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.

Public Health Relevance

The diagnosis and treatment of schizophrenia poses many challenges given the lack of clinically useful biological markers. In this study, we plan to study microRNAs in cerebrospinal fluid in first-episode schizophrenia patients compared to healthy volunteers with the goal to assess the utility of microRNAs as a biomarker. Results of this project may provide a basis to better understand the pathophysiology and improve the diagnosis and treatment of this illness in the near future.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
Application #
Study Section
Adult Psychopathology and Disorders of Aging Study Section (APDA)
Program Officer
Chavez, Mark
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Feinstein Institute for Medical Research
United States
Zip Code
Blanco, Emily A; Duque, Laura M; Rachamallu, Vivekananda et al. (2018) Predictors of aggression in 3.322 patients with affective disorders and schizophrenia spectrum disorders evaluated in an emergency department setting. Schizophr Res 195:136-141
Lyall, A E; Pasternak, O; Robinson, D G et al. (2018) Greater extracellular free-water in first-episode psychosis predicts better neurocognitive functioning. Mol Psychiatry 23:701-707
Sarpal, Deepak K; Argyelan, Miklos; Robinson, Delbert G et al. (2016) Baseline Striatal Functional Connectivity as a Predictor of Response to Antipsychotic Drug Treatment. Am J Psychiatry 173:69-77
Patel, Ekta; Gallego, Juan A (2016) Bilateral cataracts in a young patient with bipolar disorder on treatment with risperidone. Aust N Z J Psychiatry 50:1210
Robinson, Delbert G; Gallego, Juan A; John, Majnu et al. (2015) A Randomized Comparison of Aripiprazole and Risperidone for the Acute Treatment of First-Episode Schizophrenia and Related Disorders: 3-Month Outcomes. Schizophr Bull 41:1227-36
Trampush, Joey W; Lencz, Todd; DeRosse, Pamela et al. (2015) Relationship of Cognition to Clinical Response in First-Episode Schizophrenia Spectrum Disorders. Schizophr Bull 41:1237-47
Zhang, Jian-Ping; Robinson, Delbert G; Gallego, Juan A et al. (2015) Association of a Schizophrenia Risk Variant at the DRD2 Locus With Antipsychotic Treatment Response in First-Episode Psychosis. Schizophr Bull 41:1248-55
Gallego, Juan A; Rachamallu, Vivekananda; Yuen, Eunice Y et al. (2015) Predictors of suicide attempts in 3.322 patients with affective disorders and schizophrenia spectrum disorders. Psychiatry Res 228:791-796