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Differenzierung genetisch- und umweltbedingter Einflüsse auf sozioökonomische Unterschiede in der Cortisolausschüttung und Exekutivfunktion bei Kindern

Antragstellerin Dr. Laurel Raffington
Fachliche Zuordnung Entwicklungspsychologie und Pädagogische Psychologie
Allgemeine, Kognitive und Mathematische Psychologie
Förderung Förderung von 2018 bis 2021
Projektkennung Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 407466711
 
Erstellungsjahr 2021

Zusammenfassung der Projektergebnisse

Children’s performance on cognitive tasks and educational performance robustly predict their future social attainments and health, and consistently differ by major dimensions of social inequality, such as education, income, and race/ethnicity. Socioeconomic and racial disparities in child cognitive development arise through various factors tied to classism and racism, including inequitable access to high-quality childcare, healthcare, nutrition, and differences in exposure to toxicants, family and neighborhood stress, among other factors. Because saliva can easily be collected in large-scale pediatric epidemiological studies, saliva-derived biomarkers offer distinct opportunities for studies examining the etiology of social disparities in lifespan development. First, aberrant secretion of the stress hormone cortisol measured in saliva has been assumed to be a principal mechanism by which social disparities affect childhood cognition, because cortisol can regulate the expression of genes, i.e. have epigenetic effects. However, despite the popularity of cortisol as a biomarker for adversity, little is known about whether cortisol output a) consistently differs by social inequality and b) what the genetic architecture of different measures of cortisol output is. Second, new advances of genome-wide technology and “omic” approaches have now quantified epigenetic signatures, such as DNA-methylation patterns, of a host of exposures, biological processes, and phenotypes. However, no work has been conducted to determine whether salivary DNA-methylation measures are sensitive to social inequality and associated with psychological development in children and adolescents. The present project empirically examined whether cortisol secretion and salivary DNA-methylation profiles are candidate biomarkers of social inequality experienced during childhood and adolescence that may be mechanistically involved in generating social disparities in cognitive development. Our analyses in 8-14-year-old children from the Texas Twin Project – a large, genetically-informed population-representative pediatric sample – found that there are few differences between advantaged and disadvantaged children in their cortisol output. Further, we found that genetic factors regulating salivary cortisol response to stress are separable from those regulating baseline cortisol levels, diurnal variation in cortisol, and hair cortisol levels. Different measures of cortisol secretion are thus largely distinct indices of hypothalamuspituitary-adrenal axis activity that are unlikely to be uniformly affected by adversity. Overall, we find limited support for alteration in cortisol secretion as a mechanism for the developmental consequences of socioeconomic inequality in childhood. Following preregistered analyses of epigenetic data from 1,183 8- to 19-year-olds from the Texas Twin Project, we find that children growing up in more disadvantaged families and neighborhoods and children from marginalized racial/ethnic groups exhibit DNA-methylation profiles associated with higher chronic inflammation, lower cognitive functioning, and a faster pace of biological aging. Further, these salivary DNA-methylation profiles were associated with processing speed, general executive function, perceptual reasoning, verbal comprehension, reading, and math. Our findings suggest that salivary DNA-methylation profiles – unlike cortisol measures – are promising candidate biomarkers of economic and racial inequality experienced in real-time during childhood and are associated with children’s cognitive function. Given that the DNA-methylation measures we examined were originally developed in adults, our results suggest that social inequalities in childhood may affect molecular signatures in a manner that persists into adulthood. Because DNA-methylation profiling using saliva is amenable at large scale in pediatric samples, salivary DNA-methylation profiles may be useful as surrogate endpoints for assessing the effectiveness of programs and policies that aim to reduce effects of childhood social inequality on lifespan development.

Projektbezogene Publikationen (Auswahl)

  • (2019). A novel stressful environment evokes unique genetic variation in child cortisol output
    Raffington, L., Malanchini, M., Grotzinger, A. D., Madole, J. W., Engelhardt, L., Sabhlok, A., Youn, C., Patterson, M. W., Harden, P. K., & Tucker-Drob, E. M.
    (Siehe online unter https://doi.org/10.1101/856658)
  • (2020). Polygenic scores in developmental psychology: Invite genetics in, leave biodeterminism behind. Annual Review of Developmental Psychology, 2(1), 389-411
    Raffington, L., Mallard, T., & Harden, P. K.
    (Siehe online unter https://doi.org/10.1146/annurev-devpsych-051820-123945)
  • (2020). Weak and uneven associations of home, neighborhood and school environments with stress hormone output across multiple time scales. Molecular Psychiatry, 1-16
    Malanchini, M., Engelhardt, L. E., Raffington, L., Sabhlok, A., Grotzinger, A. D., Briley, D. A., Madole, J. W., Freis, S. A., Patterson, M. W., Harden, P. K., & Tucker-Drob, E. M.
    (Siehe online unter https://doi.org/10.1038/s41380-020-0747-z)
  • (2021). Socially stratified epigenetic profiles are associated with cognitive functioning in children and adolescents
    Raffington, L., Tanksley, P., Sabhlok, A., Vinnik, L., Mallard, T., King, L., Goosby, B., Harden, K. P., & Tucker-Drob, E. M.
    (Siehe online unter https://doi.org/10.1101/2021.08.19.456979)
  • (2021). Socioeconomic disadvantage and the pace of biological aging in children. Pediatrics, 147(6)
    Raffington, L., Belsky, D. W., Kothari, M., Malanchini, M., Tucker-Drob, E. M., & Harden, K. P.
    (Siehe online unter https://doi.org/10.1542/peds.2020-024406)
 
 

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