Fig. 1

Overview of the study design. We selected 24 youths from the Brazilian High-Risk Cohort (HRC) for psychiatric disorders who presented with an increase in dimensional psychopathology after 3 years of follow-up as measured by the Child Behavior Checklist (CBCL). After implementing a methodological framework to reduce the effect of important confounders (chronological age and puberty) on the results, genome-wide DNA methylation was investigated in the context of both differentially methylated positions (DMPs) and differentially methylated regions (DMRs). Moreover, for differentially methylated genes, we verified whether differences in DNA methylation corresponded to differences in mRNA transcripts by analyzing gene expression levels in the blood from the same individuals. Finally, we examined whether there were correlations between (a) the variation in DNA methylation (ΔDNAm) and the variation in gene expression (ΔmRNA); (b) the variation in the total score of the CBCL (ΔCBCL) and ΔDNAm; and (c) ΔCBCL and ΔmRNA. The variations were calculated by subtracting wave 1 (W1) values from wave 0 (W0) values