Pharmacology of Cognition in Schizotypal Personality

描述(由申请人提供)：拟议的研究旨在利用认知电池来表征与分裂型人格障碍(SPD)相关的认知障碍，包括最近开发的测试，以评估使用鸟嘌呤进行的药物干预对SPD受试者认知功能的影响。这项建议的基础是，SPD患者在警觉性/注意力、编码、工作记忆和情景记忆测试中表现出损害的表现，但在一般智力测试中没有表现出损害，以及鸟嘌呤可以改善注意力缺陷障碍和精神分裂症的认知功能的发现。本研究旨在检验以下基本假设：与健康和其他人格障碍患者对照组相比，SPD患者将表现出实质性的认知障碍：1)听觉和视觉连续操作任务(CPT)以及注意力分离：两种模式的双重任务CPT，2)编码：加利福尼亚言语学习测试(CVLT)和视觉对象学习任务(VET)-第一试验，3)情景记忆：CVLT和VET-Delayed，以及4)工作记忆[N-back CPT，起搏听觉序列加法测试(PASAT，DOT测试)]和干扰(侧翼测试)。有干扰和无干扰的改良A-X CPT也将允许我们测试精神分裂症认知障碍的背景模型和能力模型。此外，基线测试组合中还包括比较措施，假设不同组之间不存在差异，以及假设在基线时区分不同组但不对鸟嘌呤有反应的措施。这些任务将在药物干预之前进行，并在试验期间定期进行双盲随机安慰剂对照试验，所有患者在最后四周内接受药物治疗。据推测，与安慰剂相比，SPD组在这些任务上的表现会有显著的改善，但与安慰剂相比，SPD组的控制任务没有显著的改善。

DESCRIPTION (provided by applicant): The proposed studies are designed to characterize the cognitive impairment associated with schizotypal personality disorder (SPD) using a cognitive battery including recently developed tests to evaluate the effect of a pharmacologic intervention with guanfacine on the cognitive function of SPD subjects. This proposal builds on findings that SPD patients demonstrate impaired performance on tests of vigilance/attention, encoding, working memory, and episodic memory, but not on generalized tests of intelligence as well as findings that guanfacine can improve cognitive function in Attention Deficit Disorder and schizophrenia. This study is designed to test the primary hypotheses that SPD patients will show substantial cognitive impairment compared to healthy and other personality disorder patient comparison groups on: 1) an auditory and visual Continuous Performance Task (CPT) as well as divided attention: the dual task CPT with both modes, 2) encoding: California Verbal Learning Test (CVLT) and Visual Object Learning Task (VOLT) - first trial, 3) episodic memory: CVLT and VOLT - delayed, and 4) working memory [N-back CPT, Paced Auditory Serial Addition Test (PASAT), DOT test], and interference (Flanker test). The modified A-X CPT with and without interference will also allow us to test a context model and a capacity model of cognitive impairment in schizophrenia. In addition, comparison measures are included in the baseline testing battery, which are hypothesized not to differ between groups as well as measures hypothesized to distinguish groups at baseline but not to respond to guanfacine. These tasks will be administered prior to pharmacologic intervention, and during a double-blind randomized placebo-controlled trials of guanfacine at regular intervals during the trial, with all patients receiving medication the last four weeks. It is hypothesized that there wilt be significant improvements in performance on these tasks, but not on the control tasks in the SPD group following active medication compared to placebo with a significant diagnosis by drug interaction in the SPD group compared to the OPD comparison group.