CORTICAL-STRIATAL DYSFUNCTION AND VULNERABILITY TO SCHIZOPHRENIA

皮质纹状体功能障碍和精神分裂症的脆弱性

• 批准号: 7955816
• 负责人: ROBERT F ASARNOW
• 金额: $ 0.68万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7955816
• 关键词: Adolescent; Affect; Anterior; Antipsychotic Agents; Brain; Childhood; Clinical; Cognitive; Computer Retrieval of Information on Scientific Projects Database; Corpus striatum structure; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Grant; Habits; Impairment; Individual; Institution; Learning; Modeling; Motor Cortex; Patients; Performance; Pharmaceutical Preparations; Pilot Projects; Property; Psychometrics; Research; Research Personnel; Resources; Rewards; Schizophrenia; Siblings; Source; Symptoms; Testing; United States National Institutes of Health; Ventral Striatum; computational anatomy; functional outcomes; indexing; motor skill learning; neuropsychological; putamen; reward processing; skills

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This project will test the hypothesis that specific cortical-striatal circuits are dysfunctional in schizophrenia. While there is evidence of striatal dysfunction in the few relevant studies of schizophrenia patients, the effect of schizophrenia on striatal functioning was inextricably confounded with the effects of the anti-psychotic medications used to treat schizophrenia. This project will avoid this pitfall by studying two groups of adolescents with liability to schizophrenia (patients with prodromal symptoms of schizophrenia and siblings of patients with childhood onset of schizophrenia), but who are not psychotic and therefore not treated with anti-psychotic medications. Prior research, including ours, suggests that the cognitive DLPFC/Caudate and the "reward" anterior cingulate/ventral striatum and LOF/ventral caudate circuits are impaired in schizophrenia, while the motor cortex/putamen circuit is intact. A combination of skill learning tasks and fMRI will be used to test this hypothesis. In the first year of the grant we will develop a reward-processing task that separately evaluates the effect of reward magnitude and reward predictability on fMRI activation and develop cognitive habit and motor skill learning tasks with comparable psychometric properties. In the second and third years of the grant we will conduct a large-scale pilot study of 20 siblings of childhood onset schizophrenia patients, 40 patients with prodromal symptoms of schizophrenia, and 20 adolescent controls. We will test the hypothesis that skill learning performance and fMRI indices of dysfunction of different cortical-striatal dysfunction will correlate with distinctive clinical features, neuropsychological deficits, and functional outcomes in individuals with liability to schizophrenia, depending on the putative circuit affected. This is the first schizophrenia study to: 1) use the convergence of evidence from psychometrically matched tasks and fMRI activation to test hypotheses about impairments of specific striatal circuits, 2) separately evaluate the effects of reward magnitude and predictability on brain activity, 3) demonstrate that specific cortical-striatal impairments are not due to the effects of anti-psychotic medication by studying adolescents with vulnerability to schizophrenia who have never been psychotic and therefore are not treated with antipsychotic medications.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 该项目将检验以下假设：精神分裂症中特定的皮质 - 纹状体回路功能失调。虽然在精神分裂症患者的少数相关研究中有纹状体功能障碍的迹象，但精神分裂症对纹状体功能的影响与用于治疗精神分裂症的抗精神药物的影响密不可分。该项目将通过研究对精神分裂症责任的两组青少年（精神分裂症的前驱症状和精神分裂症患者的兄弟姐妹的兄弟姐妹）来避免这种陷阱，但他们不精神病，因此没有使用抗精神药物治疗。先前的研究，包括我们的研究表明，精神分裂症的认知DLPFC/尾状和“奖励”前扣带回/腹侧纹状体和lof/腹侧尾状电路受损，而运动皮层/脉络膜电路是完整的。技能学习任务和fMRI的结合将用于检验这一假设。在赠款的第一年，我们将制定一项奖励处理任务，该任务分别评估奖励幅度和奖励可预测性对fMRI激活的影响，并使用可比的心理计量学特性发展认知习惯和运动技能学习任务。在赠款的第二年和第三年中，我们将对20个儿童期兄弟姐妹精神分裂症患者，40例精神分裂症患者和20种青少年对照组进行大规模的试点研究。我们将测试以下假设：不同皮质 - 纹状体功能障碍的功能障碍的技能学习绩效和功能障碍指数将与对精神分裂症责任的个体中的独特临床特征，神经心理学缺陷以及功能性结果相关，具体取决于假定的电路。这是第一项精神分裂症研究：1）使用从心理教度匹配的任务和fMRI激活中的证据收敛，以测试有关特定纹状体循环损伤的假设，2）分别评估奖励幅度和预测性对大脑活动的影响，3）通过研究特定的皮质损害，表明对及应效果的敏感性效果，对Antner的影响效应，对Attner的影响效应效果。从来没有精神病，因此没有接受抗精神病药治疗的精神分裂症。