13
Jul 22

Obesity and accelerated epigenetic aging in a high-risk cohort of children

New insights into mechanisms linking obesity to poor health outcomes suggest a role for cellular aging pathways, casting obesity as a disease of accelerated biological aging. Although obesity has been linked to accelerated epigenetic aging in middle-aged adults, the impact during childhood remains unclear. We tested the association between body mass index (BMI) and accelerated epigenetic aging in a cohort of high-risk children. Participants were children (N = 273, aged 8 to 14 years, 82% investigated for maltreatment) recruited to the Child Health Study, an ongoing prospective study of youth investigated for maltreatment and a comparison youth. BMI was measured as a continuous variable. Accelerated epigenetic aging of blood leukocytes was defined as the age-adjusted residuals of several established epigenetic aging clocks (Horvath, Hannum, GrimAge, PhenoAge) along with a newer algorithm, the DunedinPoAm, developed to quantify the pace-of-aging. Hypotheses were tested with generalized linear models. Higher age-and sex- adjusted z-scored BMI was significantly correlated with household income, blood cell counts, and three of the accelerated epigenetic aging measures: GrimAge (r = 0.31, P < .0001), PhenoAge (r = 0.24, P < .0001), and DunedinPoAm (r = 0.38, P < .0001). In fully adjusted models, GrimAge (β = 0.07; P = .0009) and DunedinPoAm (β = 0.0017; P < .0001) remained significantly associated with higher age- and sex-adjusted z-scored BMI. Maltreatment-status was not associated with accelerated epigenetic aging. In a high-risk cohort of children, higher BMI predicted epigenetic aging as assessed by two epigenetic aging clocks. These results suggest the association between obesity and accelerated epigenetic aging begins in early life, with implications for future morbidity and mortality risk.

CITATION: Etzel, L., Hastings, W. J., Hall, M. A., Heim, C. M., Meaney, M., Noll, J. G., Rose, E. J., Schreier, H. M. C., Shenk, C., & Shalev, I., (in press). Obesity and accelerated epigenetic aging in a high-risk cohort of children.


13
Jul 22

Comparing qPCR and DNA-Methylation-based Measurements of Telomere Length in a High-Risk Pediatric Cohort

Various approaches exist to assess population differences in biological aging. Telomere length (TL) is one such measure, and is associated with disease, disability and early mortality. Yet, issues surrounding precision and reproducibility are a concern for TL measurement. An alternative method to estimate TL using DNA methylation (DNAmTL) was recently developed. Although DNAmTL has been characterized in adult and elderly cohorts, its utility in pediatric populations remains unknown. We examined the comparability of leukocyte TL measurements generated using qPCR (absolute TL; aTL) to those estimated using DNAmTL in a high-risk pediatric cohort (N = 269; age: 8-13 years, 83% investigated for maltreatment). aTL and DNAmTL measurements were correlated with one another (r = 0.20, p = 0.001), but exhibited poor measurement agreement and were significantly different in paired-sample t-tests (Cohen’s d = 0.77, p < 0.001). Shorter DNAmTL was associated with older age (r = -0.25, p < 0.001), male sex (β = -0.27, p = 0.029), and White race (β = -0.74, p = 0.008). By contrast, aTL was less strongly associated with age (r = -0.13, p = 0.040), was longer in males (β = 0.31, p = 0.012), and was not associated with race (p = 0.820). These findings highlight strengths and limitations of high-throughput measures of TL; although DNAmTL replicated hypothesized associations, aTL measurements were positively skewed and did not replicate associations with external validity measures. These results also extend previous research in adults and suggest that DNAmTL is a sensitive TL measure for use in pediatric populations.

CITATION: Hastings, W. J., Etzel, L., Heim, C. M., Noll, J. G., Rose, E. J., Schreier, H. M. C., Shenk, C. E., Tang, X.& Shalev, I. (in press). Comparing qPCR and DNA-Methylation-based Measurements of Telomere Length in a High-Risk Pediatric Cohort. Aging.


13
Jul 22

Assembling a cohort for in-depth, longitudinal assessments of the biological embedding of child maltreatment: Methods, complexities, and lessons learned

As championed by the work of Ed Zigler, investing in nurturing environments for all children is a chief tenet of primary prevention that will have far-reaching benefits to the health and welfare of all members of society. Children who endure child maltreatment (CM) are among society’s most vulnerable. Prospective longitudinal research aimed at a comprehensive understanding of the mechanisms linking CM to subsequent adverse health consequences is needed to improve outcomes and to strengthen causal inference. This paper outlines the methods of the Child Health Study (CHS), a large, state-wide longitudinal cohort of recently maltreated and nonmaltreated youth aged 8-13 who will be assessed every 2 years. The CHS is designed to include in-depth assessments of multiple environmental, behavioral, neural, physiological, and molecular mechanisms through which CM may impact a broad spectrum of youth development, including behavioral and physical health outcomes. In addition to describing the conceptual framework and methods underlying the CHS, we provide information on valuable “lessons learned” in the hopes of supporting future research efforts facing similar challenges. The ultimate goal of this research is demonstrating how policies regarding CM impact the well-being, resilience and recovery of survivors and that they are worthy of large public investment.

