Tretment of negative symptoms and cognitive impairment in schizoprenia

精神分裂症患者的特征是一系列症状，包括阴性症状。 和认知障碍。精神病理学的这两个领域是导致功能低下的主要原因 结果。这些领域的抗精神病药物疗效充其量是适度的，有时甚至是不利的。在 Matrics过程中，业界达成共识，认为这两大领域是关键未满足的 治疗目标，这两个领域的新药发现是至关重要的。我们将进行一项 平行组，催产素和DMXB-A的安慰剂对照比较。这项研究将使用双假人 设计，为期4周的持续稳定(导入)阶段和6周的双盲治疗阶段。那里 每个治疗臂将有40名受试者。受试者将表现出最低水平的持续性负面情绪 症状，并判断尽管接受了治疗，但阴性症状在临床上是显著的。科目 将被判定为临床稳定，不会超过阳性、抑郁和/或 锥体外系症状。拟议的研究将涉及以下两个主要目标：1)确定 辅助催产素对持续性阴性症状的治疗是否优于安慰剂，如 在精神分裂症患者中，通过SANS总分来衡量；以及2)以确定是否存在附属症状 DMXB-A在治疗认知障碍方面优于安慰剂，从以下方面衡量 综合神经认知评分(源自加工速度(BAG)、情景记忆(HVLT)、 精神分裂症患者的注意力(RVIP))。此外，这项研究还将涉及以下次要问题 目的：1)确定精神分裂症患者接受辅助催产素治疗是否与 安慰剂将在阴性症状责任的表型标记物上显示出更大的改善，包括：社交 从属关系、面部情感识别、嗅觉辨别、平稳追求的启动和潜伏期 内部驱动的眼跳；以及2)确定精神分裂症患者是否接受了辅助性治疗 与安慰剂相比，DMXB-A在认知表型标记方面将显示出更大的改善 损害倾向包括：预测性追踪、P50感觉门控和视觉空间工作记忆。这个 这项研究还将提供数据，以确定药物效果之间的关系， 非临床人体和临床试验模型。

People with schizophrenia are characterized by a broad range of symptoms, including negative symptoms and cognitive impairments. These two domains of psychopathology are the major causes of poor functional outcome. Antipsychotic efficacy for these domains is modest at best and sometimes adverse. In the MATRICS process, the field reached a consensus that these domains are the two major critical unmet therapeutic targets, and that new drug discovery for these two domains was essential. We will conduct a parallel group, placebo-controlled comparison of oxytocin and DMXB-A. The study will use a double-dummy design, with a 4-week continued stability (lead-in) phase and a 6-week double-blind treatment phase. There will be 40 subjects in each treatment arm. Subjects will demonstrate a minimum level of persistent negative symptoms, with a judgment that the negative symptoms are clinically significant despite treatment. Subjects will be judged clinically stable and will not exceed threshold levels of positive, depressive, and/or extrapyramidal symptoms. The proposed study will address the following two primary aims: 1) to determine whether adjunctive oxytocin is superior to placebo for the treatment of persistent negative symptoms, as measured by the SANS total score, in people with schizophrenia; and 2) to determine whether adjunctive DMXB-A is superior to placebo for the treatment of cognitive impairments, as measured by improvement on a composite neurocognitive score (derived from processing speed (BAGS), episodic memory (HVLT), attention (RVIP)), in people with schizophrenia. In addition, the study will address the following secondary aims: 1) to determine whether people with schizophrenia treated with adjunctive oxytocin, compared to placebo, will show greater improvement on phenotypic markers of negative symptom liability including: social affiliation, facial affect recognition, olfactory discrimination, initiation of smooth pursuit and latency of internally-driven saccades; and 2) to determine whether people with schizophrenia treated with adjunctive DMXB-A, compared to placebo, will show greater improvement on phenotypic markers of cognitive impairment liability including: predictive pursuit, P50 sensory gating and visuo-spatial working memory. The study will also provide data for the determination of the relationship of drug effects across the pre-clinical, non-clinical human, and clinical trial models.