Altered microRNA expression profiles in postmortem brain samples from individuals with schizophrenia and bipolar disorder

Abstract

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.

Figure 1. Magnitude of expression changes

Fold changes with 95% confidence intervals for miRNAs with posterior probability of non-zero effect of diagnosis exceeding 95% (black bars represent the bipolar group, gray bars represent the schizophrenia group).

Figure 2. Separately sorted effect sizes for diagnostic classes

Expression levels were standardized such that transitioning from normal to the indicated affected category shifts miRNA expression by units of standard deviation on the Y-axis. Bolder negative effects for the bipolar group are evident.