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

项目摘要/摘要 拟议的研究和培训计划旨在促进我作为一个独立的 邻居特征领域的调查员，因为它们与通过 临床精神病高危青年(CHR-P)的神经生物学和心理社会介体。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 治疗精神分裂症。最近的研究表明，社会压力可能解释了这种联系。在……里面 特别是，邻里居住不稳定(NRI)被用来衡量社会碎片化，并 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预测首发精神病患者的发病年龄更早，即使在 控制已知的风险因素。此外，我的初步数据显示，县级住宅 儿童时期的不稳定(NRI的粗略指标)1)预测转化为精神病，2)预测较小 皮质缘灰质体积(GMV)在CHR-P不动的一组青年中的变化。沃克博士(一名 我的导师)表明，以童年同龄人减少来衡量的心理社会剥夺 关系、父母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)则不是。基于 这些发现，我假设NRI导致心理社会剥夺，这反过来又有助于更小 皮质边缘GMV，最终会增加患精神病的风险。为了检验这一假设，我提出了 以下具体目标：(1)测试NRI与转化为精神病和皮质边缘障碍之间的关联 GMV，包括皮质、生殖器前扣带回皮质，以及海马GMV和控制区 包括脑岛和丘脑。(2)测试NRI与心理社会剥夺和威胁之间的关系。 (3)探索青年在不同于NRI的居民区生活的经历和情况， 从非常不稳定到高度稳定。拟议的研究将提供一种新的整合多个层面的 调查，包括公共卫生、人类发育研究和环境影响 影响大脑和行为的因素，以发现新的干预目标 社区水平，以防止或减轻高危个体的精神病转化。未来的研究将 进一步阐明邻里关系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在特定地点暴露于 发育期和大脑局部变化会对精神病产生不同的影响。如果NRI领先 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 然后可以为处于危险中的青少年设计。此外，高危人群的地理识别可以指导 将精神卫生资源分配到精神病风险较高的地区进行早期干预。

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.