Development Trajectories of Negative Symptoms in Schizophrenia

精神分裂症阴性症状的发展轨迹

• 批准号: 8887151
• 负责人: Raquel E Gur
• 金额: $ 15.84万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-08 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8887151
• 关键词: 3-Dimensional; Adolescence; Adolescent and Young Adult; Affect; Amygdaloid structure; Anatomy; Anxiety; Brain; Clinical; Complement; Data; Development; Early identification; Electroencephalography; Electrophysiology (science); Emotional; Equilibrium; Exhibits; Extinction (Psychology); Fright; Functional Magnetic Resonance Imaging; Functional disorder; Genomics; Goals; Individual; Insula of Reil; Knowledge; Lateral; Learning; Measures; Mediating; Methods; Molecular; National Institute of Mental Health; Participant; Patients; Peripheral; Phenotype; Physiological; Prefrontal Cortex; Procedures; Process; Psychotic Disorders; Relative (related person); Research Domain Criteria; Resolution; Rest; Reversal Learning; Risk; Rodent; Role; Sampling; Schizophrenia; Social Functioning; Social Values; Stimulus; Strategic Planning; Symptoms; Testing; Time; Ventral Striatum; Youth; aversive conditioning; blood oxygenation level dependent response; clinical phenotype; clinical risk; emerging adult; functional disability; indexing; network dysfunction; neurobehavioral; neuroimaging; neurophysiology; relating to nervous system; research study; response; social

Negative symptoms in schizophrenia present a challenge to treatment and are associated with profound functional impairment. Characterizing the developmental trajectory of these symptoms and their relation to the emergence of schizophrenia and psychosis during adolescence and early adulthood is an essential prerequisite for early identification and clinical intervenfion. The overall goal of this Project is to probe brain circuitry that underlies the core domain of negative symptoms of diminished emotional expressivity and social drive, in informative youths at risk for psychosis and early in the course of illness. By applying deep phenotyping of clinical, neurobehavioral, physiologic and anatomic measures that complement the rodent studies (Projects II, 111) and can be integrated with cellular, molecular and genomic data (Projects IV, V), we hope to propel the field and elucidate key features of schizophrenia that require better understanding leading to new treatments. Project I will specifically contribute to elucidafing how neural responses are modulated by aversive conditioning and extinction and how these processes are impaired in affected and at risk youths. Complementary EEG and fMRI methods will help test the hypothesis that dysregulation of amgydala and its role in circuits mediating negative emofion processing contribute to schizophrenia risk, negative symptoms, and social dysfunction. The sample will include 225 youths characterized in Core A. There will be 75 participants in each group of patients with schizophrenia, clinical risk and healthy controls. They will each undergo an fMRI and an EEG experiment in a counter-balanced order. Complementary tasks that probe amygdala circuitry will be administered in the studies. The EEG procedure will include more refined gradation of timing parameters and the fMRI will provide 3-D anatomical resolution and amygdala integrity and activation measures. Basal and activation parameteres will be related to dimensional measures of negative symptomatology, social function and social learning of positive and negative value.

精神分裂症的负面症状对治疗提出了挑战，与深刻有关 功能障碍。表征这些症状的发育轨迹及其与之的关系 青春期和成年早期的精神分裂症和精神病的出现是必不可少的 早期识别和临床干预的先决条件。该项目的总体目标是探测大脑 电路是降低情绪表达和降低的负面症状的核心领域 社交动力，在有信息的年轻人中有精神病风险和疾病早期。通过深处 临床，神经行为，生理和解剖学测量的表型，以补充啮齿动物 研究（项目II，111），可以与细胞，分子和基因组数据（项目IV，V）集成，我们 希望推动该领域并阐明精神分裂症的关键特征，这些特征需要更好地理解领导 进行新的治疗。项目我将专门为Elucidafe做出贡献 厌恶调理和灭绝以及这些过程如何受到影响和处于风险的年轻人的损害。 互补的脑电图和fMRI方法将有助于测试Amgydala及其失调的假设 在介导负Emofion加工的电路中的作用有助于精神分裂症的风险，负症状， 和社会功能障碍。 样本将包括225名以核心为特征的年轻人。每组将有75名参与者 精神分裂症，临床风险和健康对照的患者。他们每个人都会接受fMRI和脑电图 实验以平衡顺序。探测杏仁核电路的互补任务 在研究中进行管理。脑电图程序将包括更多的定时参数等级，并且 fMRI将提供3D解剖分辨率和杏仁核的完整性和激活措施。基础和 激活参数将与负面症状，社会功能的维度测量有关 以及积极和负值的社会学习。