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Alterations in microRNA of extracellular vesicles associated with major depression, attention-deficit/hyperactivity and anxiety disorders in adolescents

Extracellular vesicles (EVs) are present in numerous peripheral bodily fluids and function in critical biological processes, including cell-to-cell communication. Most relevant to the present study, EVs contain microRNAs (miRNAs), and initial evidence from the field indicates that miRNAs detected in...

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Autores principales: Honorato-Mauer, Jessica, Xavier, Gabriela, Ota, Vanessa Kiyomi, Chehimi, Samar Nasser, Mafra, Fernanda, Cuóco, Cássia, Ito, Lucas Toshio, Ormond, Rafaella, Asprino, Paula Fontes, Oliveira, Adrielle, Bugiga, Amanda Victoria Gomes, Torrecilhas, Ana Claudia, Bressan, Rodrigo, Manfro, Gisele Gus, Miguel, Euripedes Constantino, Rohde, Luis Augusto, Pan, Pedro Mario, Salum, Giovanni Abrahão, Pellegrino, Renata, Belangero, Sintia, Santoro, Marcos Leite
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9902559/
https://www.ncbi.nlm.nih.gov/pubmed/36746925
http://dx.doi.org/10.1038/s41398-023-02326-4
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author Honorato-Mauer, Jessica
Xavier, Gabriela
Ota, Vanessa Kiyomi
Chehimi, Samar Nasser
Mafra, Fernanda
Cuóco, Cássia
Ito, Lucas Toshio
Ormond, Rafaella
Asprino, Paula Fontes
Oliveira, Adrielle
Bugiga, Amanda Victoria Gomes
Torrecilhas, Ana Claudia
Bressan, Rodrigo
Manfro, Gisele Gus
Miguel, Euripedes Constantino
Rohde, Luis Augusto
Pan, Pedro Mario
Salum, Giovanni Abrahão
Pellegrino, Renata
Belangero, Sintia
Santoro, Marcos Leite
author_facet Honorato-Mauer, Jessica
Xavier, Gabriela
Ota, Vanessa Kiyomi
Chehimi, Samar Nasser
Mafra, Fernanda
Cuóco, Cássia
Ito, Lucas Toshio
Ormond, Rafaella
Asprino, Paula Fontes
Oliveira, Adrielle
Bugiga, Amanda Victoria Gomes
Torrecilhas, Ana Claudia
Bressan, Rodrigo
Manfro, Gisele Gus
Miguel, Euripedes Constantino
Rohde, Luis Augusto
Pan, Pedro Mario
Salum, Giovanni Abrahão
Pellegrino, Renata
Belangero, Sintia
Santoro, Marcos Leite
author_sort Honorato-Mauer, Jessica
collection PubMed
description Extracellular vesicles (EVs) are present in numerous peripheral bodily fluids and function in critical biological processes, including cell-to-cell communication. Most relevant to the present study, EVs contain microRNAs (miRNAs), and initial evidence from the field indicates that miRNAs detected in circulating EVs have been previously associated with mental health disorders. Here, we conducted an exploratory longitudinal and cross-sectional analysis of miRNA expression in serum EVs from adolescent participants. We analyzed data from a larger ongoing cohort study, evaluating 116 adolescent participants at two time points (wave 1 and wave 2) separated by three years. Two separate data analyses were employed: A cross-sectional analysis compared individuals diagnosed with Major Depressive Disorder (MDD), Anxiety disorders (ANX) and Attention deficit/Hyperactivity disorder (ADHD) with individuals without psychiatric diagnosis at each time point. A longitudinal analysis assessed changes in miRNA expression over time between four groups showing different diagnostic trajectories (persistent diagnosis, first incidence, remitted and typically developing/control). Total EVs were isolated, characterized by size distribution and membrane proteins, and miRNAs were isolated and sequenced. We then selected differentially expressed miRNAs for target prediction and pathway enrichment analysis. In the longitudinal analysis, we did not observe any statistically significant results. In the cross-sectional analysis: in the ADHD group, we observed an upregulation of miR-328-3p at wave 1 only; in the MDD group, we observed a downregulation of miR-4433b-5p, miR-584-5p, miR-625-3p, miR-432-5p and miR-409-3p at wave 2 only; and in the ANX group, we observed a downregulation of miR-432-5p, miR-151a-5p and miR-584-5p in ANX cases at wave 2 only. Our results identified previously observed and novel differentially expressed miRNAs and their relationship with three mental health disorders. These data are consistent with the notion that these miRNAs might regulate the expression of genes associated with these traits in genome-wide association studies. The findings support the promise of continued identification of miRNAs contained within peripheral EVs as biomarkers for mental health disorders.
