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 Using real-time quantitative PCR, we compared the expression of 435 miRNAs and 18 snoRNAs in post-mortem 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 post-mortem interval were found to affect the greatest proportion of miRNAs. 19% of miRNAs analyzed 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 under-expression of several miRNAs may be involved in the complex pathogenesis of major psychosis.

microRNA and mRNA profiles in nucleus accumbens underlying depression versus resilience in response to chronic stress

“…If major depression is due to lack of reward, the analysis of molecular profiles in the nucleus accumbens from CUMS‐induced depression and resilience should help to figure out the role of the nucleus accumbens in major depression and resilience based on molecules analyzed. The alternations of certain genes have not been observed in previous analyses (Bai et al, 2014; Elizalde et al, 2010; Li et al, 2013; Liu et al, 2015; Moreau, Bruse, David‐Rus, Buyske, & Brzustowicz, 2011; Rajkowska et al, 2015; Smalheiser et al, 2012, 2011, 2014), including Cckar , Tshr , Kcnj5 , Alox12 , Slc17a6 , Per2 , Rtn4r , and Nrn1 . These genes in the nucleus accumbens may be newly working for major depression or resilience.…”

Deficiency of Dgcr8 , a gene disrupted by the 22q11.2 microdeletion, results in altered short-term plasticity in the prefrontal cortex

“…Emerging evidence suggests a strong association between miRNAdependent dysregulation of gene expression and susceptibility to psychiatric disorders, such as SCZ (3,31,32). In particular, previous work has shown that impaired miRNA formation (caused by Dgcr8 deficiency) is one of the genetic factors contributing to the behavioral and neuronal phenotypes associated with 22q11.2 deletions, a well-established SCZ predisposing mutation.…”

Detection of Circulating miRNA Levels in Schizophrenia

“…It has been suggested that 70% of known miRNAs are expressed in the CNS, some of which are brain specific or brain-region specific (7), implying that these miRNAs may play a vital role in the development of diseases in the CNS (8). Altered miRNA levels have been found in CSF and postmortem brain of schizophrenia patients (9,10), but no ideal miRNAs have been identified in the circulation that might be used as biomarkers for clinical applications. As plasma and serum samples can be easily collected, it is important to detect circulating miRNAs of interest as diagnostic biomarkers, as opposed to potential biomarkers in other tissues.…”