MicroRNAs as Biomarkers in First-episode Schizophrenia

MicroRNA 作为首发精神分裂症的生物标志物

• 批准号: 8643293
• 负责人: Juan Andres Gallego
• 金额: $ 18万
• 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: 2013-04-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8643293
• 关键词: Adverse effects; Affect; Antipsychotic Agents; Autopsy; Binding; Bioinformatics; Biological Markers; Bipolar Disorder; Blood specimen; Brain; Cerebrospinal Fluid; Clinic; Complex; Data; Data Analyses; Development; Diagnosis; Diagnostic; Disease; Enrollment; Examinations and Diagnoses; Functional disorder; Future; Genes; Goals; Hereditary Disease; Human; Institution; Introns; Knowledge; Link; Medical Research; Mentored Patient-Oriented Research Career Development Award; Mentorship; Messenger RNA; MicroRNAs; Molecular Biology; Molecular Profiling; National Institute of Mental Health; Neurocognitive; Nucleotides; Other Genetics; Pathway Analysis; Patient Self-Report; Patients; Physicians; Pilot Projects; Post-Transcriptional Regulation; Process; Psychiatry; Psychopathology; RNA; Recruitment Activity; Reporting; Research; Research Infrastructure; Research Personnel; Resources; Risperidone; Role; Sampling; Schizophrenia; Scientist; Sequence Analysis; Single Nucleotide Polymorphism; Spinal Puncture; Statistical Methods; Testing; Training Activity; Training Support; Transcript; Translational Research; Translations; United States National Institutes of Health; Weight Gain; base; brain tissue; clinical practice; experience; first episode schizophrenia; genome wide association study; genome-wide; healthy volunteer; improved; in vivo; mental state; neuroimaging; novel; oncology; peripheral blood; programs; psychogenetics; public health relevance; success; translational approach; treatment response

DESCRIPTION (provided by applicant): The goal of this Mentored Patient Oriented Research Career Development Award (K23) is to provide the applicant with the training and support necessary to become an independent investigator in the field of microRNA (miRNA) research in schizophrenia. MiRNAs are increasingly used as biological markers in medical research due to their capacity to simultaneously regulate the translation of multiple messenger RNAs. In the field of psychiatry, several studies have found associations between certain miRNAs, such as miR-137 and miR-132, and schizophrenia diagnosis. However, all human studies that have examined miRNA expression profiles have done so in post-mortem brain tissue or peripheral blood. However, given the intimate relationship between brain and cerebrospinal fluid, the use of cerebrospinal fluid to investigate the role of miRNAs in schizophrenia is logical and intriguing Therefore, the applicant proposes to investigate miRNA expression profiles in cerebrospinal fluid in first-episode schizophrenia patients in comparison to healthy controls. For this proposal, the applicant plans to recruit first-episode patients who have been exposed to antipsychotics for less than 16 weeks and who are initiating manualized treatment with risperidone as part of their enrollment in a clinic specialized in treatment of first-episode schizophrenia patients. For these subjects, a lumbar puncture will be obtained upon enrollment. Psychopathology and side effect assessments will be conducted weekly for 4 weeks and then every two weeks until patients complete 16 weeks of risperidone treatment. The primary aims for this application are: 1) to conduct miRNA sequencing in cerebrospinal fluid samples from first-episode patients and healthy volunteers to test the hypothesis that significant number of miRNAs will be dysregulated in first-episode schizophrenia; 2) To determine whether certain miRNAs can help as predictive biomarkers in relationship to treatment response and/or development of side effects, especially weight gain. To accomplish these aims, a comprehensive didactic program has been prepared to help the primary investigator gain knowledge about the molecular biology of miRNAs, the use of miRNAs as predictive biomarkers and the advanced statistical methods used for miRNA sequencing data analysis. The completion of the proposed study, the training activities described in this application, the outstanding mentorship team plus the institutional resources will allow the applicant to become a successful independent investigator, with expertise in miRNA research in schizophrenia. This is in alignment with the NIH goal of recruiting more physician scientists involved in translational research.

描述（由申请人提供）：该指导性患者导向研究职业发展奖（K23）的目标是为申请人提供成为精神分裂症 microRNA (miRNA) 研究领域的独立研究者所需的培训和支持。由于能够同时调节多个信使 RNA 的翻译，miRNA 越来越多地被用作医学研究中的生物标记。在精神病学领域，多项研究发现某些 miRNA（例如 miR-137 和 miR-132）与精神分裂症诊断之间存在关联。然而，所有检查 miRNA 表达谱的人类研究都是在死后脑组织或外周血中进行的。然而，考虑到大脑和脑脊液之间的密切关系，利用脑脊液来研究miRNA在精神分裂症中的作用是合乎逻辑且有趣的。因此，申请人建议研究首发精神分裂症患者脑脊液中的miRNA表达谱，并与健康对照进行比较。对于这个提案， 申请人计划招募接触抗精神病药物时间少于16周且正在开始利培酮手动治疗的首发患者，作为其在专门治疗首发精神分裂症患者的诊所入组的一部分。对于这些科目，将在入学时进行腰椎穿刺。精神病理学和副作用评估将每周进行一次，持续 4 周，然后每两周进行一次，直到患者完成 16 周的利培酮治疗。该应用的主要目的是：1）对首发患者和健康志愿者的脑脊液样本进行 miRNA 测序，以检验首发精神分裂症中大量 miRNA 失调的假设； 2) 确定某些 miRNA 是否可以作为与治疗反应和/或副作用发生（尤其是体重增加）相关的预测生物标志物。为了实现这些目标，我们准备了一个全面的教学计划，以帮助主要研究者获得有关 miRNA 分子生物学、使用 miRNA 作为预测生物标志物以及用于 miRNA 测序数据分析的高级统计方法的知识。拟议研究的完成、本申请中描述的培训活动、优秀的指导团队加上机构资源将使申请人成为一名成功的独立研究者，拥有精神分裂症 miRNA 研究的专业知识。这符合美国国立卫生研究院招募更多医师科学家参与转化研究的目标。