Cognitive Enhancement for Persistent Negative Symptoms in Schizophrenia

7.项目总结/摘要 精神分裂症是所有精神疾病中最致残的一种， 对经历这种疾病的个人以及他们的家庭成员和社会的影响。进展 药物治疗和心理社会干预导致住院率大幅下降， 精神病症状，并为受影响的个人提供了机会，使其更加融入社会 社区的成员。尽管取得了这一重大进展，许多精神分裂症患者仍然 明显残疾的持续阴性症状，包括缺乏动力，社会退缩，情绪 迟钝，言语贫乏。这些阴性症状未被当前的药物治疗所治疗， 众所周知，对现有的干预措施反应迟钝，使患者和家庭成员几乎没有 治疗的选择。最近，越来越多的人认识到认知和 精神分裂症的阴性症状和认知补救的心理社会研究已经开始显示， 通过利用计算机和基于小组的练习来治疗阴性症状， 和非社会认知。我们在三个单独的随机化的事后分析中初步观察到- 认知增强疗法（CET）是一种基于证据的认知补救措施， 精神分裂症的治疗方法，可以导致广泛的阴性症状领域的显着减少。此外，本发明还 神经认知和社会认知的改善似乎是这些症状减轻的基础，并指出 认知的增强是治疗阴性症状的最有前途的方法之一， 精神分裂症然而，到目前为止，设计充分的认知补救干预试验还没有 在中度至重度和持续阴性症状的患者中进行，以确认这些效果。 对RFA-MH-18-707“非药物干预的抗炎疗效临床试验”的回复 为精神病患者提供服务”，本项目建议进行一项确定疗效的试验， CET用于治疗有显著和持续阴性症状的精神分裂症患者。共 75名稳定的精神分裂症门诊患者，伴有中度至重度持续性阴性症状， 随机分配至18个月CET或活性强化支持治疗对照组。的全面数据 将事先收集持续阴性症状、社会和非社会认知以及功能结局 治疗和频繁的6个月间隔，以（1）证实CET改善持续性 （2）确认认知目标参与对减少阴性症状的影响; （3）检验CET对阴性症状和功能影响的短期持久性。的结果 该项目预计将为治疗持续性阴性 症状的条件，并显着减少与个人和公共卫生负担 精神分裂症

7. PROJECT SUMMARY/ABSTRACT Schizophrenia is one of the most disabling of all psychiatric conditions, and places significant burden on the individuals who experience the disorder, as well as their family members and society. Advances in pharmacotherapy and psychosocial interventions have led to significant reductions in hospitalization and psychotic symptoms, and have provided opportunities for affected individuals to become more integrated members of the community. Despite this significant progress, many individuals with schizophrenia remain markedly disabled by persistent negative symptoms, including lack of motivation, social withdrawal, emotional blunting, and poverty of speech. These negative symptoms are untreated by current pharmacotherapies and are notoriously unresponsive to existing interventions, leaving patients and family members with little to no options for treatment. Recently, there has been growing appreciation of the overlap between cognitive and negative symptoms in schizophrenia, and psychosocial studies of cognitive remediation have begun to show promise in treating negative symptoms by utilizing computer- and group-based exercises to enhance social and non-social cognition. We have preliminarily observed in post-hoc analyses of three separate randomized- controlled trials that Cognitive Enhancement Therapy (CET), an evidence-based cognitive remediation approach for schizophrenia, can result in significant reductions in broad negative symptom domains. Further, neurocognitive and social-cognitive improvement appear to underlie these symptom reductions, and point to the enhancement of cognition as one of the most promising approaches for treating negative symptoms in schizophrenia. To date, however, adequately designed trials of cognitive remediation interventions have yet to be conducted in patients with moderate-to-severe and persistent negative symptoms to confirm these effects. In response to RFA-MH-18-707, "Confirmatory Efficacy Clinical Trials of Non-Pharmacological Interventions for Mental Disorders", this project proposes to conduct a confirmatory efficacy trial to examine the efficacy of CET for the treatment of schizophrenia patients with significant and persistent negative symptoms. A total of 75 stabilized schizophrenia outpatients with moderate-to-severe persistent negative symptoms will be randomized to 18 months of CET or an active, enriched supportive therapy control. Comprehensive data on persistent negative symptoms, social and non-social cognition, and functional outcome will be collected prior to treatment and at frequent 6-month intervals to (1) confirm the efficacy of CET for improving persistent negative symptoms; (2) confirm the impact of cognitive target engagement on reduced negative symptoms; and (3) examine the short-term durability of CET effects on negative symptoms and functioning. The results of this project are expected to establish promising new avenues for the treatment of persistent negative symptoms in the condition, and to significantly reduce the personal and public health burden associated with schizophrenia.