Neurocognitive function and treatment response in first episode schizophrenia

显著和广泛的认知障碍是精神分裂症的核心特征， 同时作为长期功能结果的可靠预测因子。 最近完成的提高精神分裂症认知能力的测量和治疗研究 （MATRICS）项目展示了NIMH致力于增强我们对认知的理解。 精神分裂症的缺陷在Zucker希尔赛德研究首发精神分裂症的背景下 在医院，神经认知被认为是治疗的关键目标，也被认为是治疗的预测因子或中介因子。 疾病的过程。这个CIDAR项目的主要目的是利用早期神经认知 预测52周对照治疗算法期间功能结局的指标，以及急性 在最初的12周随机临床试验期间的症状反应。与此同时， 在本项目过程中收集的数据也将作为本CIDAR中其他项目的结果变量， 包括项目2（磁共振成像）和项目4（药物基因组学）。 我们将利用MATRICS组合综合评分预测长期（52周）功能结局， 就业、居住状况和社会功能。除了传统的神经心理学 在MATRICS电池的措施，拟议的项目将采用互补的方法，来自 最近的认知神经科学研究这些措施旨在更具体地评估职能 对多巴胺能紧张性和前额皮质-皮质和皮质-皮质下回路的其他方面敏感 对疾病和治疗至关重要。特别是，我们的目标是预测继发于 第二代抗精神病药治疗12周和52周后，使用 一组测试（N-Back工作记忆测试、竞争程序和维度内/维度外集 移位），其已被经验证明对多巴胺操纵和/或COMT敏感 基因型我们还假设，特定的任务挖掘动机和行为生产将预测 阴性症状反应，语义处理措施将预测混乱的症状。 最后，我们将探讨认知的早期变化（基线和12周之间）可能 也可以预测长期反应和结果，只要早期改善可能反映神经 与症状缓解有关的可塑性现象。

Significant and widespread cognitive impairments are a core feature of schizophrenia, providing a window into underlying neuropathophysiology while serving as a robust predictor of long-term functional outcome. The recently completed Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) project demonstrates the commitment of the NIMH to enhancing our understanding of cognitive deficits in schizophrenia. Within the context of research in first episode schizophrenia at the Zucker Hillside Hospital, neurocognition is considered both as a critical target of treatment and as a predictor or mediator of illness course. The primary aims of this proposed CIDAR project involve the use of early neurocognitive measures to predict functional outcome during a 52-week controlled treatment algorithm, as well as acute symptomatic response during the initial 12-week randomized clinical trial. At the same time, measures collected over the course of this project will also serve as outcome variables for other projects in this CIDAR, including Project 2 (Magnetic Resonance Imaging) and Project 4 (Pharmacogenomics). We will utilize the MATRICS battery composite score to predict long-term (52-week) functional outcome in employment, residential status, and social functioning. In addition to the traditional neuropsychological measures in the MATRICS battery, the proposed project will employ complementary methods, derived from recent cognitive neuroscience research. Such measures are designed to more specifically assess functions sensitive to dopaminergic tone and other aspects of prefrontal cortico-cortical and cortico-subcortical circuits critical to illness and treatment. In particular, we aim to predict positive symptom response secondary to dopaminergic modulation by second-generation antipsychotics, after 12- and 52-weeks of treatment, using a set of tests (N-Back working memory test, Competing Programs, and Intradimensional/Extradimensional Set Shifting) that have been empirically demonstrated to be sensitive to dopamine manipulations and/or COMT genotype. We also hypothesize that specific tasks tapping motivation and behavioral production will predict negative symptom response, and semantic processing measures will predict disorganized symptoms. Finally, we will explore the possibility that early changes in cognition (between baseline and 12 weeks) may also be predictors of long term response and outcome, insofar as early improvement may reflect neural plasticity phenomena related to symptom remission.