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spelling pubmed-99025592023-02-08 Alterations in microRNA of extracellular vesicles associated with major depression, attention-deficit/hyperactivity and anxiety disorders in adolescents Honorato-Mauer, Jessica Xavier, Gabriela Ota, Vanessa Kiyomi Chehimi, Samar Nasser Mafra, Fernanda Cuóco, Cássia Ito, Lucas Toshio Ormond, Rafaella Asprino, Paula Fontes Oliveira, Adrielle Bugiga, Amanda Victoria Gomes Torrecilhas, Ana Claudia Bressan, Rodrigo Manfro, Gisele Gus Miguel, Euripedes Constantino Rohde, Luis Augusto Pan, Pedro Mario Salum, Giovanni Abrahão Pellegrino, Renata Belangero, Sintia Santoro, Marcos Leite Transl Psychiatry Article Extracellular vesicles (EVs) are present in numerous peripheral bodily fluids and function in critical biological processes, including cell-to-cell communication. Most relevant to the present study, EVs contain microRNAs (miRNAs), and initial evidence from the field indicates that miRNAs detected in circulating EVs have been previously associated with mental health disorders. Here, we conducted an exploratory longitudinal and cross-sectional analysis of miRNA expression in serum EVs from adolescent participants. We analyzed data from a larger ongoing cohort study, evaluating 116 adolescent participants at two time points (wave 1 and wave 2) separated by three years. Two separate data analyses were employed: A cross-sectional analysis compared individuals diagnosed with Major Depressive Disorder (MDD), Anxiety disorders (ANX) and Attention deficit/Hyperactivity disorder (ADHD) with individuals without psychiatric diagnosis at each time point. A longitudinal analysis assessed changes in miRNA expression over time between four groups showing different diagnostic trajectories (persistent diagnosis, first incidence, remitted and typically developing/control). Total EVs were isolated, characterized by size distribution and membrane proteins, and miRNAs were isolated and sequenced. We then selected differentially expressed miRNAs for target prediction and pathway enrichment analysis. In the longitudinal analysis, we did not observe any statistically significant results. In the cross-sectional analysis: in the ADHD group, we observed an upregulation of miR-328-3p at wave 1 only; in the MDD group, we observed a downregulation of miR-4433b-5p, miR-584-5p, miR-625-3p, miR-432-5p and miR-409-3p at wave 2 only; and in the ANX group, we observed a downregulation of miR-432-5p, miR-151a-5p and miR-584-5p in ANX cases at wave 2 only. Our results identified previously observed and novel differentially expressed miRNAs and their relationship with three mental health disorders. These data are consistent with the notion that these miRNAs might regulate the expression of genes associated with these traits in genome-wide association studies. The findings support the promise of continued identification of miRNAs contained within peripheral EVs as biomarkers for mental health disorders. Nature Publishing Group UK 2023-02-06 /pmc/articles/PMC9902559/ /pubmed/36746925 http://dx.doi.org/10.1038/s41398-023-02326-4 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Honorato-Mauer, Jessica
Xavier, Gabriela
Ota, Vanessa Kiyomi
Chehimi, Samar Nasser
Mafra, Fernanda
Cuóco, Cássia
Ito, Lucas Toshio
Ormond, Rafaella
Asprino, Paula Fontes
Oliveira, Adrielle
Bugiga, Amanda Victoria Gomes
Torrecilhas, Ana Claudia
Bressan, Rodrigo
Manfro, Gisele Gus
Miguel, Euripedes Constantino
Rohde, Luis Augusto
Pan, Pedro Mario
Salum, Giovanni Abrahão
Pellegrino, Renata
Belangero, Sintia
Santoro, Marcos Leite
Alterations in microRNA of extracellular vesicles associated with major depression, attention-deficit/hyperactivity and anxiety disorders in adolescents
title Alterations in microRNA of extracellular vesicles associated with major depression, attention-deficit/hyperactivity and anxiety disorders in adolescents
title_full Alterations in microRNA of extracellular vesicles associated with major depression, attention-deficit/hyperactivity and anxiety disorders in adolescents
title_fullStr Alterations in microRNA of extracellular vesicles associated with major depression, attention-deficit/hyperactivity and anxiety disorders in adolescents
title_full_unstemmed Alterations in microRNA of extracellular vesicles associated with major depression, attention-deficit/hyperactivity and anxiety disorders in adolescents
title_short Alterations in microRNA of extracellular vesicles associated with major depression, attention-deficit/hyperactivity and anxiety disorders in adolescents
title_sort alterations in microrna of extracellular vesicles associated with major depression, attention-deficit/hyperactivity and anxiety disorders in adolescents
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9902559/
https://www.ncbi.nlm.nih.gov/pubmed/36746925
http://dx.doi.org/10.1038/s41398-023-02326-4
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