是将我们的精力专门集中在气质研究上，这是一种危险因素，而不是在受创伤的非凡者中特别研究。 因为我们确实全面评估了所有受试者的压力暴露，所以我们对气质的研究应产生对儿童压力影响的见解。 患有重度抑郁症（MDD）父母儿童的焦虑对后期MDD的风险特别高。 在成年人中，MDD涉及调节对情绪刺激的注意力的前额叶大脑区域功能障碍。 这些异常：i）主要是在具有特定家族形式的MDD的成年人中发现的； ii）从MDD恢复后持续存在，iii）与焦虑有关。 这些发现提出了一种可能性，即MDD的风险与参与调节情绪调节的前额叶区域的功能障碍相关，这可能表现为早期生活焦虑。 如果在对MDD高风险的永不抑郁的青少年中确认了这种可能性，则这些发现将为MDD的发育神经生物学提供关键的见解。该方案的目的是研究年轻人中MDD风险的神经基质。 该协议检验了以下假设：由于儿童焦虑和MDD的父母历史，在前额叶皮层和杏仁核中表现出功能障碍，涉及情绪调节的地区，MDD的高风险很高。 该目标将通过对高风险和低风险青少年的情绪调节的行为和fMRI研究来实现。 与我们在创伤方面的工作相反，我们在这一领域取得了长足的进步。 这项工作从这项工作中出现了严重的高影响力出版物。 关于我们的研究神经认知概况，在沮丧和/或焦虑的父母的后代中，我们已经获得了225名受试者的数据，并与纽约大学儿童学习中心的一组密切合作。 这包括有关面对观看范式的行为数据，我们也一直使用该范式进行fMRI研究。 最后，我们还继续与马里兰大学的内森·福克斯（Nathan Fox）博士保持牢固的合作关系。 这些与FOX博士的研究相比，在当前研究的其他风险领域中，还获得了很高的优先级。 福克斯博士在童年时期通过了大约600名婴儿的同伙。 这些孩子对自己的气质进行了重复评估。 在婴儿期和幼儿期间样本中的气质分类已被证明可以预测以后的生活行为。 在此样本中，我们还完成了一系列不断增长的调查。 这些研究的结果支持我们小组中其他研究中产生的结论。 也就是说，这项工作确立了儿童精神疾病的存在和危险因素与脑功能的存在之间存在牢固，一致的关联。