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在新的艾滋病毒/性传播感染(STI)中占越来越多的比例，而预防工作严重滞后。我们的主要假设是，在某些人中，标准艾滋病毒干预的有效性可能会因为大脑在做出最佳的“一时冲动”风险决策的能力上的差异而受到破坏。在正常发育中，青春期对奖励敏感、受冲动驱动的大脑逐渐变成成年人的大脑，对奖励冲动的抑制程度有所改善。然而，这种大脑的成熟具有很大的个体差异性--而发育延迟(暂时或持续)可能会导致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(反映在一系列危险行为上-包括第一次性行为的早期、频繁的无保护性行为、多个性伴侣、多发性传播疾病)，使一群年轻女性处于艾滋病毒的高性风险(HSR)。具有这种HSR表型的年轻女性是否真的有一种“更年轻”的大脑行为脆弱性模式(BBV是与奖励相关的大脑过程，可能会破坏最佳决策)？一项组间设计(HSR与低性风险，LSR)将从城市计划生育中招募18-24岁的女性，该城市的艾滋病毒感染率是全国的5倍，黑人占新增艾滋病毒病例的66%。这项研究将使用选定的fMRI探针和行为任务，在4个领域比较HSR v LSR组与HIV风险相关的BBV(奖励敏感度高、冒险程度高、奖赏冲动抑制程度低、拒绝敏感度高)。我们开创性的“概念验证”R21研究的具体目的是确定患有高铁的年轻城市女性是否比那些患有LSR的年轻女性有更大的BBV。为了做到这一点，我们将：A)比较HSR和LSR患者大脑中先验区域的激活情况，以及B)将在扫描仪上任务中获得的大脑激活模式与关联的(非扫描仪)行为得分相关联。我们假设，那些患有HSR的人将在与艾滋病毒风险相关的一个或多个领域中表现出明显更大的脆弱性(先验区域的更大反应)，并且行为得分将与指定的先前感兴趣区域的大脑活动显著相关，直接将大脑活动与风险相关行为联系起来。我们的探索目的是通过调查评估来描述高铁和低铁人群的人口统计、健康和艾滋病毒危险行为的特征，为检验其他潜在的关联(童年创伤、伴侣暴力、抑郁症、认知能力)提供一个假说生成的数据基础。 与艾滋病毒风险相关的大脑数据。在HSR v.LSR中展示年轻女性在艾滋病毒方面的BBV差异，并确定潜在的大脑过程将使我们能够实现长期目标：鼓励对艾滋病毒风险有更广泛的生物学基础的理解，并为脆弱个人开辟新的大脑定向和/或大脑知情战略，从而获得挽救生命的好处。

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.