Neural Nature of Persecutory Ideation in Schizophrenia

描述(由申请人提供)：迫害意念发生在多种神经精神障碍中；它可以抵抗治疗，并与突出的负面影响以及暴力行为的风险增加有关。尽管已经提出了两个主要的神经生物学系统：额叶-纹状体区域和单独的颞顶区域，但目前生物底物仍不清楚。最近的大脑功能理论表明，复杂的行为可能更好地表现为不同大脑区域之间的局部和全局联系的组合，而不是孤立的区域或系统。因此，彻底检查大规模神经连接与妄想症的关联是有必要的，以增加对病因的理解。使用明尼苏达信任游戏，囚犯困境游戏的一个新变体，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怀疑的神经架构的贡献。分析将针对与理论化的额叶-纹状体和颞顶区相关的连通性指标 评估这些系统在任务中的参与程度，以及衍生指标预测迫害意念中个体差异的能力。第一个主要目标是通过研究精神分裂症患者样本和社区居住的同卵双胞胎样本的功能磁共振数据，开发一个理论驱动的可疑生物标记物。他们在扫描仪上玩明尼苏达信任游戏。这包括评估生物标志物的外部有效性，方法是检查受迫害意念的个体差异与社区参与者的疏离感或疏离感的关系，疏离感是社区参与者类似精神病的经历的近似值。它还包括调查连通性指标的不一致是否预示着双胞胎的人格特征不一致。第二个主要目标是通过评估来自静息状态的相应连接性指标的能力来测试该生物标记物的普适性，以预测与精神分裂症患者和对照组的单独样本中迫害意念的个体差异的类似关系。后续分析将评估这些关联的特异性。此外，还将调查网络区分患者和对照组的能力，以及区分首发患者和慢性病患者的能力。通过这一工作程序，可以确定似乎对遭受迫害的意念体验至关重要的连接枢纽，从而可以用作未来治疗的目标和生物标记物，以确定那些面临这些令人痛苦的信念风险的人。

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.