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Identifying biomarkers for mental health disorders using easily accessible tissues such as blood is an important area of interest for researchers working in psychiatric genetics. A group of scientists from the Federal University of São Paulo (UNIFESP) have explored this possibility by analyzing microRNAs in extracellular vesicles (EVs), which was highlighted in their recent publication in Translational Psychiatry.
EVs are lipid-bound structures secreted by cells into the extracellular space. They are produced by most cells in the body, including those important for understanding mental health disorders, like neurons and cells throughout the nervous system. One of the main types of EVs is exosomes, the smallest type of EV, which can also cross the blood-brain barrier. Detected in EVs and previously associated with a number of mental health disorders, microRNAs (miRNA) have been considered a potential opportunity for diagnosing these different disorders.
“More work has to be done to validate these miRNAs, but our findings suggest genetic material from EVs can be identified non-invasively,” said the first author of the publication, Jessica Honorato Mauer. “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.”
Details and key findings
The data evaluated in the publication was part of a larger study of psychiatric disorders in childhood (known as BHRCS, for Brazilian High-Risk Cohort Study), in which 116 individuals participated by giving two sets of blood samples during time points spaced three years apart. From the blood samples, the researchers extracted and characterized the isolated EVs. Then the miRNA from the EVs were sequenced and analyzed for variations that occurred over the time points and to identify potential associations with different psychiatric disorders.
The participants in the study were divided into four groups according to their disorder diagnosis and trajectory. Those four groups were: a control group of individuals without a diagnosis at either time point, an “incidence” group of individuals who had no diagnosis at the first time point and then later received a diagnosis, a “remission” group that received an initial diagnosis, and a “persistence” group that received a diagnosis at both points.
During the initial analysis of miRNAs, there were no statistically significant differences between each group. However, the researchers expect the results to assist future meta-analysis investigations.
Another evaluation of the study focused on associations between specific miRNAs and mental health disorders at the same time point by comparing individuals diagnosed with specific disorders versus those without any diagnosis. They found that expression of miR-328 was upregulated in children diagnosed with ADHD compared to those children without the disorder. While investigating the second time point, they associated several miRNAs with depression and anxiety. Of those associations, three miRNAs (miR-432-5p, miR-151a-5p, and miR-584-5p) were found to be downregulated in individuals with anxiety, and five (miR-4433b-5p, miR-584-5p, miR-625-3p, miR-432-5p, and miR-409-3p) were downregulated in individuals with depression.
“We know there are no biomarkers for psychiatric disorders of the kind there are for certain diseases, such as cancer,” said Dr. Marcos Leite Santoro, leader of the study and professor of Molecular Biology at UNIFESP. “I believe it will be possible in the future to produce integrated predictions based on DNA, exosome miRNAs, and interaction with the environment. In this case, for example, we’ll be able to assess a person’s genetic risk – the risk they were born with – and also evaluate the person over time by verifying changes in miRNAs or environmental exposures, so that treatment or interventions of other kinds can prevent the disease from becoming established in people who begin to present with changes in expression of this or that miRNA.”
Future directions
The next steps for the researchers are to confirm these results in other cohort life stages and expand the study to evaluate additional data generated on the original participants as adults, and additionally their children. Furthermore, they plan to analyze other data types, including genomics, transcriptomics, and epigenetics, from individuals to obtain a broader understanding of these psychiatric disorders. Environmental factors will also be incorporated into the analysis to perform a comprehensive investigation
EVs are lipid-bound structures secreted by cells into the extracellular space. They are produced by most cells in the body, including those important for understanding mental health disorders, like neurons and cells throughout the nervous system. One of the main types of EVs is exosomes, the smallest type of EV, which can also cross the blood-brain barrier. Detected in EVs and previously associated with a number of mental health disorders, microRNAs (miRNA) have been considered a potential opportunity for diagnosing these different disorders.
“More work has to be done to validate these miRNAs, but our findings suggest genetic material from EVs can be identified non-invasively,” said the first author of the publication, Jessica Honorato Mauer. “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.”
Details and key findings
The data evaluated in the publication was part of a larger study of psychiatric disorders in childhood (known as BHRCS, for Brazilian High-Risk Cohort Study), in which 116 individuals participated by giving two sets of blood samples during time points spaced three years apart. From the blood samples, the researchers extracted and characterized the isolated EVs. Then the miRNA from the EVs were sequenced and analyzed for variations that occurred over the time points and to identify potential associations with different psychiatric disorders.
The participants in the study were divided into four groups according to their disorder diagnosis and trajectory. Those four groups were: a control group of individuals without a diagnosis at either time point, an “incidence” group of individuals who had no diagnosis at the first time point and then later received a diagnosis, a “remission” group that received an initial diagnosis, and a “persistence” group that received a diagnosis at both points.
During the initial analysis of miRNAs, there were no statistically significant differences between each group. However, the researchers expect the results to assist future meta-analysis investigations.
Another evaluation of the study focused on associations between specific miRNAs and mental health disorders at the same time point by comparing individuals diagnosed with specific disorders versus those without any diagnosis. They found that expression of miR-328 was upregulated in children diagnosed with ADHD compared to those children without the disorder. While investigating the second time point, they associated several miRNAs with depression and anxiety. Of those associations, three miRNAs (miR-432-5p, miR-151a-5p, and miR-584-5p) were found to be downregulated in individuals with anxiety, and five (miR-4433b-5p, miR-584-5p, miR-625-3p, miR-432-5p, and miR-409-3p) were downregulated in individuals with depression.
“We know there are no biomarkers for psychiatric disorders of the kind there are for certain diseases, such as cancer,” said Dr. Marcos Leite Santoro, leader of the study and professor of Molecular Biology at UNIFESP. “I believe it will be possible in the future to produce integrated predictions based on DNA, exosome miRNAs, and interaction with the environment. In this case, for example, we’ll be able to assess a person’s genetic risk – the risk they were born with – and also evaluate the person over time by verifying changes in miRNAs or environmental exposures, so that treatment or interventions of other kinds can prevent the disease from becoming established in people who begin to present with changes in expression of this or that miRNA.”
Future directions
The next steps for the researchers are to confirm these results in other cohort life stages and expand the study to evaluate additional data generated on the original participants as adults, and additionally their children. Furthermore, they plan to analyze other data types, including genomics, transcriptomics, and epigenetics, from individuals to obtain a broader understanding of these psychiatric disorders. Environmental factors will also be incorporated into the analysis to perform a comprehensive investigation