Impact of Neighborhood Characteristics on Conversion to Psychosis among Youth at Clinical High Risk for Psychosis

项目总结/摘要 建议的研究和培训计划旨在促进我作为一个独立的发展 调查员在该领域的邻里特点，因为他们涉及到转换为精神病，通过 精神病临床高危青年中的神经生物学和心理社会介质（CHR-P）。城市 教养（与农村地区相比，在城市长大）是最大的环境风险因素之一 精神分裂症最近的研究表明，社会压力可以解释这种联系。在 特别是，邻里住宅不稳定性（NRI）已被用来衡量社会分裂， 也与精神分裂症发病率和患病率的增加有关。此外，我发表的作品发现， NRI预测，即使在第一次精神病发作后， 控制已知的风险因素。此外，我的初步数据表明，县级住宅 儿童期的不稳定性（NRI的粗略代表）1）预测转化为精神病，2）预测较小的 皮质边缘灰质体积（GMV）在CHR-P的一个子集的青年谁从来没有移动。步行者博士（一名 我的导师）已经表明，心理社会剥夺， 关系，父母的缺席和情感忽视与较小的皮质边缘GMV相关，而 威胁（定义为涉及伤害的暴露;例如，儿童期性虐待和身体虐待）。基于 这些发现，我假设NRI导致心理社会剥夺，这反过来又有助于较小的 皮质边缘GMV，最终增加精神病的风险。为了验证这一假设，我提出了 以下具体目的：（1）测试NRI与精神病转化和皮质边缘系统的关系。 GMV，包括皮质、膝周前扣带回皮质和海马GMV和对照区 包括丘脑和丘脑。(2)测试NRI与心理社会剥夺和威胁之间的关联。 (3)探索居住在NRI不同居民区的CHR-P青年的经历和情况， 从非常不稳定到高度稳定。拟议的研究将提供一种新的多层次的整合， 调查，包括公共卫生，人类发育研究，以及环境影响 大脑和行为的因素，以发现新的干预目标，无论是在个人和 社区水平，以防止或减轻高风险个体的精神病转化。未来的研究将 进一步阐明邻里特征与心理社会和神经生物学的关系 与精神病风险相关的因素，例如调查NRI暴露是否在特定的 发育时期和大脑区域变化对精神病有不同的影响。如果NRI领导 心理社会剥夺和神经生物学变化，例如，有针对性的心理社会干预 可以为处于危险中的青少年设计。此外，对风险群体的地理识别可以指导 向精神病风险较高的地区分配精神卫生资源，以便及早干预。

Project Summary/Abstract The proposed research and training plan are designed to promote my development as an independent investigator in the field of neighborhood characteristics as they relate to conversion to psychosis through neurobiological and psychosocial mediators among youth at clinical high risk for psychosis (CHR-P). Urban upbringing (growing up in cities as compared to rural areas) is one of the strongest environmental risk factors for schizophrenia. More recent studies have suggested that social stress might explain this association. In particular, neighborhood residential instability (NRI) has been used to measure social fragmentation and has also been associated with increased schizophrenia rates and prevalence. In addition, my published work found that NRI predicts an earlier age at onset of psychosis among individuals with first-episode psychosis even after controlling for known risk factors. Furthermore, my preliminary data indicate that county-level residential instability (a rough proxy for NRI) during childhood 1) predicts conversion to psychosis and 2) predicts smaller corticolimbic gray matter volume (GMV) among a subset of youth at CHR-P who never moved. Dr. Walker (one of my mentors) has shown that psychosocial deprivation as measured by reduced childhood peer relationships, parental absence, and emotional neglect is associated with smaller corticolimbic GMV, whereas threat (defined as exposures that involve harm; e.g., childhood sexual and physical abuse) is not. Based on these findings, I hypothesize that NRI leads to psychosocial deprivation, which in turn contributes to smaller corticolimbic GMV, which ultimately increases risk for psychosis. To test this hypothesis, I propose the following Specific Aims: (1) Test the association between NRI and conversion to psychosis and corticolimbic GMV, including the cortical, perigenual anterior cingulate cortex, and hippocampal GMV and control regions including insula and thalamus. (2) Test the association between NRI and psychosocial deprivation and threat. (3) Explore the experiences and circumstances of youth at CHR-P living in residential areas that differ in NRI, from very unstable to highly stable. The proposed studies will provide a novel integration of multiple levels of investigation including public health, developmental studies in humans, and the impact of environmental factors on the brain and behavior to discover novel targets for intervention both at the individual and neighborhood levels to prevent or mitigate psychosis conversion in high-risk individuals. Future research will further elucidate the relationship of neighborhood characteristics with the psychosocial and neurobiological factors associated with risk for psychosis, such as investigating whether NRI exposure at specific developmental periods and regional brain changes would have a differential impact on psychosis. If NRI leads to psychosocial deprivation and neurobiological changes, for example, targeted psychosocial interventions could then be designed for youth at risk. In addition, geographic identification of at-risk groups could guide allocation of mental health resources to areas with greater psychosis risk for early intervention.