Prefrontal Mechanisms of Selection: Disrupted in Internalizing Psychopathology?

 描述（由申请人提供）：青春期是一个重要的发育时期，其特征在于多个领域的快速变化，包括大脑前额叶皮层的成熟，计划和认知控制的增加，以及焦虑和抑郁的比率大幅增加。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。控制的一个方面尚未得到充分研究，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竞争选项中进行选择的能力。这样的选择对任何人来说都是困难的，但对于焦虑或抑郁程度较高的人来说尤其如此，导致计划和决策方面的问题。迄今为止，这些问题主要在成人中进行研究。然而，重要的是要了解这些能力是如何在青春期发展的，因为这是精神疾病的许多方面首次出现的发展时期。拟议的研究建立在一个创新的和综合的模型，如何完成这种选择能力。它在多个分析单元中考察了这个问题，将a）大脑的神经化学，B）特定脑区的激活，c）需要选择的任务的行为表现，d）自我报告的能力 在日常生活中的各种选择中做出选择。该提案汇集了一个多学科的科学家团队，该团队阐述并测试了成年人的原始模型（认知和发展神经科学家，以及具有脑成像专业知识的物理学家）与具有青春期焦虑和抑郁发展专业知识的临床科学家。该项目利用了一个高度保留的青年和他们的照顾者的样本，他们已经前瞻性地随访了5年，对精神病理学进行了广泛的评估，但以前没有进行过神经成像或计划或控制的评估。该项目将在最初的时间点和两年后对144名青少年（72名中年和72名老年青少年）和72名成年人进行测试。该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关联（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和/或反之亦然（目标3）。拟议的研究将通过提供有关青春期发展的重要过程及其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，并促进该领域对关键青少年时期控制和规划与心理健康相互作用的发展变化的理解。

 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.