Neurocognitive function and treatment response in first episode schizophrenia

严重而广泛的认知障碍是精神分裂症的一个核心特征，它提供了一个窗口 神经病理生理学，同时作为长期功能结果的有力预测。 近期完成的提高精神分裂症认知功能的测量和治疗研究 (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 Hillside首发精神分裂症研究的背景下 在医院，神经认知既被认为是治疗的关键目标，也被认为是 病程。这个被提议的CIDAR项目的主要目标包括使用早期神经认知 在52周对照治疗算法中预测功能结果的措施，以及急性 最初为期12周的随机临床试验期间的症状反应。同时，采取措施 在该项目过程中收集的数据也将作为该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)。 我们将使用Matrics电池综合评分来预测长期(52周)的功能结果 就业、居住身份和社会职能。除了传统的神经心理学 在Matrics电池中的措施，拟议的项目将使用补充方法，源自 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 对多巴胺能张力和前额叶皮质和皮质下皮质环路的其他方面敏感 对疾病和治疗至关重要。特别是，我们的目标是预测继发于 第二代抗精神病药物对多巴胺能的调节，在治疗12周和52周后，使用 测试集(N-Back工作记忆测试、竞争程序和传统记忆/外部记忆测试 已被经验证明对多巴胺操作和/或COMT敏感 基因分型。我们还假设，特定的任务开发动机和行为产出将预测 阴性症状反应和语义处理措施将预测混乱的症状。 最后，我们将探索早期认知变化(在基线和12周之间)可能会 也是长期反应和结果的预测指标，因为早期的改善可能反映出神经 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.