期刊
BIOLOGICAL PSYCHIATRY
卷 69, 期 2, 页码 188-193出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2010.09.039
关键词
Bayesian model averaging; bipolar disorder; DGCR8; major psychosis; microRNA; schizophrenia
资金
- National Institutes of Mental Health [R01 MH80429]
- National Alliance for Research on Schizophrenia and Depression/Staglin Family Music Festival Schizophrenia Research Award [T32 MH019957-10]
- Ruth L. Kirschstein National Research Service
- National Institute on Alcohol Abuse and Alcoholism [K25 AA015346]
Background: MicroRNAs (miRNAs) are potent regulators of gene expression with proposed roles in brain development and function. We hypothesized that miRNA expression profiles are altered in individuals with severe psychiatric disorders. Methods: With real-time quantitative polymerase chain reaction, we compared the expression of 435 miRNAs and 18 small nucleolar RNAs in postmortem brain tissue samples from individuals with schizophrenia, individuals with bipolar disorder, and psychiatrically healthy control subjects (n = 35 each group). Detailed demographic data, sample selection and storage conditions, and drug and substance exposure histories were available for all subjects. Bayesian model averaging was used to simultaneously assess the impact of these covariates as well as the psychiatric phenotype on miRNA expression profiles. Results: Of the variables considered, sample storage time, brain pH, alcohol at time of death, and postmortem interval were found to affect the greatest proportion of miRNAs. Of miRNAs analyzed, 19% exhibited positive evidence of altered expression due to a diagnosis of schizophrenia or bipolar disorder. Both conditions were associated with reduced miRNA expression levels, with a much more pronounced effect observed for bipolar disorder. Conclusions: This study suggests that modest underexpression of several miRNAs might be involved in the complex pathogenesis of major psychosis.
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