Proof of concept study of negative symptoms in schizophrenia

项目2中计划进行概念验证研究，该研究将检查新药探针对 与精神分裂症认知表型和阴性症状表型相关的生物标志物。 参与者将是精神分裂症先证者的亲属，他们显示出精神分裂症易感性的证据， 精神分裂症谱系人格特征和视觉空间工作能力差的存在表明 记忆这些研究提供了一种手段来确定一种药物的潜在功效的早期人类信号。 用于精神分裂症认知和/或阴性症状的化合物。有几个优点， 拟议的研究设计，招募生物标志物阳性的参与者，而没有全面的 精神分裂症这些研究将允许评价新的药理学药剂对 孤立的生理缺陷，缺乏当前或过去抗精神病药物的影响，明显的精神病， 以及可能使治疗相关的认知“信号”模糊或调节的一般性认知缺陷。 提出了两项研究，将检查催产素和烟碱激动剂DMXB-A对 一系列生物标志物。我们将检验催产素将有益于阴性症状表型的假设 证实了显着改善措施的社会驱动力，嗅觉，面部情感识别，顺利 内部驱动的眼跳的追踪眼动启动和潜伏期。DMXB-A将有利于认知， 证实了显着改善视觉空间工作记忆，处理速度，言语情节 记忆、P50感觉门控和预测追踪眼动增益。

Proof-of-concept studies are planned in Project #2 that will examine the effects of novel drug probes on the biomarkers associated with schizophrenia cognitive phenotype and negative symptom phenotype. Participants will be relatives of schizophrenia probands who show evidence of schizophrenia liability as suggested by the presence of schizophrenia spectrum personality traits and poor visuo-spatial working memory. These studies provide a means of ascertaining an early human signal of potential efficacy of a compound for schizophrenia cognition and/or negative symptoms. There are several advantages to the proposed study design that recruits participants who are positive for biomarkers without having the full-blown schizophrenia. These studies will allow evaluation of the effects of the novel pharmacological agents on the physiological deficit in isolation, absent the effects of current or past antipsychotic drugs, overt psychosis, and generalized cognitive deficits that may cloud or modulate the treatment related cognitive "signal". Two studies are proposed that will examine the effects of oxytocin and a nicotinic agonist, DMXB-A, on a battery of biomarkers. We will test the hypothesis that oxytocin will benefit negative symptom phenotype confirmed by significant improvements in measures of social drive, olfaction, facial affect recognition, smooth pursuit eye movement initiation and latency of internally-driven saccades. DMXB-A will benefit cognition as confirmed by significant improvements in visuo-spatial working memory, processing speed, verbal episodic memory, P50 sensory gating, and predictive pursuit eye movement gain.