Developing Alternative Diagnostic Pathways Dysregulation of micro-RNAs in neurodevelopment as a predictive mechanism for diagnosing schizophrenia.

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Presentation transcript:

Developing Alternative Diagnostic Pathways Dysregulation of micro-RNAs in neurodevelopment as a predictive mechanism for diagnosing schizophrenia

What is Schizophrenia Schizophrenia is a neuropsychiatric disorder characterized by abnormalities of the nervous system Visual Hallucinations Verbal Hallucinations Paranoia

Misdiagnose of Schizophrenia among minorities Issue Minorities less likely to be diagnosed with mood disorder Minorities more likely to be diagnosed with Psychotic disorders Clinician bias due to stereotyping Sides Effects Of Medication Restlessness Tremors Muscle Spasms

Questions? Can we effectively measure mi-RNA expression levels from samples taken from the prefrontal cortex, and can we translate this into a diagnostic tool?

MicroRNA Functions MiRNA Cleavage MiRNA Translational Repression

Microarray Normal Tissue SampleAbnormal Tissue Sample mRNA Addition of Buffers to Extract mRNA

Gel Electrophoresis

Isolating MicroRNA for a Microarray Addition of our dye’s Poly(A) Polymerase Labeling Pipet into Microarray Shingara et. al. Method

Detection

Can we use MicroRNA expressions levels to diagnose Schizophrenia? BenefitLimitations Quantitative Analysis (Schizophrenia with False Discovery Rate Factored In) Verification with QPCR (Con-Control, SCZ-schizophrenia for miR- 132) Must be less than 0.05 to be significant

References Ambros, V. (January 01, 2001). microRNAs:Tiny Regulators with Great Potential. Cell,107, 7, Barnes, A. (January 01, 2008). Race and Hospital Diagnoses of Schizophrenia and Mood Disorders. Social Work, 53, 1, Calin, G. A., & Croce, C. M. (January 01, 2006). MicroRNA signatures in human cancers. Nature Reviews. Cancer, 6, 11, Chekanova, J. A., & Belostotsky, D. A. (January 01, 2006). MicroRNAs and messenger RNA turnover. Methods in Molecular Biology (clifton, N.j.), 342, National Institute of Mental Health (U.S.). (2008). Mental health medications. Rockville, Md.: National Institute of Mental Health, U.S. Dept. of Health and Human Services, National Institutes of Health. Li, F., & Tsien, J. Z. (July 16, 2009). Memory and the NMDA Receptors. New England Journal of Medicine, 361, 3, Miller, B. H., Zeier, Z., Xi, L., Lanz, T. A., Deng, S., Strathmann, J., Willoughby, D.,... Wahlestedt, C. (January 01, 2012). MicroRNA-132 dysregulation in schizophrenia has implications for both neurodevelopment and adult brain function. Proceedings of the National Academy of Sciences of the United States of America, 109, 8, Mukherjee, S., Shukla, S., Woodle, J., Rosen, A. M., & Olarte, S. (January 01, 1983). Misdiagnosis of schizophrenia in bipolar patients: a multiethnic comparison. The American Journal of Psychiatry, 140, 12, Oxford University Press. (2007). Concise colour medical dictionary. Oxford: Oxford University Press. miRVANA miRNA Isolation Kit Ambion RNA by Life Technologies flashpage reaction cleaup kit Ambion Applied Biosystems SHINGARA, JACLYN, KEIGER, KERRI, SHELTON, JEFFREY, LAOSINCHAI- WOLF, WALAIRAT, POWERS, PATRICIA, CONRAD, RICHARD, BROWN, DAVID,... LABOURIER, EMMANUEL. (2005). An optimized isolation and labeling platform for accurate microRNA expression profiling. Copyright 2005 by RNA Society.