New Delhi: Researchers have analysed microRNAs in extracellular vesicles (EVs), produced by most cells in the body including neurons and other nervous system cells, and found them to be associated with mental health disorders. The study by researchers at the Federal University of Sao Paulo (UNIFESP) in Brazil is published in the journal Translational Psychiatry.
MicroRNAs (miRNAs) are small transcripts that target messenger RNAs and regulate the expression of several genes at once. They can be detected in biofluids and EVs and have been associated with mental disorders, including depression, anxiety, and attention deficit/hyperactivity disorder (ADHD), paving the way for early diagnosis and treatment in future.
Exosomes, the smallest type of EV, can cross the blood-brain barrier that protects the brain from pathogens and toxins. "More work has to be done to validate these miRNAs, but our findings suggest genetic material from EVs can be identified non-invasively," said Jessica Honorato Mauer, first author of the article.
"We can't be absolutely sure the exosomes analyzed came from the brain, but we know they regulate gene expression in several types of tissue and may be involved in mechanisms that increase the risk of mental health disorders," said Mauer. The study sample consisted of 116 participants in a study of psychiatric disorders in childhood (Brazilian High-Risk Cohort Study).
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Two sets of blood samples were collected at time points three years apart (in adolescence and early adulthood). EVs were extracted from the blood serum and characterised. The researchers then sequenced miRNAs extracted from the EVs to analyze variations over time in search of associations with specific psychiatric disorders.
As part of this longitudinal analysis, they divided the participants into four groups according to disorder diagnosis and trajectory: a control group comprising those without a diagnosis at either time point; an "incidence" group comprising those who had no diagnosis at the first time point and then transited to a diagnosis; a "remission" group with a diagnosis only initially; and a "persistence" group with a diagnosis at both points.
While the analysis of miRNAs from the four groups did not bring to light any statistically significant differences, the results of the statistical tests could be used in future meta-analysis investigations, the researchers said. The researchers' second analysis looked for associations between miRNAs and specific disorders at the same time point, comparing individuals diagnosed with depression, anxiety or ADHD versus those without any diagnosis.
Expression of miR-328 was found to be upregulated in children with ADHD compared with those without the disorder. For the second time point, miRNAs were found to be associated with depression and anxiety. Three of these (miR-432-5p, miR-151a-5p and miR-584-5p) were downregulated in subjects with anxiety, and five (miR-4433b-5p, miR-584-5p, miR-625-3p, miR-432-5p and miR-409-3p) in those with depression. "I believe it will be possible in future to produce integrated predictions based on DNA, exosome miRNAs and interaction with the environment," said Marcos Leite Santoro, a professor of molecular biology at UNIFESP and last author of the article. (PTI)
