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.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这个项目将检验精神分裂症患者特定的皮质-纹状体回路功能障碍的假设。虽然在少数有关精神分裂症患者的研究中有证据表明纹状体功能障碍，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病药物的效果不可避免地混为一谈。该项目将通过研究两组易患精神分裂症的青少年(有精神分裂症前驱症状的患者和儿童时期起病的患者的兄弟姐妹)来避免这一陷阱，但他们不是精神病患者，因此没有接受抗精神病药物治疗。先前的研究，包括我们的研究表明，精神分裂症患者的认知DLPFC/尾状核和“奖励”前扣带/腹侧纹状体和LOF/腹尾状回回路受损，而运动皮质/壳核回路完好无损。技能学习任务和功能磁共振成像的组合将被用来检验这一假设。在拨款的第一年，我们将开发一个奖赏处理任务，分别评估奖赏大小和奖赏可预测性对fMRI激活的影响，并开发具有类似心理测量学特性的认知习惯和运动技能学习任务。在拨款的第二年和第三年，我们将对20名儿童首发精神分裂症患者的兄弟姐妹、40名有精神分裂症前驱症状的患者和20名青少年对照组进行大规模的初步研究。我们将测试这一假设，即不同皮质-纹状体功能障碍的技能学习表现和功能磁共振指数将与精神分裂症易感性个体的独特临床特征、神经心理缺陷和功能结果相关，这取决于受影响的假定回路。这是第一项精神分裂症研究：1)使用心理测量匹配任务和fMRI激活的证据的融合来测试有关特定纹状体回路损伤的假说，2)分别评估奖励幅度和可预测性对大脑活动的影响，3)通过研究从未患过精神病、因此没有接受抗精神病药物治疗的易患精神分裂症的青少年，证明特定的皮质-纹状体损伤不是由于抗精神病药物的影响。