MicroRNAs as Biomarkers in First-episode Schizophrenia

描述（由申请人提供）：这个以指导患者为导向的研究职业发展奖（K23）的目标是为申请人提供必要的培训和支持，使其成为精神分裂症microRNA （miRNA）研究领域的独立研究者。由于mirna能够同时调控多种信使rna的翻译，因此在医学研究中越来越多地用作生物标记物。在精神病学领域，一些研究发现某些mirna（如miR-137和miR-132）与精神分裂症诊断之间存在关联。然而，所有检测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的，也是有趣的。因此，申请人建议研究首发精神分裂症患者脑脊液中miRNA的表达谱，并与健康对照进行比较。对于这个提议，

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.