Proof of concept study of negative symptoms in schizophrenia

概念验证研究计划在项目2中进行，该研究将检查新型药物探测器对 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，他们有精神分裂症倾向的证据 由精神分裂症谱系的存在、人格特征和视觉空间工作不良所提示 记忆。这些研究提供了一种方法，以确定早期人类信号的潜在疗效 治疗精神分裂症认知和/或阴性症状的化合物。这样做有几个优点 建议的研究设计，招募生物标记物呈阳性但尚未完全发育成熟的参与者 精神分裂症。这些研究将使评估新的药理制剂对 孤立的生理缺陷，没有当前或过去的抗精神病药物的影响，明显的精神病， 以及可能影响或调节与治疗相关的认知“信号”的全面性认知缺陷。 建议进行两项研究，以考察催产素和尼古丁激动剂DMXB-A对 一组生物标志物。我们将检验催产素将有益于阴性症状表型的假设 在社交动力、嗅觉、面部情感识别、顺畅 追踪性眼动启动和内驱性眼跳的潜伏期。DMXB-A将使认知受益，因为 在视觉空间工作记忆、处理速度、言语片段等方面的显著改善证实了这一点 记忆、P50感觉门控和预测性追踪眼动增益。

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.