Associations between telomere length, glucocorticoid receptor gene DNA methylation, volume of stress-related brain structures, and academic performance in middle-school-age children.

Background: The biological embedding theory posits that early life experiences can lead to enduring physiological and molecular changes impacting various life outcomes, notably academic performance. Studying previously revealed and objective biomarkers of early life stress exposure, such as telomere length (TL), glucocorticoid receptor gene DNA methylation (DNAme), and the volume of brain structures involved in the regulation of HPA axis functioning (the hippocampus, the amygdala, and the medial prefrontal cortex), in relation to academic performance is crucial. This approach provides an objective measure that surpasses the limitations of self-reported early life adversity and reveals potential molecular and neurological targets for interventions to enhance academic outcomes. Methods: The participants were 52 children of Mexican or Central American origin aged 11.6-15.6 years. DNA methylation levels and TL were analyzed in three cell sources: saliva, whole blood, and T cells derived from whole blood. Results: Overall, the concordance across three systems of stress-related biomarkers (TL, DNAme, and the brain) was observed to some extent, although it was less pronounced than we expected; no consistency in different cell sources was revealed. Each of the academic domains that we studied was characterized by a unique and distinct complex of associations with biomarkers, both in terms of the type of biomarker, the directionality of the observed effects, and the cell source of biomarkers. Furthermore, there were biomarker-by-sex interaction effects in predicting academic performance measures. Conclusions: Assessed in an understudied youth sample, these preliminary data present new essential evidence for a deepened understanding of the biological mechanisms behind associations between exposure to early life stress and academic performance.

Neuroendocrine and autonomic stress systems activity in young adults raised by mothers with mental health and substance abuse problems: A prospective cohort study.

Among the well-known physiological consequences of early adverse environments is dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. A number of studies demonstrate that negative parenting and living with parents with a history of substance abuse and mental health problems may be associated with HPA axis dysregulation in children. In contrast, studies of more delayed effects in adult offspring, especially prospective, are still scarce. This study was a prospective longitudinal investigation of the association between maternal mental illnesses/substance abuse and maternal negative parenting/parental stress on one side and, on the other side, adult offspring outcomes 10 years later-specifically, we studied the activity of offspring's neuroendocrine (cortisol) and autonomic (heart rate) systems when exposed to a mild psychological stressor. Children of mothers with mental illnesses and/or substance abuse were exposed to more disadvantaged conditions (higher negative parenting and community violence). Despite this, maternal risk groups (having a mother with mental illnesses and/or substance abuse) were not associated with any of the indicators of stress systems activity. Regardless of the risk group, participants with dysregulated HPA axis activity experienced a higher level of negative parenting. Altogether, our study provides evidence that negative parenting may have long-lasting effects on stress-sensitive physiological mechanisms.

Stress in the onset and aggravation of learning disabilities.

Despite substantial grounds for such research, the role of chronic exposure to stressors in the onset and aggravation of learning disabilities (LDs) is largely unexplored. In this review, we first consider the hormonal, (epi)genetic, and neurobiological mechanisms that might underlie the impact of adverse childhood experiences, a form of chronic stressors, on the onset of LDs. We then found that stress factors combined with feelings of inferiority, low self-esteem, and peer victimization could potentially further aggravate academic failures in children with LDs. Since effective evidence-based interventions for reducing chronic stress in children with LDs could improve their academic performance, consideration of the role of exposure to stressors in children with LDs has both theoretical and practical importance, especially when delivered in combination with academic interventions.

Epigenetic regulation of cognition: A circumscribed review of the field.

The last decade has been marked by an increased interest in relating epigenetic mechanisms to complex human behaviors, although this interest has not been balanced, accentuating various types of affective and primarily ignoring cognitive functioning. Recent animal model data support the view that epigenetic processes play a role in learning and memory consolidation and help transmit acquired memories even across generations. In this review, we provide an overview of various types of epigenetic mechanisms in the brain (DNA methylation, histone modification, and noncoding RNA action) and discuss their impact proximally on gene transcription, protein synthesis, and synaptic plasticity and distally on learning, memory, and other cognitive functions. Of particular importance are observations that neuronal activation regulates the dynamics of the epigenome's functioning under precise timing, with subsequent alterations in the gene expression profile. In turn, epigenetic regulation impacts neuronal action, closing the circle and substantiating the signaling pathways that underlie, at least partially, learning, memory, and other cognitive processes.

Epigenetic Patterns Modulate the Connection Between Developmental Dynamics of Parenting and Offspring Psychosocial Adjustment.

