Motivational Negative Symptoms in Schizophrenia: Intervention and Biomarkers

 说明： 阴性症状严重干扰日常功能，并导致患有精神分裂症的退伍军人的社区结果不佳。消极症状主要有两种类型：表现性(平淡的情感、冷漠)和动机(悲伤和无社交)。正是这些消极的动机症状干扰了获得和维持工作、形成社会关系[2]和独立生活[3]。精神分裂症的阴性症状被认为是一种未得到满足的治疗需求。他们还为我们提供了一个治疗目标，将极大地改善许多患有SCZ的退伍军人的日常生活。治疗开发是当前提案的主要目标，检查潜在的神经生理生物标记物也是如此。激励性负性症状的生物标志物可以作为临床试验的敏感终点，帮助我们了解激励性负性症状的原因和治疗。目前的CDA提案将在随机对照试验中评估从既定的动机增强(MI)技术改编并以认知-行为方法增强的动机阴性症状治疗的可行性。我将从多个结果领域评估MI的有效性：1)临床评估的动机阴性症状；2)功能结果(社会、工具和独立生活的实际改善)；3)神经生理生物标记物(瞳孔测量和脑电)。退伍军人将被随机分配到MI治疗组或对照组，每周1小时，为期12周。评估组合将在基线、治疗结束时和3个月的随访时进行。在四年的研究中，我们将招募100名患有精神分裂症和高动机负面症状的退伍军人。这项建议旨在检查基于群体的MI对于减少动机消极症状的作用，并利用斜视测量法和EEG来研究动机的生物标志物。预计这种以康复为导向的针对患有失效性动机阴性症状的退伍军人的集体MI治疗将产生结果，为更大规模的治疗试验提供参考，并加强对患有精神分裂症的退伍军人动机阴性症状的神经生理学测量。

 DESCRIPTION: Negative symptoms significantly interfere with daily functioning and contribute to the poor community outcomes of Veterans with schizophrenia. There are two main types of negative symptoms: expressive (flat affect, alogia) and motivational (avolition and asociality). It is the motivational negative symptoms that interfere with obtaining and maintaining employment [1], forming social relationships [2] and living independently [3]. Negative symptoms in schizophrenia are considered an unmet treatment need. They also offer us a treatment target that would vastly improve the daily lives of many Veterans with SCZ. Treatment development is a primary goal of the current proposal, as is the examination of potential neurophysiological biomarkers of motivation. Biomarkers for motivational negative symptoms can be used as sensitive endpoints in clinical trials and can help us understand the causes and treatments of motivational negative symptoms. The current CDA proposal will assess the feasibility of a treatment for motivational negative symptoms adapted from established motivational enhancement (MI) techniques and augmented with cognitive-behavioral approaches, in a randomized controlled trial. I will assess the efficacy of MI with measures from multiple outcome domains: 1) clinically-rated motivational negative symptoms; 2) functional outcomes (real-world improvements in social, instrumental, and independent living); and 3) neurophysiological biomarkers (pupillometry and electroencephalography (EEG)). Veterans will be randomly assigned to the MI treatment or a control treatment for weekly 1-hour sessions for 12 weeks. The assessment battery will be administered at baseline, at completion of treatment, and at 3-month follow-up. We will enroll 100 Veterans with schizophrenia and high motivational negative symptoms across the 4 years of the study. This proposal is designed to examine group-based MI for reducing motivational negative symptoms and investigating biomarkers of motivation with pupillometry and EEG. It is expected that this recovery-oriented group MI treatment for Veterans with disabling motivational negative symptoms will yield results to inform larger treatment trials and enhance neurophysiological measurement of motivational negative symptoms in Veterans with schizophrenia.