Prefrontal Mechanisms of Selection: Disrupted in Internalizing Psychopathology?

 描述(申请人提供)：青春期是一个重要的发育期，其特征是多个领域的快速变化，包括大脑前额叶皮质的成熟，计划和认知控制的增加，以及焦虑和抑郁的发生率大幅增加。控制和计划方面的缺陷已被确定为精神疾病的风险因素，包括抑郁和焦虑。控制的一个方面还没有被研究，但可能会影响抑郁和焦虑的风险，那就是在计划或努力实现目标时，快速有效地在相互竞争的选项中进行选择的能力。这样的选择对任何人来说都可能是困难的，但对于焦虑或抑郁水平升高的个人来说尤其困难，这会导致规划和决策方面的问题。到目前为止，这些问题主要是在成年人身上研究的。然而，了解这些能力是如何在青春期发展起来的很重要，因为青春期是精神疾病许多方面首次出现的发育期。这项拟议的研究建立在一个创新和综合的模型之上，该模型说明了这种选择能力是如何实现的。它在多个分析单元中研究了这个问题，将a)大脑的神经化学，b)特定Brin区域的激活，c)在需要选择的任务中的行为表现联系起来d)自我报告能力 在日常生活中进行选择。这项提议汇集了一个多学科的科学家团队，他们在成年人(认知和发育神经科学家，以及一名在脑成像方面有专长的物理学家)中阐述并测试了原始模型，以及一名在青春期焦虑和抑郁发展方面有专长的临床科学家。该项目利用了高度保留的青年及其照顾者样本，这些青年及其照顾者前瞻性地接受了5年的广泛精神病理学评估，但以前从未接受过神经成像或规划或控制评估。该项目将在最初的时间点和两年后对144名青年(72名中青年和72名年龄较大的青少年)和72名成年人进行测试。本项目旨在确定青春期和成年期选择的生物行为机制的发展(目标1)，选择机制与焦虑和抑郁之间的联系(目标2)，以及这些选择机制如何随着时间的推移预测精神病理学的变化(目标3)。这项拟议的研究将通过提供有关青春期发展的重要过程以及它们与精神疾病发病的关系的信息，产生重大的创新影响。该项目提供的数据将有助于开辟新的领域，促进该领域对青春期关键时期控制和规划与心理健康相互作用方面的发展变化的理解。

 DESCRIPTION (provided by applicant): Adolescence is an important developmental period characterized by rapid changes in multiple domains, including maturation of the brain's prefrontal cortex, increases in planning and cognitive control, and also a large increase in rates of anxiety and depression. Deficits in control and planning have been identified as a risk factor for mental illness, including depression and anxiety. One aspect of control that is understudied but likely affects risk for depression and anxiety, is the ability to quickly and efficiently selec among competing options when planning or working towards a goal. Such selection can be difficult for anyone, but is especially so for individuals with elevated levels of anxiety or depression, leading to problems in planning and decision-making. To date, these issues have primarily been studied in adults. However, it is important to understand how these abilities develop during adolescence because that is the developmental time period in which many aspects of mental illness first appear. The proposed research builds upon an innovative and integrative model of how such selection abilities are accomplished. It examines this issue at multiple units of analysis, linking a) neurochemistry of the brain, to b) activation of specific brin regions, to c) behavioral performance on tasks requiring selection to d) self-report of the ability to select amongst alternatives in daily life. This proposal brings together a multi-disciplinary team of scientists that articulated and tested the original model in adults (cognitive and developmental neuroscientists, and a physicist with expertise in brain imaging) with a clinical scientist with expertise in development of anxiety and depression during adolescence. The project leverages a highly retained sample of youth and their caregivers who have been prospectively followed for 5 years with extensive evaluation of psychopathology, but have not previously undergone neuroimaging or evaluation of planning or control. The project will test 144 youth (72 middle and 72 older adolescents) and 72 adults both at an initial time point and then two years later. This project aims to determine the development of biobehavioral mechanisms for selection in adolescence and adulthood (Aim 1), associations between selection mechanisms and anxiety and depression (Aim 2), and how these selection mechanisms over time may predict changes in psychopathology and/or vice versa (Aim 3). The proposed research will make a significant, innovative impact by providing information about important processes that develop during adolescence, and their relationship to the onset of mental illness. The data provided by the project will help break new ground and advance the field's understanding of developmental changes in the interplay of control and planning with mental health during the critical adolescent period.