Neural Nature of Persecutory Ideation in Schizophrenia

描述（由申请人提供）：被害意念发生在多种神经精神疾病中；它可能对治疗产生抗药性，并与突出的负面影响以及暴力行为风险增加有关。生物学基础目前尚不清楚，尽管两个主要系统已被提出作为潜在的神经生物学：额纹状体区域和单独的颞顶叶区域。最近的脑功能理论表明，复杂的行为可能不是孤立的区域或系统，而是由不同大脑区域之间的局部和全局连接的组合来更好地代表。因此，对大规模神经连接如何与妄想相关联的彻底检查是有必要的，以增加对病因的理解。利用明尼苏达信任游戏（囚徒困境游戏的一种新变体），该项目将采用功能连接方法来评估网络内和网络间连接对涉及猜疑的神经结构的贡献。分析将针对与理论的额纹状体和颞顶叶区域相关的连通性指标

DESCRIPTION (provided by applicant): Persecutory ideation occurs across multiple neuropsychiatric disorders; it can be resistant to treatment, and is associated with prominent negative affect as well as an increased risk of violent acts. The biological substrates currently remain unclear although two main systems have been proposed as the underlying neurobiology: frontal-striatal regions, and separately, temporo-parietal regions. Recent theories of brain functioning suggest rather than isolated regions or systems, complex behaviors may be better represented by a combination of local and global connections between distinct brain regions. Therefore, a thorough examination of how large- scale neural connectivity is associated with delusional ideation is warranted to increase understanding of the etiology. Using the Minnesota Trust Game, a novel variant of the Prisoner's Dilemma Game, the project will employ a functional connectivity approach to assess both the intra- and inter-network connectivity contributions to the neural architecture involved in suspiciousness. Analyses will target connectivity metrics associated with the theorized frontal-striatal and temporo-parietal regions to evaluate the degree to which these systems are engaged during the task, and the capacity for derived metrics to predict individual differences in persecutory ideation. The first primary goal i to develop a theory driven biomarker of suspiciousness by investigating functional magnetic resonance data from a sample of schizophrenia patients and a sample of community dwelling monozygotic twins who played the Minnesota Trust Game while in the scanner. This includes assessment of the external validation of the biomarker by examining associations with individual differences in persecutory ideation, or alienation which is an approximation of psychosis-like experiences in community participants. It also includes investigating whether discordance in connectivity metrics predicts discordance in personality traits in twins. The second primary goal is to test generalizability of the biomarker by evaluating the capacity of corresponding connectivity metrics, derived from resting-state, to predict similar relationships with individual differences in persecutory ideation in a separate sample of schizophrenia patients and controls. Follow-up analyses will evaluate the specificity of these associations. Furthermore, the capacity of the networks to distinguish patients from controls, and moreover, first-episode from chronic patients will also be investigated. Through this work procedures may identify connectivity hubs which appear to be critical for the experience of persecutory ideation, and thus could be employed as targets for future treatments and biomarkers to identify those at risk for these distressing beliefs.