" Differentially Methylated Genes in Saliva are linked to Childhood Stress "was posted by Ligia A. Papale, Leslie J. Seltzer, Andy Madrid, Seth D. Pollak, and Reid S. Alisch in Scientific Reports recently.
Chronic and severe stress exposure in early childhood is associated with the development of psychiatric disorders. Yet, the molecular mechanisms underlying this relationship remain poorly understood.
The authors profile molecular marks (DNA methylation and gene expression) throughout the human genome to determine the associations between childhood stress exposure and gene regulation. To do so, they collected saliva tissue from Twenty-two girls between 9 and 12 years of age (mean=10.9 years, sd – 1 year, 2 months) participated in this study. Half of the children experienced normative levels of child stress exposure (average age=11.23, SD=1.34 years) and the other half had experienced extremely high levels of stress exposure (average age=10.61, SD=1.14 years).
They found 122 differentially methylated genes (FDR P-value<0.05) associated with high childhood stress exposures that affect brain development. Of these differentially methylated genes, 12 also differed in gene expression.
As expected, children with high levels of life stress exposure were experiencing more behavioral problems (assessed via the Child Behavior Checklist), R2=0.28; P-value<0.006. The specific symptoms expressed by children are presented in Table 1.
Table 1
Summary of behavioral phenotypes in children exposed to high stress (as assessed via the Child Behavior Checklist), at the time of saliva collection.
| R2 | P-value |
Incidence of Externalizing Symptoms | 0.28 | <0.006 |
Difficulties with Social Interactions | 0.51 | <0.0001 |
General Social Competence | 0.39 | <0.001 |
Reaction to Upsetting Thoughts | 0.28 | <0.007 |
Rates of Internalizing Symptoms | 0.28 | <0.007 |
Engagement in Extracurricular Activities | −0.56 | <0.0001 |
Clinical Diagnosis of Anxiety Disorder | 0.31 | <0.004 |
Overall Problems with Behavior | 0.28 | <0.006 |
To further investigate the potential effects of stress exposure on gene regulation, They examined the DNA sequences flanking all the differentially methylated loci. This analysis revealed enrichment of known binding sites for transcription factors, suggesting that DNA methylation may regulate gene expression by mediating transcription factor binding on these genes. Together, these findings indicate a possible neuromolecular mechanism linking children’s social experiences with risk for anxiety and depressive disorders.
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