Do brain differences influence HIV risk behavior? A study of young urban women

描述（由申请人提供）：年轻的城市少数民族妇女占越来越多的新的艾滋病毒/性传播感染（STI），而预防工作严重滞后。我们的首要假设是，标准的艾滋病毒干预措施的有效性可能会受到某些人的大脑差异的能力，使最佳的“在最热的时刻”的风险决策。在正常的发育过程中，青少年时期对奖励敏感、冲动驱动的大脑逐渐变成了成年人的大脑，对奖励冲动的抑制能力得到了改善。然而，这种大脑成熟有很大的个体差异性，发育延迟（暂时的或持续的）可能会导致一个成年人具有“青少年”大脑的决策特征。 基于我们的试点数据集（n=142），我们假设发育迟缓可能导致次优性决策（反映在一组风险行为中-包括过早的第一次性行为，频繁的无保护性行为，多个性伴侣，多种性传播感染），使一个年轻女性亚组处于艾滋病毒的高性风险（HSR）。具有这种HSR表型的年轻女性真的具有“年轻”大脑行为脆弱性的模式吗（BBV是与奖励相关的大脑过程，可以破坏最佳决策）？组间设计（HSR与低性风险，LSR）将招募来自城市计划生育的18-24岁女性，该城市的艾滋病毒感染率是全国的5倍，黑人占新发艾滋病毒病例的66%。该研究将使用选定的功能磁共振成像探针和行为任务，在4个与艾滋病毒风险相关的领域（奖励敏感性提高，更大的风险承担和对奖励冲动的不良抑制，以及更大的拒绝敏感性）中比较HSR v LSR组的BBV。我们开创性的“概念验证”R21研究的具体目标是确定与LSR相比，HSR的年轻城市女性是否具有更大的BBV。为此，我们将：A）比较HSR与LSR患者大脑先验区域的激活情况，以及~ B）将扫描仪上任务中获得的大脑激活模式与相关（扫描仪外）行为评分相关联。我们假设，HSR患者在与HIV风险相关的一个或多个领域中表现出更大的脆弱性（先验区域的反应更大），并且行为评分将与特定先验区域的大脑活动显着相关，直接将大脑活动与风险相关行为联系起来。我们的探索性目的是通过调查评估来描述HSR和LSR群体的人口统计学，健康和HIV风险行为，为研究其他潜在的关联（童年创伤，伴侣暴力，抑郁症，认知能力）提供一个假设生成数据库。 HIV风险相关的大脑数据。在HSR v. LSR中证明年轻女性BBV的差异，并确定潜在的大脑过程将使我们的长期目标成为可能：鼓励对艾滋病毒风险进行更广泛的基于生物学的理解，并为弱势个体开辟新的大脑靶向和/或大脑知情策略的道路，具有拯救生命的益处。

DESCRIPTION (provided by applicant): Young, urban minority women account for a growing number of new HIV/sexually transmitted infections (STIs), while prevention efforts are seriously lagging behind. Our overarching hypothesis is that efficacy of standard HIV interventions may be undermined in certain individuals by brain differences in the ability to make optimal "in the heat of the moment" risk decisions. In normal development, the reward-sensitive, impulse-driven brain of adolescence gradually becomes an adult brain with improved inhibition of reward impulses. This brain maturation, however, has a great deal of individual variability - and developmental delay (temporary or sustained) can result in a chronological adult with decision-making characteristics of an 'adolescent' brain. Based on our pilot dataset (n=142), we hypothesize that developmental delay may contribute to sub-optimal sexual decision-making (reflected in a cluster of risk behaviors - including early age of 1st sex, frequent unprotected sex, multiple sexual partners, multiple STIs) putting a subgroup of young women, at high sexual risk (HSR) for HIV. Do young women with this HSR phenotype indeed have a pattern of "younger" brain- behavioral vulnerabilities (BBVs are reward-relevant brain processes that can undermine optimal decision- making)? A between-groups design (HSR vs. low sexual risk, LSR) will recruit 18-24 year-old females from an urban family planning in a city with 5 times the national HIV rate with blacks accounting for 66% of new HIV cases. The study will compare BBVs for the HSR v LSR group in 4 domains with HIV risk-relevance (heightened reward sensitivity, greater risk taking and poor inhibition of reward impulses, and greater rejection sensitivity), using selected fMRI probes and behavioral tasks. The specific aim of our pioneering "proof-of- concept" R21 study is to determine whether young urban women with HSR have greater BBVs compared to those that have LSR. To accomplish this we will: A) Compare activation in a priori regions of the brain between those with HSR vs. LSR and~ B) Correlate brain activation patterns obtained in the on-scanner tasks with linked (off-scanner) behavioral scores. We hypothesize that those with HSR will evidence significantly greater vulnerability (greater response in a priori regions) in one or more domains relevant for HIV risk, and that behavioral scores will be significantly correlated with the brain activity in the specified a prior regions of interest, directly linking brain activity with the risk-relevant behavior. Our exploratoy aim is to characterize demographic, health and HIV risk behaviors of the HSR and LSR groups through survey assessment, providing an hypothesis-generating data-base for examining other potential associations (childhood trauma, partner violence, depression, cognitive ability) with our HIV risk-relevant brain data. Demonstrating a difference in BBVs for young women at HSR v. LSR for HIV and identifying the underlying brain processes would enable our long-term goals: to encourage a broader biologically-based understanding of HIV risk, and to open the way for new brain-targeted and/or brain-informed strategies for vulnerable individuals, with life-saving benefit.