The Impact of Stress and Trauma on White Matter Integrity and Psychotic-like Experiences

项目摘要/摘要 患有精神分裂症和相关障碍的人会经历与精神病相关的巨大痛苦 症状、认知缺陷和功能结果差，这代表着巨大的个人和公共健康 负担。在整个精神病谱系中都发现了白质(WM)异常：来自那些患有 精神分裂症到有精神病样经历的非求助个人(PLE；亚临床，减弱 阳性精神病症状的版本)。WM功能障碍也与脑功能缺陷有关 精神病谱系障碍患者的神经认知、社会认知和功能结果。 因此，在精神病发作之前确定WM功能障碍的贡献者对于早期诊断至关重要 识别和预防转化为更严重形式的精神疾病。最近的研究发现 精神分裂症患者延长的应激反应与WM完整性之间的关系 创伤后应激动物和个体早期生活创伤与工作记忆完整性的相关性 精神障碍；然而，WM功能障碍的心理社会相关因素尚未在个体中确定 体验PLES。建议的研究将利用弥散加权成像(DWI)在非求助 对16-24岁经历一系列PLE的社区样本进行调查 心理社会应激和创伤性生活事件对WM异常与PLES关系的影响 检查性别和PLE亚型对这些关系的贡献。这项研究代表了一项重要的 在有精神病谱系的个体中确定WM功能障碍的原因机制 疾病，以及描述干预措施的重要目标。这笔奖学金将使我能够获得 额外的培训机会，特别是在神经成像分析方面，这超出了我的范围 如果没有我自己的资金来源，我就没有时间接受。我和我的赞助商 我设计了一个培训计划，使我能够学习神经成像分析，获得更多关于 精神病的领域和压力的一般影响，学习统计处理方法需要我的 论文项目，并获得必要的技能，为我未来的职业生涯作为一名独立的调查员。这个 对此奖学金的支持将使我能够完善我的教育，并发展成为一名富有成效和影响力的 研究人员，确定精神病谱系障碍的因果机制。

Project Summary/Abstract Individuals with schizophrenia and related disorders experience significant distress related to psychotic symptoms, cognitive deficits, and poor functional outcomes, which represent a large personal and public health burden. White matter (WM) abnormalities have been found across the psychosis spectrum: from those with schizophrenia to non-help-seeking individuals with psychotic-like experiences (PLEs; subclinical, attenuated version of positive psychotic symptoms). WM dysfunction has also been associated with deficits in neurocognition, social cognition, and functional outcome within individuals with psychosis spectrum disorders. As such, identifying contributors to WM dysfunction prior to the onset of psychosis is crucial for early identification and preventing conversion to more severe forms of psychotic illness. Recent studies have found associations between prolonged stress response and WM integrity in individuals with schizophrenia, as well as correlations between early life trauma and WM integrity in animals and individuals with post-traumatic stress disorder; however, psychosocial correlates of WM dysfunction have not yet been identified in individuals experiencing PLEs. The proposed study will utilize diffusion weighted imaging (DWI) within a non-help-seeking community sample of 16 – 24 year olds experiencing a range of PLEs to examine the contribution of psychosocial stress and traumatic life events to the relationship between WM abnormalities and PLEs, and examine the contribution of sex and subtype of PLE to these relationships. This study represents an important step toward identifying causal mechanisms for WM dysfunction within individuals with psychosis spectrum disorders, as well as delineating important targets for interventions. This fellowship would allow me to obtain additional training opportunities, particularly in neuroimaging analysis, which are beyond the scope of my program and I would not otherwise have the time to receive without my own line of funding. My sponsors and I have designed a training plan that will allow me to learn neuroimaging analysis, gain additional expertise in the realms of psychosis and the general effects of stress, learn statistical processing methods needed for my dissertation project, and gain the skills necessary for my future career as an independent investigator. The support of this fellowship will allow me to round out my education and develop into a productive and impactful researcher, identifying causal mechanisms for psychosis spectrum disorders.