Pharmacology of Cognition in Schizotypal Personality Disorder

描述(申请人提供)：拟议的研究旨在具体评估：(1)与分裂型人格障碍(SPD)相关的工作记忆障碍，评估Baddeley综合模型中在听觉和视觉空间模式下描述的操作和维护的组成部分，(2)反映处理能力的多模式双重任务信息处理任务，(3)标准的上下文加工依赖的工作记忆任务，(4)基于表现的功能能力测量，以及(5)标准化的情景记忆和工作记忆任务组合。这些任务将在基线和对60名SPD患者和60名非精神分裂症相关人格障碍--回避性人格障碍(AvPD)患者进行双盲安慰剂对照试验4周后进行评估。这些任务也将在基线时和4周后在60名健康对照组中进行评估。假设与AvPD和健康对照(HC)组相比，SPD患者将表现出与其仅维持功能不成比例的中枢执行功能损害(维持和操作)，类似于先前在精神分裂症患者中发现的结果。与AvPD相比，SPD患者的双重任务处理(分时)明显受损，并且与其他中央执行措施类似，对愈创新的治疗也有反应。据推测，与安慰剂相比，金刚烷素可以改善Cannon-Glahn任务的工作记忆成绩，特别是在中央执行(即操纵和语境处理)领域，但不会改善情节记忆。它还假设，在SPD患者中，基于绩效的功能能力测量将受到损害，并将通过愈创新治疗而改善。这些研究将更具体地描述工作记忆受损的特征，这种损害似乎是精神分裂症谱系障碍认知障碍的主要原因，并评估鸟嘌呤类药物干预对SPD患者工作记忆的影响。短期记忆困难是导致精神分裂症患者职业和社会问题的一个重要因素。这些研究将有助于阐明这种记忆问题的确切性质，并研究如何通过药物治疗来改善这一问题。

DESCRIPTION (provided by applicant): The proposed study is designed to specifically evaluate: (1) the working memory impairment associated with schizotypal personality disorder (SPD), assessing components of manipulation and maintenance as delineated in Baddeley's comprehensive model in both auditory and visuospatial modes, (2) a multimodal dual task information processing task reflecting processing capacity, (3) a standard context-processing dependent working memory task , (4) performance-based measures of functional capacity and (5) a standardized battery of episodic memory and working memory tasks. These tasks will be evaluated at baseline and after 4 weeks of a double blind placebo controlled trial of guanfacine in 60 patients with SPD and 60 patients with a non-schizophrenia related personality disorder, avoidant personality disorder (AvPD). These tasks will also be evaluated at baseline in 60 healthy controls and 4 weeks later. It is hypothesized that SPD patients will demonstrate impairment in central executive functions (maintenance plus manipulation) that is disproportionate to their maintenance only performance compared to the patients with AvPD and healthy control (HC) groups, similar to previous results found in schizophrenic patients. Dual task processing (time sharing) will be markedly impaired in SPD as compared to AvPD and, similar to other central executive measures, responsive to treatment with guanfacine. It is hypothesized that guanfacine will improve working memory performance on the Cannon-Glahn tasks particularly in the realm of central executive (i.e. manipulation and context processing), but will not improve episodic memory compared to placebo. It is also hypothesized that performance-based measures of functional capacity will be impaired in SPD patients and will improve with guanfacine treatment. These studies will more specifically characterize the impairment in working memory that appears to account for much of the cognitive impairment of the schizophrenia spectrum disorders and to evaluate the effects of a pharmacologic intervention with guanfacine on working memory in SPD patients. Difficulty in holding information in memory over short periods of time is an important contributor to the occupational and social problems of individuals with the schizophrenic disorders. These studies will help to clarify the exact nature of this memory problem and investigate how it can be improved by medication treatment.