Executive functions in school-aged children exposed to airborne manganese: A multilevel analysis.

Neuropsychological alterations have been identified in populations heavily exposed to metals with neurotoxic potential, such as manganese (Mn). This study examined the associations between Mn environmental exposure in school-aged children and executive functions, using structural equation modeling. Children, aged between 7 and 12 years (N = 181), were recruited from four elementary schools located in a region that is under the influence of atmospheric emissions from a ferro-manganese alloy plant in the municipality of Simões Filho, Bahia, Brazil. The following cognitive functions were evaluated: Intelligence, Inhibitory Control, Cognitive Flexibility, Verbal and Design Fluency, Verbal and Visual Working Memory and Attention. We performed structural equation modeling to identify the following executive functions latent variables: working memory, inhibitory control and cognitive flexibility. We further analyzed the relations between executive functions and Mn measured in hair (MnH) and toenails (MnTn) with linear mixed models, after controlling for co-variables. A positive effect at the individual level on working memory, inhibition control and cognitive flexibility was observed with MnTn after controlling for co-variables, but no association was found with MnH levels. However, children attending school most environmentally exposed to Mn emissions, which had the highest rate of Mn dust deposition, had the poorest scores on working memory. These findings suggest both benefits and risk of Mn on children's cognitive development.

Maternal Prenatal Anxiety and the Fetal Origins of Epigenetic Aging.

BACKGROUND: The fetal origins of mental health is a well-established framework that currently lacks a robust index of the biological embedding of prenatal adversity. The Pediatric-Buccal-Epigenetic (PedBE) clock is a novel epigenetic tool that associates with aspects of the prenatal environment, but additional validation in longitudinal datasets is required. Likewise, the relationship between prenatal maternal mental health and the PedBE clock has not been described. METHODS: Longitudinal cohorts from the Netherlands (Basal Influences on Baby Development [BIBO] n = 165) and Singapore (Growing Up in Singapore Towards Healthy Outcomes [GUSTO] n = 340) provided data on prenatal maternal anxiety and longitudinal assessments of buccal cell-derived genome-wide DNA methylation assessed at 6 and 10 years of age in BIBO, and at 3, 9, and 48 months of age in GUSTO. Measures of epigenetic age acceleration were calculated using the PedBE clock and benchmarked against an established multi-tissue epigenetic predictor. RESULTS: Prenatal maternal anxiety predicted child PedBE epigenetic age acceleration in both cohorts, with effects largely restricted to males and not females. These results were independent of obstetric, socioeconomic, and genetic risk factors, with a larger effect size for prenatal anxiety than depression. PedBE age acceleration predicted increased externalizing symptoms in males from mid- to late childhood in the BIBO cohort only. CONCLUSIONS: These findings point to the fetal origins of epigenetic age acceleration and reveal an increased sensitivity in males. Convergent evidence underscores the societal importance of providing timely and effective mental health support to pregnant individuals, which may have lasting consequences for both mother and child.

Prefrontal cortex VAMP1 gene network moderates the effect of the early environment on cognitive flexibility in children.

During development, genetic and environmental factors interact to modify specific phenotypes. Both in humans and in animal models, early adversities influence cognitive flexibility, an important brain function related to behavioral adaptation to variations in the environment. Abnormalities in cognitive functions are related to changes in synaptic connectivity in the prefrontal cortex (PFC), and altered levels of synaptic proteins. We investigated if individual variations in the expression of a network of genes co-expressed with the synaptic protein VAMP1 in the prefrontal cortex moderate the effect of early environmental quality on the performance of children in cognitive flexibility tasks. Genes overexpressed in early childhood and co-expressed with the VAMP1 gene in the PFC were selected for study. SNPs from these genes (post-clumping) were compiled in an expression-based polygenic score (PFC-ePRS-VAMP1). We evaluated cognitive performance of the 4 years-old children in two cohorts using similar cognitive flexibility tasks. In the first cohort (MAVAN) we utilized two CANTAB tasks: (a) the Intra-/Extra-dimensional Set Shift (IED) task, and (b) the Spatial Working Memory (SWM) task. In the second cohort, GUSTO, we used the Dimensional Change Card Sort (DCCS) task. The results show that in 4 years-old children, the PFC-ePRS-VAMP1 network moderates responsiveness to the effects of early adversities on the performance in attentional flexibility tests. The same result was observed for a spatial working memory task. Compared to attentional flexibility, reversal learning showed opposite effects of the environment, as moderated by the ePRS. A parallel ICA analysis was performed to identify relationships between whole-brain voxel based gray matter density and SNPs that comprise the PFC-ePRS-VAMP1. The early environment predicts differences in gray matter content in regions such as prefrontal and temporal cortices, significantly associated with a genetic component related to Wnt signaling pathways. Our data suggest that a network of genes co-expressed with VAMP1 in the PFC moderates the influence of early environment on cognitive function in children.

Policy Implications of Achievement Testing Using Multilevel Models: The Case of Brazilian Elementary Schools.

Large-scale educational assessment has been established as source of descriptive, evaluative and interpretative information that influence educational policies worldwide throughout the last third of the twentieth century. In the 1990s the Brazilian Ministry of Education developed the National Basic Education Assessment System (SAEB) that regularly measures management, resource and contextual school features and academic achievement in public and private institutions. In 2005, after significant piloting and review of the SAEB, a new sampling strategy was taken and Prova Brasil became the new instrument used by the Ministry to assess skills in Portuguese (reading comprehension) and Mathematics (problem solving), as well as collecting contextual information concerning the school, principal, teacher, and the students. This study aims to identify which variables are predictors of academic achievement of fifth grade students on Prova Brasil. Across a large sample of students, multilevel models tested a large number of variables relevant to student achievement. This approach uncovered critical variables not commonly seen as significant in light of other achievement determinants, including student habits, teacher ethnicity, and school technological resources. As such, this approach demonstrates the value of MLM to appropriately nuanced educational policies that reflect critical influences on student achievement. Its implications for wider application for psychology studies that may have relevant impacts for policy are also discussed.