CITATION: Schreier, H. M. C., Heim, C. M., Rose, E. J., Shalev, I., Shenk, C. E., & Noll, J. G. (2021). Assembling a cohort for in-depth, longitudinal assessments of the biological embedding of child maltreatment: Methods, complexities, and lessons learned. Development & Psychopathology, 33(2), 394-408.


11
Apr 16

Child maltreatment and pediatric asthma: A review of the literature

Background: Child maltreatment is a common problem with known adverse consequences, yet its contributions to the development and course of pediatric asthma are only poorly understood. Main: This review first describes possible pathways connecting child maltreatment to pediatric asthma, including aspects of the physical home environment, health behaviors and disease management, and psychological consequences of child maltreatment. We subsequently review existing studies, which generally report an association between maltreatment experiences and asthma outcomes in childhood. However, this literature is in its early stages; there are only a handful studies, most of them rely on self-reports of both child maltreatment and asthma history, and none have investigated the physiological underpinnings of this association. Taken together, however, the studies are suggestive of child maltreatment playing a role in pediatric asthma incidence and expression that should be explored further. Conclusion: Existing data are sparse and do not allow for specific conclusions. However, the data are suggestive of child maltreatment influencing asthma risk and morbidity long before the adult years. Future research should focus on understanding how child maltreatment contributes to asthma disease risk and progression in this highly vulnerable population.
CITATION: Schreier, H. M. C., Chen, E. & Miller, G. E. (2016). Child maltreatment and pediatric asthma: a review of the literature. Asthma Research and Practice, 2(7).

15
Sep 15

Resilience in low socioeconomic status children with asthma: adaptations to stress

Background: Low socioeconomic status (SES) is a strong predictor of many health problems, including asthma impairment; however, little is understood about why some patients defy this trend by exhibiting good asthma control despite living in adverse environments. Objective: This study sought to test whether a psychological characteristic, the shift-and-persist strategy (dealing with stressors by reframing them more positively while at the same time persisting in optimistic thoughts about the future), protects low-SES children with asthma. Methods: One hundred twenty-one children aged 9 to 18 years with a physician’s diagnosis of asthma were recruited from medical practices and community advertisements (mean age, 12.6 years; 67% male; 61% white). Shift-and-persist scores and asthma inflammation (eosinophil counts and stimulated IL-4 cytokine production) were assessed at baseline, and asthma impairment (daily diary measures of rescue inhaler use and school absences) and daily peak flow were monitored at baseline and at a 6-month follow-up. Results: Children who came from low-SES backgrounds but who engaged in shift-and-persist strategies displayed less asthma inflammation at baseline (β = 0.19, P < .05), as well as less asthma impairment (reduced rescue inhaler use and fewer school absences; β = 0.32, P < .01) prospectively at the 6-month follow-up period. In contrast, shift-and-persist strategies were not beneficial among high-SES children with asthma. Conclusion: An approach that focuses on the psychological qualities that low-SES children develop to adapt to stressors might represent a practical and effective starting point for reducing health disparities. Moreover, the approaches that are effective in low-SES communities might be different from those that are optimal in a high-SES context.

CITATION: Chen, E., Strunk, R. C., Threthewey, A., Schreier, H. M. C., Maharaj, N., & Miller, G. E. (2011). Resilience in low socioeconomic status children with asthma: adaptations to stress. Journal of Asthma and Clinical Immunology, 128(5), 970-976.


09
Sep 15

Socioeconomic status and the health of youth: A multi-level, multi-domain approach to conceptualizing pathways

Previous research has clearly established associations between low socioeconomic status (SES) and poor youth physical health outcomes. This article provides an overview of the main pathways through which low SES environments come to influence youth health. We focus on 2 prevalent chronic health problems in youth today, asthma and obesity. We review and propose a model that encompasses (a) multiple levels of influence, including the neighborhood, family and person level; (b) both social and physical domains in the environment; and finally (c) dynamic relationships between these factors. A synthesis of existing research and our proposed model draw attention to the notion of adverse physical and social exposures in youth’s neighborhood environments altering family characteristics and youth psychosocial and behavioral profiles, thereby increasing youth’s risk for health problems. We also note the importance of acknowledging reciprocal influences across levels and domains (e.g., between family and child) that create self-perpetuating patterns of influence that further accentuate the impact of these factors on youth health. Finally, we document that factors across levels can interact (e.g., environmental pollution levels with child stress) to create unique, synergistic effects on youth health. Our model stresses the importance of evaluating influences on youth’s physical health not in isolation but in the context of the broader social and physical environments in which youth live. Understanding the complex relationships between the factors that link low SES to youth’s long-term health trajectories is necessary for the creation and implementation of successful interventions and policies to ultimately reduce health disparities.

CITATION: Schreier, H. M. C. & Chen, E. (2013). Socioeconomic status and the health of youth: A multi-level, multi-domain approach to conceptualizing pathways. Psychological Bulletin, 139(3), 606-654.


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