Detecting Which Patients With Schizophrenia Will Improve With Omega 3 Treatment

检测哪些精神分裂症患者可以通过 Omega 3 治疗得到改善

• 批准号: 8532450
• 负责人: DELBERT G ROBINSON
• 金额: $ 25.28万
• 依托单位: FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8532450
• 关键词: Address; Adjuvant; Adverse effects; Animals; Anisotropy; Brain; Brief Psychiatric Rating Scale; Categories; Cell membrane; Characteristics; Chronic; Clinical; Data; Development; Dietary intake; Diffusion Magnetic Resonance Imaging; Double-Blind Method; Enrollment; Erythrocyte Membrane; Family; Goals; Image; Investigation; Legal patent; Link; Measures; Membrane; Myelin; Oligodendroglia; Omega-3 Fatty Acids; Outcome; Outcome Measure; Patients; Peripheral; Phase; Phospholipid Metabolism; Placebos; Play; Randomized; Relative (related person); Research Design; Risperidone; Role; Schizophrenia; Severities; Specificity; Staging; Subgroup; Supplementation; Symptoms; Techniques; Testing; Work; design; improved; in vivo; interest; myelination; patient population; placebo controlled study; primary outcome; public health relevance; response; response marker; standard care; standard measure; white matter

DESCRIPTION (provided by applicant): Omega-3 fatty acids have been used as treatments for schizophrenia with inconsistent results. In particular, studies thus far have used omega-3 treatments for patient groups with broad clinical characteristics, but this broad use may obscure omega-3 effects by including patients who may not ultimately benefit from such treatment. This study will provide the necessary groundwork for determining whether omega-3 treatment should be targeted to more selected patient populations. Erythrocyte membrane omega-3 concentration is a possible response marker given that it has been demonstrated to be abnormal in patients, reflects membrane phospholipid metabolism in the brain and has been linked to long-term outcome in early phase schizophrenia from our pilot data. Moreover, omega-3 fatty acids are essential components of cell membranes and supporting oligodendrocytes and play a critical role in myelination. Animal studies indicate that omega-3 fatty acid supplementation increases brain myelin. In-vivo diffusion tensor imaging (DTI) studies provide strong evidence for abnormalities in white matter integrity in patients with schizophrenia that are associated with worse symptom severity. Interestingly, pilot data from our group indicate that lower peripheral omega-3 concentration is associated with worse white matter integrity in patients, thus laying the groundwork for the proposed study. The specific aims of this study are to: (1) examine the efficacy of omega-3 fatty acids as an adjuvant agent in the treatment of patients with recent-onset schizophrenia; (2) identify whether pretreatment fractional anisotropy assessed by DTI predicts which patients will derive clinical benefit from omega-3 fatty acids; and (3) to identify whether pretreatment peripheral omega-3 fatty acid concentration predicts which patients will derive clinical benefit from omega-3 fatty acids. Exploratory aims included examining whether there is a differential effect of fractional anisotropy versus peripheral omega-3 concentration in predicting response to omega-3 supplementation. The main hypothesis to be tested in this study is that white matter integrity assessed with DTI and erythrocyte membrane omega-3 concentration may provide the means for identifying patients most likely to derive clinical benefit from omega-3 supplementation. To test this hypothesis we will enroll 58 patients with recent-onset schizophrenia into a 4 month long randomized double blind placebo-controlled study of risperidone versus risperidone plus omega-3 supplementation. DTI exams and peripheral omega-3 concentration will be obtained prior to the initiation of treatment and the primary outcome measure will be the total Brief Psychiatric Rating Scale Score. Confirmation of our hypothesis will provide the data required to design a more definitive omega-3 trial using a targeted patient approach with the long-term goal of determining which patients can benefit from omega-3 treatment.

描述（由申请人提供）：omega-3脂肪酸已被用作精神分裂症的治疗方法，结果不一致。特别是，到目前为止，研究对具有广泛临床特征的患者群体使用了omega-3治疗方法，但是这种广泛使用可能会通过包括最终无法从这种治疗中受益的患者来掩盖omega-3的影响。这项研究将为确定欧米茄3治疗是否应针对更多选择的患者人群提供必要的基础。鉴于患者已被证明反映了大脑的膜磷脂代谢，并且与我们的试验数据中的早期精神分裂症相关联，因此红细胞膜omega-3浓度是一种可能的反应标记。此外，omega-3脂肪酸是细胞膜的重要组成部分，并支持少突胶质细胞，并且在髓鞘中起着至关重要的作用。动物研究表明，omega-3脂肪酸补充剂会增加脑髓磷脂。体内扩散张量成像（DTI）研究为精神分裂症患者的白质完整性异常提供了有力的证据 与症状严重程度较差有关。有趣的是，我们组的试点数据表明，较低的外围omega-3浓度与患者的白质完整性较差有关，从而为拟议的研究奠定了基础。这项研究的具体目的是：（1）检查omega-3脂肪酸作为辅助剂在治疗近期患者精神分裂症患者中的功效； （2）确定通过DTI评估的预处理分数各向异性是否可以预测哪些患者将从omega-3脂肪酸中获得临床益处； （3）确定预处理周围omega-3脂肪酸浓度是否预测哪些患者将从omega-3脂肪酸中获得临床益处。探索性目的包括研究分数各向异性与外周omega-3浓度是否存在差异作用，以预测补充omega-3的反应。在这项研究中要检验的主要假设是，用DTI和红细胞膜omega-3浓度评估的白质完整性可能为识别最有可能从补充Omega-3获得临床益处的患者提供了一种手段。为了检验这一假设，我们将58例近期患有精神分裂症的患者进入4个月的4个月随机双盲安慰剂对照研究，对利培酮与利培酮以及补充欧米茄-3的补充。在开始治疗之前将获得DTI检查和外围omega-3浓度，主要结局指标将是总短暂的精神病学评分量表评分。确认我们的假设将提供使用目标患者方法设计更确定的Omega-3试验所需的数据，其长期目标是确定哪些患者可以从Omega-3治疗中受益。