Selecting Best Neuroleptic Treatment for Veterans with Schizophrenia

为患有精神分裂症的退伍军人选择最佳的抗精神病药物治疗

• 批准号: 8392955
• 负责人: ERIN A. HAZLETT
• 金额: --
• 依托单位: JAMES J PETERS VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8392955
• 关键词: Accounting; Aftercare; Ambulatory Care Facilities; Animal Model; Animals; Antipsychotic Agents; Area; Attention; Automatic Information Processing; Basic Science; Behavioral Paradigm; Benchmarking; Biological; Biological Markers; Blinking; Blood; Brain; Brain imaging; Caring; Clinic; Clinical; Clinical Research; Clinical Treatment; Clinical assessments; Cognitive; Complex; Control Groups; Corpus striatum structure; Data; Data Analyses; Deoxyglucose; Development; Diagnosis; Dopamine D2 Receptor; Dorsal; Early treatment; Elements; Exhibits; Functional Imaging; Functional Magnetic Resonance Imaging; Future; Goals; Head; Health Care Costs; Hospitals; Hour; Human; Individual; Individual Differences; Laboratories; Link; Magnetic Resonance Imaging; Manuscripts; Measures; Medical center; Medicine; Metabolic; Morbidity - disease rate; Neurosciences; New York; Office Visits; Outcome; Participant; Patients; Pharmaceutical Preparations; Positron-Emission Tomography; Principal Investigator; Process; Property; Proxy; Psychiatrist; Psychophysiology; Public Health; Publishing; Recruitment Activity; Relative (related person); Research; Resources; Risperidone; Sample Size; Sampling; Schizophrenia; Sensory; Series; Short-Term Memory; Site; Subgroup; System; Techniques; Testing; Therapeutic; Time; Translating; Treatment Failure; Ursidae Family; Veterans; Work; Writing; attentional modulation; base; bench to bedside; blink reflexes; caudate nucleus; clinical care; clinical practice; comparison group; cost; cost effective; design; evidence base; follow-up; frontal lobe; information processing; innovation; interest; neurobiological mechanism; neuroimaging; novel; prepulse inhibition; prevent; programs; receptor; response; tool; treatment duration; treatment response; treatment trial; trend; trial comparing; week trial

DESCRIPTION (provided by applicant): The proposed research has the primary goal of beginning to translate basic and clinical research into innovative clinical assessment and therapeutics. Functional brain imaging, as well as, animal 2-deoxyglucose studies have demonstrated that antipsychotic drugs have robust effects on striatal activity. This project is a follow-up to a series of studies of ours and others that have found low relative metabolic rates in the striatum as assessed by 18-F-2-deoxyglucose positron emission tomography (FDG-PET) to predict antipsychotic response. We will acquire fMRI and sensorimotor gating (passive- and active-attention prepulse inhibition (PPI) of startle) in a large sample of unmedicated schizophrenia patients (n=64; plus an additional 16 patients to allow for 20% attrition) at baseline (Day 0) and at the end of a 4-week risperidone treatment trial. Using fMRI, this project will extend earlier FDG-PET studies which showed low dorsal caudate activity predicts antipsychotic response. We will also obtain fMRI and PPI measures in a healthy-control group (n=32; plus 3 for attrition) as a benchmark for comparing whether caudate and PPI activity is more normalized with risperidone treatment in the responder subgroup compared with the treatment non-responder subgroup. Our pilot data suggest that PPI measures are a potential proxy for caudate function and may eventually serve as useful intermediary treatment predictors. We also have new pilot data indicating that low caudate activity measured with fMRI and poor PPI show a trend for predicting better response to a 4-week risperidone trial in schizophrenia patients. We anticipate that this project will take four years: three months for startup, 39 months for patient and healthy control comparison group acquisition, and 6 months for data analysis and writing scientific manuscripts. The project will be conducted at the James J. Peters VA Medical Center and involve patients recruited from three sites: the James J. Peters and New York Harbor VA Medical Centers, and Mount Sinai Hospital (J.J. Peters VAMC affiliate). Approximately two-thirds of the patient sample will be recruited, diagnosed and treated at the J.J. Peters VAMC. One-third of the patient sample will be recruited from the NY Harbor VAMC and patients from Mount Sinai will be recruited for attrition purposes only. Healthy controls will be recruited from the James J. Peters VAMC. The fMRI and psychophysiological testing sessions will take place at Mount Sinai for all study participants where a state-of-the-art head-dedicated 3T MRI scanner and the Cognitive Psychophysiology Laboratory are located. The primary objective of the proposed research is to begin to identify potential biomarkers for predicting antipsychotic treatment response in patients with schizophrenia. Currently, there is no biological marker to assist psychiatrists in determining which antipsychotic medication will give the optimal response in a given patient. Instead, the selection of an antipsychotic medication for a particular patient involves a complex trial- and-error process. Demonstration of the usefulness of caudate and sensorimotor gating measures as biomarkers for predicting treatment response in schizophrenia patients could bring ecologically-valid tools from bench to bedside.