This study attempted to establish and quantify the connections between parenting, offspring psychosocial adjustment, and the epigenome. The participants, 35 African American young adults (19 females and 16 males; age = 17-29.5 years), represented a subsample of a 3-wave longitudinal 15-year study on the developmental trajectories of low-income urban mother-offspring dyads. Mothers were assessed on their perceptions of maternal stress at each wave. Offspring were assessed on their perceptions of maternal parenting at each wave and on their adaptive and maladaptive behavior at the last wave. Genome-wide DNA methylation in peripheral T lymphocytes at the third wave was assayed using Methyl Binding Domain(MBD) sequencing. Statistically significant associations were identified between the change in offspring's perception of parenting from middle childhood to adulthood and the DNA methylation in offspring's adult genomes. Specifically, the slope of perceived parental rejection across the 3 time points was related to an increase in methylation, or a potential downregulation, of 565 genes thought to be involved in the control of a broad spectrum of biological functions generally related to cellular signaling. A subset of these epigenetic marks, clustered in 23 genes, some of which participate in the development and functioning of the CNS, were in turn associated with psychosocial adjustment as captured by interpersonal relationships and emotional self-evaluation. This appears to be one of the first investigations of the modulating role of the methylome in associations between developmental dynamics of parenting throughout the formative years of child and adolescent development and psychosocial adjustment in adulthood.

Comparison of whole-genome DNA methylation patterns in whole blood, saliva, and lymphoblastoid cell lines.

Epigenetic mechanisms, including DNA methylation, that underlie neuropsychiatric conditions have become a promising area of research. Most commonly used DNA sources in such studies are peripheral (whole) blood (WB), saliva (SL), and lymphoblastoid cell lines (LCLs); thus, the question of the consistency of DNA methylation patterns in those cells is of particular interest. To investigate this question we performed comparative analyses of methylation patterns in WB, SL, and LCLs derived from the same individuals, using Illumina HumanMethylation27 BeadChip arrays. Our results showed that DNA methylation patterns in SL are relatively consistent with those in WB, whereas the patterns in LCLs are similarly distinct from both WB and SL. The results indicated that due to multiple random and directed changes in DNA methylation throughout cell culturing, LCLs are not a reliable source of DNA for epigenetic studies and should be used with caution when investigating epigenetic mechanisms underlying biological processes.

Gene expression in the human brain: the current state of the study of specificity and spatiotemporal dynamics.

Gene expression is one of the main molecular processes regulating the differentiation, development, and functioning of cells and tissues. In this review a handful of relevant terms and concepts are introduced and the most common techniques used in studies of gene expression/expression profiling (also referred to as studies of the transcriptome or transcriptomics) are described. The main foci of this review are the advancements in studies of the transcriptome in the human brain, the transcriptome's variability across different brain structures, and the systematic changes that occur through different developmental stages across the life span in general and childhood in particular. Finally, the question of how the accumulating data on the spatial and temporal dynamics of the transcriptome may shed light on the molecular mechanisms of the typical and atypical development of the central nervous system is addressed.

Age-related changes of gene expression in the neocortex: preliminary data on RNA-Seq of the transcriptome in three functionally distinct cortical areas.

The study of gene expression (i.e., the study of the transcriptome) in different cells and tissues allows us to understand the molecular mechanisms of their differentiation, development and functioning. In this article, we describe some studies of gene-expression profiling for the purposes of understanding developmental (age-related) changes in the brain using different technologies (e.g., DNA-Microarray) and the new and increasingly popular RNA-Seq. We focus on advancements in studies of gene expression in the human brain, which have provided data on the structure and age-related variability of the transcriptome in the brain. We present data on RNA-Seq of the transcriptome in three distinct areas of the neocortex from different ages: mature and elderly individuals. We report that most age-related transcriptional changes affect cellular signaling systems, and, as a result, the transmission of nerve impulses. In general, the results demonstrate the high potential of RNA-Seq for the study of distinctive features of gene expression among cortical areas and the changes in expression through normal and atypical development of the central nervous system.

Differential patterns of whole-genome DNA methylation in institutionalized children and children raised by their biological parents.

Previous studies with nonhuman species have shown that animals exposed to early adversity show differential DNA methylation relative to comparison animals. The current study examined differential methylation among 14 children raised since birth in institutional care and 14 comparison children raised by their biological parents. Blood samples were taken from children in middle childhood. Analysis of whole-genome methylation patterns was performed using the Infinium HumanMethylation27 BeadChip assay (Illumina), which contains 27,578 CpG sites, covering approximately 14,000 gene promoters. Group differences were registered, which were characterized primarily by greater methylation in the institutionalized group relative to the comparison group, with most of these differences in genes involved in the control of immune response and cellular signaling systems, including a number of crucial players important for neural communication and brain development and functioning. The findings suggest that patterns of differential methylation seen in nonhuman species with altered maternal care are also characteristic of children who experience early maternal separation.