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Publications — No Comments
13
Apr 23

Investigating the effects of maltreatment and acute stress on the concordance of blood and DNA methylation methods of estimating immune cell proportions

Background

Immune cell proportions can be used to detect pathophysiological states and are also critical covariates in genomic analyses. The complete blood count (CBC) is the most common method of immune cell proportion estimation, but immune cell proportions can also be estimated using whole-genome DNA methylation (DNAm). Although the concordance of CBC and DNAm estimations has been validated in various adult and clinical populations, less is known about the concordance of existing estimators among stress-exposed individuals. As early life adversity and acute psychosocial stress have both been associated with unique DNAm alterations, the concordance of CBC and DNAm immune cell proportion needs to be validated in various states of stress.

Results

We report the correlation and concordance between CBC and DNAm estimates of immune cell proportions using the Illumina EPIC DNAm array within two unique studies: Study 1, a high-risk pediatric cohort of children oversampled for exposure to maltreatment (N = 365, age 8 to 14 years), and Study 2, a sample of young adults who have participated in an acute laboratory stressor with four pre- and post-stress measurements (N = 28, number of observations = 100). Comparing CBC and DNAm proportions across both studies, estimates of neutrophils (r = 0.948, p < 0.001), lymphocytes (r = 0.916, p < 0.001), and eosinophils (r = 0.933, p < 0.001) were highly correlated, while monocyte estimates were moderately correlated (r = 0.766, p < 0.001) and basophil estimates were weakly correlated (r = 0.189, p < 0.001). In Study 1, we observed significant deviations in raw values between the two approaches for some immune cell subtypes; however, the observed differences were not significantly predicted by exposure to child maltreatment. In Study 2, while significant changes in immune cell proportions were observed in response to acute psychosocial stress for both CBC and DNAm estimates, the observed changes were similar for both approaches.

Conclusions

Although significant differences in immune cell proportion estimates between CBC and DNAm exist, as well as stress-induced changes in immune cell proportions, neither child maltreatment nor acute psychosocial stress alters the concordance of CBC and DNAm estimation methods. These results suggest that the agreement between CBC and DNAm estimators of immune cell proportions is robust to exposure to child maltreatment and acute psychosocial stress.

CITATION: Apsley, A.T., Etzel, L., Hastings, W.J. et al. Investigating the effects of maltreatment and acute stress on the concordance of blood and DNA methylation methods of estimating immune cell proportions. Clin Epigenet 15, 33 (2023). https://doi.org/10.1186/s13148-023-01437-5

Publications — No Comments
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.

Publications — No Comments
13
Jul 22

The Flexible Regulation of Emotional Expression Scale for Youth (FREE-Y): Adaptation and Validation Across a Varied Sample of Children and Adolescents

Flexible self-regulation has been shown to be an adaptive ability. This study adapted and validated the adult Flexible Regulation of Emotional Expression (FREE) Scale for use with youth (FREE-Y) in community and maltreatment samples. The FREE-Y measures the ability to flexibly enhance and suppress emotion expression across an array of hypothetical social scenarios. Participants (N = 654, 8-19 years) were included from three studies. Confirmatory factor analysis (CFA) confirmed a theoretically appropriate higher order factor structure. Using multiple-group CFAs, measurement invariance was achieved across maltreatment status, age, and gender. Reliabilities were adequate and construct validity was demonstrated through associations with measures of emotion regulation, psychopathology, IQ, and executive functioning. Group comparisons indicated lower Suppression and Flexibility scores for maltreated versus comparison participants. Findings suggest that the FREE-Y is a valid measure of expressive regulation ability in youth that can be applied across a range of populations.

CITATION: Haag, A.-C., Cha, C. B., Noll, J. G., Gee, D. G., Shenk, C. E., Schreier, H. M. C., Heim, C., Shalev, I., Rose, E. J., Jorgensen, A., & Bonanno, G. A. (in press). Adaptation and validation of      the Flexible Regulation of Emotional Expression Scale for Youth (FREE-Y). Assessment.

Publications — No Comments
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.

