Exploring Neurological & Endocrine Determinants of Risk Behavior Decision-Making

描述（由申请人提供）：本K 01提案题为“走向独立：探索青少年和年轻人风险行为决策的神经和内分泌决定因素”，以响应计划公告（PA-09-040），提出了一种严格的混合方法方法，以检查青少年和年轻人（18-24岁）如何做出参与风险行为的决定。这项为期一年的纵向研究是同类研究中的第一项，将fMRI，唾液样本，生殖器拭子和ACASI（音频计算机辅助自我采访）和即时短信调查方法纳入一个项目，以检查性风险实践和药物使用及其相关结果的神经，激素，心理和背景决定因素（例如，艾滋病毒、性传播感染、物质使用障碍、药物依赖、抑郁症）。本研究的目的和具体目标如下：目的：激励拟议的研究的研究问题是：为什么年轻人从事危险行为（性和物质使用）时，他们知道的后果？这些年轻人在多大程度上经历了抑郁症状、高度压力和身体后果（例如，性传播感染、艾滋病毒、吸毒障碍）？风险和结果的决定因素之间的关系如何随时间变化？目标1：使用功能磁共振成像评估是否认知控制感兴趣的大脑区域（CROI：前额叶皮层修剪和顶叶联合皮层;背外侧前额叶皮层;腹内侧前额叶皮层;前扣带回和后扣带回，以及颞顶叶皮层）和社会情感大脑区域的兴趣（血清：内侧额叶皮质，左侧腹侧纹状体-在小脑，左侧上级颞沟，左侧内侧颞，杏仁核）在性行为和药物使用风险较低的青年与风险较高的青年中的活跃程度不同。目标二：通过每天四次唾液测量，评估睾酮（T）和脱氢表雄酮（DHEA）水平和昼夜模式是否随年轻女性和男性的认知控制和社会情感网络脑区活动和发育而变化。目标3：调查认知控制相对于社会经济大脑网络的激活如何与青少年的报告（a）心理健康结果和（B）身体健康结果相关。通过扩展，评估激素和大脑区域模式（例如，高T低认知控制）与青少年报告的性风险、物质使用、药物滥用和依赖以及心理健康有关。目标4：评估大脑功能的变化，以及激素昼夜变化超过一年的发展，以及这些变化是否与（1）彼此和（2）性风险行为和物质使用结果以及心理健康结果的变化/稳定性相关。在这个项目完成后，作为一名年轻的研究者，我将（1）学习神经科学和内分泌学的基础知识，足以开始我的独立职业生涯，（2）更好地了解激素，大脑区域活动和环境如何影响年轻人的危险行为，以及这些激素和大脑ROI如何与危险行为和心理健康结果相关。这项工作将通过整合心理，生物和背景视角创建和评估一个更全面的模型来推进青少年和年轻人决策以及心理健康和行为结果的现有知识，并将作为R 01应用和未来分析的基础超出本研究的范围。 公共卫生相关性：走向独立：探索青少年和年轻人危险行为决策的神经和内分泌决定因素项目叙述候选人的直接培训和研究议程是发展一个更好的和全面的理解-使用生物和调查措施-青少年和年轻人如何做出决定从事危险行为。拟议的为期1年的纵向研究重点是了解危险的性行为和物质使用决策和相关结果（例如，艾滋病毒，性传播感染，物质使用障碍，药物依赖，抑郁症）从神经科学和内分泌学的角度，在候选人寻求培训的学科。这一研究议程对青少年和青年人的福祉具有重大的政策和预防影响。

DESCRIPTION (provided by applicant): This K01 proposal entitled "Moving Toward Independence: Exploring neurological and endocrine determinants of adolescent and young adult risky behavior decision-making" in response to the program announcement (PA-09-040) proposes a rigorous mixed methods approach to examine how adolescents and young adults (ages 18-24) make decisions about engaging in risky behaviors. This one-year longitudinal study, the first of its kind, incorporates fMRI, salivary samples, genital swabs, and ACASI (Audio Computer Assisted Self-Interview) and in-the-moment text messaging survey methods into one project to examine neurological, hormonal, psychological, and contextual determinants of sexual risk practices and substance use and their related outcomes (e.g., HIV, STIs, substance use disorders, drug dependency, depression). The objective and specific aims of this study are listed below: Objective: The research questions motivating the proposed study are: Why do young adults engage in risky behaviors (sexual and substance use) when they are knowledgeable about consequences? To what extent do these youth experience feelings of depressive symptoms, heightened stress, and physical consequences (e.g., STIs, HIV, drug use disorders)? How do relationships between determinants of risk and outcomes change over time? Aim 1: Assess, using fMRI whether cognitive control brain regions of interest (CCROIs: prefrontal cortex pruning and parietal association cortex; dorsolateral prefrontal cortex; ventromedial prefrontal cortex; anterior and posterior cingulate, and temporo-parietal cortices) and socio-emotional brain regions of interest (SEROIs: medial frontal cortex, left ventral striatum - in the accumbens, left superior temporal sulcus, left medial tempor- al, amygdala) are differentially active in youths who take fewer sexual and substance use risks relative to youths taking greater risks. Aim 2: Assess, via four salivary measures per day, whether testosterone (T) and dehydroepiandrosterone (DHEA) levels and diurnal patterns vary as a function of the cognitive control and socio-emotional network brain region activity and development for young women and men. Aim 3: Investigate how activation in cognitive control relative to socio-economic brain networks relates to youths' reports of (a) mental health outcomes and (b) physical health outcomes. By extension, assess how hormone and brain region patterns (e.g., high T with low cognitive control) relate to youths' reports of sexual risk, substance use, drug abuse and dependency, and mental health. Aim 4: Assess changes in brain function as well as hormone diurnal changes over one year's development and whether these changes are related to (1) each other and (2) changes/ stability in sexual risk behavior and substance use outcomes as well as mental health outcomes. At the completion of this project, as a young investigator I will (1) learn the fundamentals of neuroscience and endocrinology, sufficient to launch my independent career, and (2) have a better understanding of how hormones, brain region activity, and context influence a young person's risky behaviors and how these hormones and brain ROI relate to risky behaviors and mental health outcomes over time. This work will advance the current knowledge of adolescent and young adult decision-making and mental health and behavioral outcomes by creating and assessing a more comprehensive model via integrating psychological, biological, and contextual perspectives, and will serve as the basis for an R01 application and future analyses beyond the scope of this study. PUBLIC HEALTH RELEVANCE: Moving Toward Independence: Exploring neurological and endocrine determinants of adolescent and young adult risky behavior decision-making Project Narrative The candidate's immediate training and research agenda is to develop an improved and comprehensive understanding - using biological and survey measures - of how adolescents and young adults make decisions to engage in risky behaviors. The proposed 1-year longitudinal study focuses on understanding risky sexual practice and substance use decision making and related outcomes (e.g., HIV, STIs, substance use disorders, drug dependency, depression) from neuroscience and endocrinology perspectives, disciplines in which the candidate seeks training. This research agenda has major policy and prevention implications for adolescent and young adult well-being.