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

被引:25
作者
Honorato-Mauer, Jessica [1 ,2 ]
Xavier, Gabriela [1 ,2 ]
Ota, Vanessa Kiyomi [1 ,2 ]
Chehimi, Samar Nasser [3 ]
Mafra, Fernanda [3 ]
Cuoco, Cassia [1 ,2 ]
Ito, Lucas Toshio [2 ]
Ormond, Rafaella [1 ,2 ]
Asprino, Paula Fontes [4 ]
Oliveira, Adrielle [2 ,5 ]
Bugiga, Amanda Victoria Gomes [1 ,2 ]
Torrecilhas, Ana Claudia [6 ]
Bressan, Rodrigo [2 ]
Manfro, Gisele Gus [7 ,8 ]
Miguel, Euripedes Constantino [9 ]
Rohde, Luis Augusto [8 ,10 ,11 ]
Pan, Pedro Mario [5 ]
Salum, Giovanni Abrahao [8 ,12 ]
Pellegrino, Renata [3 ,13 ]
Belangero, Sintia [1 ,2 ,5 ]
Santoro, Marcos Leite [2 ]
机构
[1] Univ Fed Sao Paulo UNIFESP, Dept Morfol & Genet, Disciplina Genet, Sao Paulo, Brazil
[2] Lab Neurociencias Integrat LiNC UNIFESP, Sao Paulo, Brazil
[3] Childrens Hosp Philadelphia CHOP, Ctr Appl Genom, Philadelphia, PA USA
[4] Hosp Sirio Libanes, Sao Paulo, Brazil
[5] Univ Fed Sao Paulo UNIFESP, Dept Psiquiatria, Sao Paulo, Brazil
[6] Univ Fed Sao Paulo UNIFESP, Dept Ciencias Farmaceut, Lab Imunol Celular & Bioquim Fungos & Protozoarios, Diadema, Brazil
[7] Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Dept Psiquiatria, Porto Alegre, RS, Brazil
[8] CNPq, Natl Inst Dev Psychiat, Sao Paulo, Brazil
[9] Fac Med USP FMUSP, Inst Psiquiatria HCFMUSP, Dept Psiquiatria, Sao Paulo, Brazil
[10] Univ Fed Sao Paulo UNIFESP, Hosp Clin Porto Alegre, Disciplina Biol Mol, Porto Alegre, RS, Brazil
[11] Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Dev Psychiat Program, Porto Alegre, RS, Brazil
[12] Child Mind Inst, New York, NY USA
[13] Univ Penn, Perelman Sch Med, Philadelphia, PA USA
基金
巴西圣保罗研究基金会; 瑞典研究理事会;
关键词
PSYCHIATRIC-DISORDERS; MICROVESICLES; MECHANISM; PROTEINS; EXOSOMES; SUPPORT; CATENIN; COMPLEX; RNA;
D O I
10.1038/s41398-023-02326-4
中图分类号
R749 [精神病学];
学科分类号
100205 ;
摘要
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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页数:9
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