Tretment of negative symptoms and cognitive impairment in schizoprenia

精神分裂症患者的特征是广泛的症状，包括阴性症状 和认知障碍。精神病理学的这两个领域是功能不良的主要原因。 结果。这些领域的抗精神病疗效最好是适度的，有时是不利的。在 MATRICS过程中，该领域达成了共识，认为这两个领域是关键的未满足的 治疗靶点，这两个领域的新药开发至关重要。我们将进行 催产素和DMXB-A的平行组、安慰剂对照比较。本研究将使用双假人 设计，包括4周的持续稳定（导入）期和6周的双盲治疗期。那里 每个治疗组将有40例受试者。受试者将表现出最低水平的持续阴性 症状，判断阴性症状在治疗后仍具有临床意义。科目 将被判定为临床稳定，并且不会超过阳性、抑郁和/或 锥体外系症状拟议的研究将针对以下两个主要目标：1）确定 对于持续性阴性症状的治疗，催产素是否上级安慰剂， 通过SANS总分测量，在精神分裂症患者中;以及2）确定是否有 DMXB-A在治疗认知障碍方面上级安慰剂， 复合神经认知评分（源自处理速度（BAGS），情景记忆（HVLT）， 注意力（RVIP））。此外，该研究还将探讨以下次级问题： 目的：1）确定精神分裂症患者是否接受催产素治疗， 在阴性症状倾向的表型标志物上显示更大的改善，包括： 依恋、面部情感识别、嗅觉辨别、平滑追踪的启动和 内部驱动的扫视;和2）以确定是否与精神分裂症治疗的人， 与安慰剂相比，DMXB-A将显示出对认知障碍的表型标志物的更大改善。 损害倾向包括：预测追踪，P50感觉门控和视觉空间工作记忆。的 本研究还将提供数据，用于确定临床前， 非临床人类和临床试验模型。

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.