Development Trajectories of Negative Symptoms in Schizophrenia

精神分裂症的阴性症状对治疗提出了挑战，并与严重的 功能障碍。描述这些症状的发展轨迹及其与 精神分裂症和精神病在青春期和成年早期的出现是必不可少的 早期识别和临床干预的前提条件。这个项目的总体目标是探索大脑 构成情绪表现力减弱和消极症状的核心领域的回路 社会动力，在有精神病风险和病程早期的信息丰富的青年中。通过应用深度 补充啮齿动物的临床、神经行为、生理和解剖学指标的表型 研究(项目二、111)，并可与细胞、分子和基因组数据结合(项目四、五)，我们 希望推动这一领域并阐明精神分裂症的关键特征，这些特征需要更好的理解领导 为新疗法干杯。项目I将特别致力于阐明神经反应是如何通过 厌恶的条件反射和消退，以及这些过程在受影响和处于危险中的青少年中是如何受损的。 互补的EEG和fMRI方法将有助于检验以下假设：amgydala和其 在介导负面情绪处理的回路中的作用有助于精神分裂症的风险，负面症状， 和社交功能障碍。 样本将包括225名以核心A为特征的青年，每组75名参与者。 精神分裂症患者、临床危险因素和健康对照。他们每个人都将接受功能磁共振成像和脑电波检查 以一种平衡的顺序进行实验。探测杏仁核回路的补充任务将是 在研究中使用。EEG程序将包括更精细的定时参数分级和 功能磁共振成像将提供3D解剖分辨率以及杏仁核的完整性和激活措施。基本和 激活参数将与阴性症状、社会功能的维度测量相关 和社会学习的积极和消极的价值。

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.