Exploring Neurological & Endocrine Determinants of Risk Behavior Decision-Making

描述（由申请人提供）：作为对项目公告（PA-09-040）的回应，这份名为“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”的K01提案提出了一种严格的混合方法来研究青少年和年轻人（18-24岁）如何做出参与危险行为的决定。这项为期一年的纵向研究是同类研究中的第一个，它将功能磁共振成像、唾液样本、生殖器棉签、ACASI（音频计算机辅助自我访谈）和即时短信调查方法整合到一个项目中，以检查性风险行为和物质使用及其相关结果（例如，艾滋病毒、性传播感染、物质使用障碍、药物依赖、抑郁）的神经、激素、心理和环境决定因素。本研究的目的和具体目的如下：目的：推动本研究的研究问题是：当年轻人知道后果时，为什么他们会从事危险行为（性行为和物质使用）？这些青年在多大程度上经历抑郁症状、压力加剧和身体后果（例如性传播感染、艾滋病毒、药物使用障碍）？风险和结果的决定因素之间的关系如何随时间变化？目的1：利用功能磁共振成像评估认知是否控制感兴趣的大脑区域(CCROIs：前额叶皮层修剪和顶叶关联皮层、背外侧前额叶皮层、腹内侧前额叶皮层；前扣带和后扣带，以及颞顶叶皮质)和社会情感感兴趣的大脑区域（SEROIs：内侧额叶皮质，左侧腹侧纹状体-伏隔，左侧颞上沟，左侧内侧颞叶，杏仁核）在性和物质使用风险较小的年轻人中与风险较大的年轻人相比，活跃程度有所不同。目的2：通过每天四次唾液测量，评估年轻女性和男性的睾酮(T)和脱氢表雄酮（DHEA）水平和每日模式是否随认知控制和社会情感网络大脑区域活动和发展的功能而变化。目的3：调查与社会经济大脑网络相关的认知控制激活如何与青少年报告的(a)心理健康结果和(b)身体健康结果相关。进一步，评估激素和大脑区域模式（例如，高T与低认知控制）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之间的关系。目的4：评估在一年的发育过程中大脑功能的变化以及激素的昼夜变化，以及这些变化是否(1)彼此相关，(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。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，足以让我开始独立的职业生涯；(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风险行为，以及这些激素和大脑ROI如何随着时间的推移与风险行为和心理健康结果相关。这项工作将通过整合心理学、生物学和环境视角，创建和评估一个更全面的模型，从而提高青少年和年轻人决策、心理健康和行为结果的现有知识，并将作为R01应用和本研究范围之外的未来分析的基础。

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.