According to a collaborative study by researchers at National Taiwan University and University of Melbourne, aberrant expression of microRNAs (miRNAs), which are master regulators of essential cellular processes, in peripheral blood of patients with schizophrenia were not affected by the hospitalization of two months. Although the aberrant expressions seen in the peripheral blood of two candidate miRNAs (hsa-miR-34a and hsa-miR-548d) were not replicated in the post mortem brain tissue, age-dependent increases were found in hsa-miR-34a expressions in human cortical region but not in subcortical region. This study has been published online 19 January in Translational Psychiatry.
[Photo: Dr. Chi-Yu Lai]
The study was conducted by Dr. Chi-Yu Lai, a former doctoral student at Taiwan and a visiting postdoctoral fellow at University of Melbourne, and her thesis advisors Drs. Wei J. Chen & Hai-Gwo Hwu, as well as collaborators Drs. Elizabeth Scarr and Brian Dean at University of Melbourne, among others. The peripheral blood sample was provided by the Taiwan team, and the post mortem brain sample was provided by the University of Melbourne team.
As pointed out by Dr. Wei J. Chen, corresponding author and the leader of the Taiwan team, profiling of miRNA is increasingly being undertaken in the search for biomarkers in a variety of diseases. His research team previously identified a 7-miRNA signature of altered expression levels in peripheral blood mononuclear cells (PBMC) from people with schizophrenia.
“To our knowledge, this is the first study to examine the expression changes in seven candidate miRNAs in the PBMC of people with schizophrenia at different clinical time points,” said Dr. Chi-Yu Lai, first author and currently a visiting scholar in Salk Institute at La Jolla, CA, “and also the first to investigate whether the aberrant expression in the PBMC of two selected miRNAs could be replicated in the postmortem brain from an independent sample of people with schizophrenia.”
The results revealed that the expressions of the seven miRNAs in PBMC were not affected by the hospitalization of two months, which resulted in significant improvement of clinical symptoms. The aberrant expressions seen in the PBMC of two candidate miRNAs (hsa-miR-34a and hsa-miR-548d) were not replicated in the brain samples. However, the authors find age-dependent increases in hsa-miR-34a expressions in human cortical region (i.e., BA46) but not in subcortical region. Furthermore, the correlation between hsa-miR-34a expression level in BA46 and age is much stronger in the controls than in the cases, and the corresponding correlation in PBMCs is only seen in the cases.
Dr. Brian Dean, the leader of the University of Melbourne team, said: “Whilst the changes in expression of hsa-miR-34a and hsa-miR-548d seen in the periphery were not present in the two brain regions examined in this study, this does not negate the possibility that the expression changes in miRNAs in the PBMC could be clinically useful biomarkers for schizophrenia.”
The authors conclude that the association between the miRNA dysregulations, the disease predisposition and aging warrants further investigation. Taken together, this study provides further insight on the candidate peripheral miRNAs as stable biomarkers for the diagnostics of schizophrenia.