Pharmacology of Cognition in Schizotypal Personality Disorder

描述（由申请人提供）：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，在听觉和视觉空间模式下评估Baddeley综合模型所描述的操作和维持成分，(2)反映加工能力的多模态双任务信息加工任务，(3)标准情境加工依赖工作记忆任务。(4)基于表现的功能能力测量；(5)情景记忆和工作记忆任务的标准化测试。在60名SPD患者和60名非精神分裂症相关人格障碍、回避型人格障碍（AvPD）患者进行为期4周的胍法辛双盲安慰剂对照试验后，这些任务将在基线和4周后进行评估。这些任务也将在60名健康对照者的基线和4周后进行评估。假设SPD患者将表现出中央执行功能（维持加操纵）的损害，与AvPD患者和健康对照（HC）组相比，其仅维持的表现不成比例，类似于先前在精神分裂症患者中发现的结果。与AvPD相比，SPD的双重任务处理（时间分配）将明显受损，并且与其他中央执行措施类似，对胍法辛治疗有反应。假设胍法辛会改善Cannon-Glahn任务的工作记忆表现，特别是在中央执行领域（即操作和上下文处理），但与安慰剂相比不会改善情景记忆。也有假设认为SPD患者基于性能的功能能力测量会受损，并且在胍法辛治疗后会得到改善。这些研究将更具体地描述工作记忆的损害，这似乎是造成精神分裂症谱系障碍认知障碍的主要原因，并评估胍法辛药物干预对SPD患者工作记忆的影响。在短时间内记忆信息的困难是精神分裂症患者职业和社会问题的一个重要因素。这些研究将有助于澄清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种问题。

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.