Publications — No Comments
13
Jul 22

The intergenerational interplay of adversity on salivary inflammation in young children and caregivers

Systemic inflammation links exposure to early childhood adversity to later disease. The associations among adversity and disease risk might in part operate through poor oral hygiene and subsequent periodontal inflammation, which can be measured in saliva. Few studies, however, have examined the association between adversity and salivary inflammation in young children. Further, there is a dearth of literature investigating adverse experiences and salivary inflammation in children and caregivers together, limiting our understanding of the intergenerational, dual effects of adversity on inflammation for both members of the caregiver-child dyad. This study tested child and caregiver adversity and their associations with an inflammatory composite (i.e., IL-6, IL-1β, IL-8, TNF-α) and CRP in 93 preschool-age children and their caregivers. Caregivers reported on their child’s experiences of adversity, as well as on their own adverse experiences, using a comprehensive questionnaire synthesized from previous checklists for complete coverage of possible adverse events. Results showed that caregivers’ salivary inflammatory markers (i.e., IL-6, IL-1β, IL-8, TNF-α, and CRP) were not significantly correlated with the same five inflammatory markers in children’s saliva. Among children, adversity was associated with significantly higher levels of the inflammatory composite, though not CRP. This association was amplified among children whose caregivers also experienced more adversity during adulthood. Among caregivers, childhood adversity and adulthood adversity were each independently associated with significantly higher levels of the inflammatory composite and CRP. The association between caregivers’ own childhood adversity and inflammation was amplified among caregivers whose children also experienced more adversity during their childhoods. These findings provide preliminary evidence for the possible dual role of young children’s and caregivers’ adverse experiences in contributing to salivary inflammation for both members of the dyad, suggesting possible implications for systemic inflammation and future disease.

CITATION: Huffhines, L., Jackson, Y., McGuire, A. B. & Schreier, H. M. C. (2021). The intergenerational interplay of adversity on salivary inflammation in young children and caregivers. Psychoneuroendocrinology, 128, 105222.

Publications — No Comments
13
Jul 22

Childhood physical neglect is associated with exaggerated systemic and intracellular inflammatory responses to repeated psychosocial stress in adulthood

Experiences of child maltreatment are associated with a host of adverse mental and physical health outcomes in adulthood. Altered reactivity to psychosocial stress exposure may partially explain known associations between early experiences of maltreatment and later life health. The present study focuses on examining whether experiences of child maltreatment are associated with physiological reactions to initial and repeated psychosocial stress in adulthood. To this end, 44 healthy adults (52% male, aged 18-65) completed the Childhood Trauma Questionnaire to provide information about exposure to child maltreatment and completed the Trier Social Stress Test (TSST) on 2 consecutive days. Peripheral blood was collected prior to as well as 30 and 120 min following the TSST on each day. Plasma Interleukin-6 (IL-6) and gene expression of IL-6, IL-1β, nuclear factor-kB (NF-kB), and inhibitor of kB (IkB) were measured from each blood sample. Total CTQ scores were unrelated to plasma IL-6 and gene expression (ps > .10) but a history of childhood physical neglect was associated with increased interleukin-1β (β =.35; p =.02; R2 =.19) and nuclear factor-kB (β =.30; p =.046; R2 =.13) expression following initial stress. Following repeated exposure to the TSST, childhood physical neglect was associated with increased plasma IL-6 reactivity (β =.34; p =.02; R2 =.16) and increased expression of nuclear factor-kB (β =.31; p =.04; R2 =.08). Finally, childhood physical neglect was associated with decreased habituation following repeated exposure to the TSST. Other CTQ subscales were not related to plasma IL-6 and gene expression when considered individually. Results from this study are suggestive of a unique effect of childhood physical neglect on the physiological stress response following initial and repeated exposure to a common psychosocial stressor. This provides important directions for future research because the effect of childhood physical neglect on long-term neglect are not well understood and in need of further investigation.

CITATION: Schreier, H. M. C., Kuras, Y. I., McInnis, C. M., Thoma, M. V., Gianferante, D., Hanlin, L., Chen, X., Wang, D., Goldblatt, D. & Rohleder, N. (2020). Childhood physical neglect is associated with exaggerated systemic and intracellular inflammatory responses to repeated psychosocial stress in adulthood. Frontiers Psychiatry, 11, 504.

Chronic Illnesses / Publications / Trauma — No Comments
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).
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