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.

精神分裂症的阴性症状对治疗提出了挑战，并且与深远的影响相关。 功能障碍。描述这些症状的发展轨迹及其与 青春期和成年早期精神分裂症和精神病的出现是一个重要因素 是早期识别和临床干预的前提。该项目的总体目标是探测大脑 情绪表达能力下降的负面症状核心领域的电路 社会动力，存在于有精神病风险和病程早期的信息丰富的青少年中。通过应用深层 对啮齿动物进行补充的临床、神经行为、生理和解剖测量的表型分析 研究（项目 II、111）并且可以与细胞、分子和基因组数据集成（项目 IV、V），我们 希望推动这一领域的发展并阐明精神分裂症的关键特征，这些特征需要更好地理解 到新的治疗方法。项目 I 将专门致力于阐明神经反应是如何调节的 厌恶性调节和消退，以及这些过程如何在受影响和处于危险中的青少年中受到损害。 补充脑电图和功能磁共振成像方法将有助于检验杏仁核及其调节失调的假设 在介导负面情绪处理的电路中的作用有助于精神分裂症风险、负面症状、 和社交功能障碍。 样本将包括 225 名具有核心 A 特征的青少年。每组将有 75 名参与者 精神分裂症患者、临床风险和健康对照。他们每人都将接受功能磁共振成像和脑电图检查 以平衡顺序进行实验。探测杏仁核电路的补充任务将是 在研究中进行管理。脑电图程序将包括更精细的计时参数分级和 功能磁共振成像将提供 3D 解剖分辨率以及杏仁核完整性和激活测量。基础和 激活参数将与阴性症状、社会功能的维度测量相关 以及积极和消极价值的社会学习。