描述（由申请人提供）： 拟议研究的主要目标是将基础和临床研究转化为创新的临床评估和治疗方法。功能性脑成像以及动物 2-脱氧葡萄糖研究表明，抗精神病药物对纹状体活动具有强大的影响。该项目是我们和其他人进行的一系列研究的后续研究，这些研究发现，通过 18-F-2-脱氧葡萄糖正电子发射断层扫描 (FDG-PET) 评估，纹状体的相对代谢率较低，可预测抗精神病药物的反应。我们将在未接受药物治疗的精神分裂症患者的大样本（n=64；加上另外 16 名患者，以允许 20% 的损耗）中获得基线时的 fMRI 和感觉运动门控（惊吓的被动和主动注意前脉冲抑制 (PPI)）（第 0 天）和 4 周利培酮治疗试验结束时。利用功能磁共振成像，该项目将扩展早期的 FDG-PET 研究，该研究显示低背侧尾状核活动可预测抗精神病药物的反应。我们还将获得健康对照组（n=32；加上 3 表示损耗）的 fMRI 和 PPI 测量值，作为比较有反应亚组中利培酮治疗与非治疗组尾状核和 PPI 活性是否更正常化的基准。响应者亚组。 我们的试点数据表明，PPI 测量是尾状核功能的潜在指标，并且最终可能作为有用的中间治疗预测因子。我们还有新的试点数据表明，通过 fMRI 测量的低尾状核活动和较差的 PPI 显示出一种趋势，可以预测精神分裂症患者对为期 4 周的利培酮试验有更好的反应。我们预计这个项目将需要四年的时间：启动三个月，获取患者和健康对照组对照组需要 39 个月，数据分析和撰写科学手稿需要 6 个月。该项目将在 James J. Peters VA 医疗中心进行，涉及从三个地点招募的患者：James J. Peters 和纽约港 VA 医疗中心以及西奈山医院（J.J. Peters VAMC 附属机构）。大约三分之二的患者样本将在 J.J. 医院进行招募、诊断和治疗。彼得斯·VAMC。三分之一的患者样本将从纽约港 VAMC 招募，而西奈山的患者仅出于自然减员目的而招募。健康对照将从 James J. Peters VAMC 招募。功能磁共振成像和心理生理学测试课程将在西奈山为所有研究参与者进行，那里设有最先进的头部专用 3T MRI 扫描仪和认知心理生理学实验室。 拟议研究的主要目的是开始识别潜在的生物标志物，用于预测精神分裂症患者的抗精神病药物治疗反应。目前，没有生物标志物可以帮助精神科医生确定哪种抗精神病药物会对特定患者产生最佳反应。相反，为特定患者选择抗精神病药物涉及复杂的试错过程。证明尾状核和感觉运动门控测量作为预测精神分裂症患者治疗反应的生物标志物的有用性可以将生态上有效的工具从实验室带到临床。