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，为了解潜在的神经病理生理学提供了一个窗口，同时也是长期功能结局的可靠预测因子。 最近完成的测量和治疗研究，以提高认知精神分裂症（MATRICS）项目表明，NIMH的承诺，以提高我们对认知缺陷的理解精神分裂症。在Zucker希尔赛德医院对首发精神分裂症的研究中，神经认知被认为是治疗的关键目标，也是精神分裂症的预测因子或中介因子。 疾病的过程。这个拟议的CIDAR项目的主要目的涉及使用早期神经认知测量来预测52周对照治疗算法期间的功能结局，以及最初12周随机临床试验期间的急性症状反应。同时，在本项目过程中收集的测量数据也将作为本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组合综合评分预测就业、居住状况和社会功能的长期（52周）功能结局。除了传统的神经心理学措施在矩阵电池，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。这些措施的目的是更具体地评估功能敏感的多巴胺能紧张和其他方面的前额叶皮质-皮质和皮质-皮质下电路的疾病和治疗的关键。特别是，我们的目标是预测继发于 在治疗12周和52周后，使用一组试验（N-Back工作记忆试验、竞争程序和维度内/维度外集合移位），通过第二代抗精神病药调节多巴胺能，这些试验已被经验证明对多巴胺操作和/或COMT基因型敏感。我们还假设，特定的任务挖掘动机和行为生产将预测消极的症状反应，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）也可能是长期反应和结果的预测因子，因为早期改善可能反映与症状缓解相关的神经可塑性现象。

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.