| Full text | |
| Author(s): Show less - |
Spindola, Leticia M.
;
Santoro, Marcos L.
;
Pan, Pedro M.
;
Ota, Vanessa K.
;
Xavier, Gabriela
;
Carvalho, Carolina M.
;
Talarico, Fernanda
;
Sleiman, Patrick
;
March, Michael
;
Pellegrino, Renata
;
Brietzke, Elisa
;
Grassi-Oliveira, Rodrigo
;
Mari, Jair J.
;
Gadelha, Ary
;
Miguel, Euripedes C.
;
Rohde, Luis A.
;
Bressan, Rodrigo A.
;
Mazzotti, Diego R.
;
Sato, Joao R.
;
Salum, Giovanni A.
;
Hakonarson, Hakon
;
Belangero, Sintia, I
Total Authors: 22
|
| Document type: | Journal article |
| Source: | CLINICAL EPIGENETICS; v. 11, n. 1, p. 16-pg., 2019-10-21. |
| Abstract | |
Background Psychiatric symptomatology during late childhood and early adolescence tends to persist later in life. In the present longitudinal study, we aimed to identify changes in genome-wide DNA methylation patterns that were associated with the emergence of psychopathology in youths from the Brazilian High-Risk Cohort (HRC) for psychiatric disorders. Moreover, for the differentially methylated genes, we verified whether differences in DNA methylation corresponded to differences in mRNA transcript levels by analyzing the gene expression levels in the blood and by correlating the variation of DNA methylation values with the variation of mRNA levels of the same individuals. Finally, we examined whether the variations in DNA methylation and mRNA levels were correlated with psychopathology measurements over time. Methods We selected 24 youths from the HRC who presented with an increase in dimensional psychopathology at a 3-year follow-up as measured by the Child Behavior Checklist (CBCL). The DNA methylation and gene expression data were compared in peripheral blood samples (n = 48) obtained from the 24 youths before and after developing psychopathology. We implemented a methodological framework to reduce the effect of chronological age on DNA methylation using an independent population of 140 youths and the effect of puberty using data from the literature. Results We identified 663 differentially methylated positions (DMPs) and 90 differentially methylated regions (DMRs) associated with the emergence of psychopathology. We observed that 15 DMPs were mapped to genes that were differentially expressed in the blood; among these, we found a correlation between the DNA methylation and mRNA levels of RB1CC1 and a correlation between the CBCL and mRNA levels of KMT2E. Of the DMRs, three genes were differentially expressed: ASCL2, which is involved in neurogenesis; HLA-E, which is mapped to the MHC loci; and RPS6KB1, the gene expression of which was correlated with an increase in the CBCL between the time points. Conclusions We observed that changes in DNA methylation and, consequently, in gene expression in the peripheral blood occurred concurrently with the emergence of dimensional psychopathology in youths. Therefore, epigenomic modulations might be involved in the regulation of an individual's development of psychopathology. (AU) | |
| FAPESP's process: | 15/10733-0 - Analysis of DNA methylation in blood associated with emergence of psychiatric symptoms and environmental stressors in adolescence |
| Grantee: | Leticia Maria Nery Spindola |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 17/05339-7 - Characterization of gene expression profiles in children and adolescents at risk for mental disorders |
| Grantee: | Vanessa Kiyomi Ota Kuniyoshi |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 16/04983-7 - Neuroimaging, genomics, transcriptomics and epigenomics: dealing with big data toward an integrative model of mental disorders |
| Grantee: | Jair de Jesus Mari |
| Support Opportunities: | Research Grants - eScience and Data Science Program - Regular Program Grants |
| FAPESP's process: | 14/50917-0 - INCT 2014: developmental psychiatry for children and adolescents |
| Grantee: | Eurípedes Constantino Miguel Filho |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 14/07280-1 - Search for genetic markers of risk, progression and response to treatment |
| Grantee: | Síntia Iole Nogueira Belangero |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 16/25374-9 - Methylomic changes during development of psychiatric disorders |
| Grantee: | Leticia Maria Nery Spindola |
| Support Opportunities: | Scholarships abroad - Research Internship - Doctorate |