Publications

2017
Mitchell, Colter, et al.Father loss and child telomere length.”. Pediatrics 140.2 (2017): , 140, 2, e20163245. Print.
James, Sarah, et al.Sleep Duration and Telomere Length in Children.”. The Journal of Pediatrics S0022-3476.17 (2017): , S0022-3476, 17, 30635-2. Web. Publisher's VersionAbstract

Objective

To test the association between sleep duration and telomere length in a pediatric population.

Study design

We analyzed cross-sectional data for 1567 children from the age 9 study wave of the Fragile Families and Child Wellbeing Study, a population-based birth cohort of children born between 1998 and 2000 in large American cities (population >200 000). We measured telomere length using quantitative polymerase chain reaction, and children's typical nightly sleep duration was reported by their primary caregivers. Using linear regression, we estimated the association between sleep duration and telomere length both in unadjusted models and adjusting for a number of covariates.

Results

We found that children with shorter sleep durations have shorter telomeres than children with longer sleep durations. Each hour less of nightly sleep duration is associated with having telomeres that are 0.015 log-kilobases per chromosome shorter (P < .05). We found no difference in this association by race, sex, or socioeconomic status.

Conclusions

We provide preliminary evidence that children with shorter sleep durations have shorter telomeres. This finding is consistent with a broader literature indicating that suboptimal sleep duration is a risk for increased physiological stress and impaired health. Future research should address the limitations of our study design by using longitudinal study designs and telomere measurements, measuring sleep duration via polysomnography or actigraphy, and assessing the intermediate biological mechanisms of the link between sleep and telomere dynamics.

2016
Traube, Chani, et al.Cost Associated With Pediatric Delirium in the ICU.”. Crit Care Med 44.12 (2016): , 44, 12, e1175-e1179. Web.Abstract
OBJECTIVE: To determine the costs associated with delirium in critically ill children. DESIGN: Prospective observational study. SETTING: An urban, academic, tertiary-care PICU in New York city. PATIENTS: Four-hundred and sixty-four consecutive PICU admissions between September 2, 2014, and December 12, 2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All children were assessed for delirium daily throughout their PICU stay. Hospital costs were analyzed using cost-to-charge ratios, in 2014 dollars. Median total PICU costs were higher in patients with delirium than in patients who were never delirious ($18,832 vs$4,803; p < 0.0001). Costs increased incrementally with number of days spent delirious (median cost of $9,173 for 1 d with delirium,$19,682 for 2-3 d with delirium, and \$75,833 for > 3 d with delirium; p < 0.0001); this remained highly significant even after adjusting for PICU length of stay (p < 0.0001). After controlling for age, gender, severity of illness, and PICU length of stay, delirium was associated with an 85% increase in PICU costs (p < 0.0001). CONCLUSIONS: Pediatric delirium is associated with a major increase in PICU costs. Further research directed at prevention and treatment of pediatric delirium is essential to improve outcomes in this population and could lead to substantial healthcare savings.
Mitchell, Colter, Lisa M Schneper, and Daniel A Notterman. “DNA methylation, early life environment, and health outcomes.”. Pediatr Res 79.1-2 (2016): , 79, 1-2, 212-9. Web.Abstract
Epigenetics, and especially DNA methylation, have recently become provocative biological explanations for early-life environmental effects on later health. Despite the large increase in papers on the topic over the last few years, many questions remain with regards to the biological feasibility of this mechanism and the strength of the evidence to date. In this review, we examine the literature on early-life effects on epigenetic patterns, with special emphasis on social environmental influences. First, we review the basic biology of epigenetic modification of DNA and debate the role of early-life stressful, protective, and positive environments on gene-specific, system-specific, and whole-genome epigenetic patterns later in life. Second, we compare the epigenetic literatures of both humans and other animals and review the research linking epigenetic patterns to health in order to complete the mechanistic pathway. Third, we discuss physical environmental and social environmental effects, which have to date, generally not been jointly considered. Finally, we close with a discussion of the current state of the area's research, its future direction, and its potential use in pediatric health.
Schneper, Lisa M, et al.Early-Life Experiences and Telomere Length in Adult Rhesus Monkeys: An Exploratory Study.”. Psychosom Med 78.9 (2016): , 78, 9, 1066-1071. Web.Abstract
2015
Mitchell, Colter, et al.Family structure instability, genetic sensitivity and child wellbeing”. Journal of Sociology 120.4 (2015): , 120, 4, 1195-1225. Print.
Notterman, Daniel A, and Colter Mitchell. “Epigenetics and Understanding the Impact of Social Determinants of Health.”. Pediatr Clin North Am 62.5 (2015): , 62, 5, 1227-40. Web.Abstract
Recently, a new research agenda emphasizing interactions between social factors and health has emerged. The term social determinant of health often refers to any nonmedical factor directly influencing health. Health across the life span is strongly and adversely affected by social disadvantage. Research in epigenetics indicates that alterations in DNA methylation may provide a causal link between social adversity and health disparity. Likewise, accelerated loss of telomeres is correlated with chronic stress. Research is still required to develop an understanding of the role of epigenetics and perturbed telomere function in linking social adversity with health outcome.
2014
Cheng, YW, et al.High incidence of LRAT promoter hypermethylation in colorectal cancer correlates with tumor stage.”. Medical Oncology 31.11 (2014): , 31, 11, 254. Print.
Mitchell, Colter, et al.Social disadvantage, genetic sensitivity, and children's telomere length”. PNAS 111.16 (2014): , 111, 16, 5944-5949. Web. Publisher's VersionAbstract

Disadvantaged social environments are associated with adverse health outcomes. This has been attributed, in part, to chronic stress. Telomere length (TL) has been used as a biomarker of chronic stress: TL is shorter in adults in a variety of contexts, including disadvantaged social standing and depression. We use data from 40, 9-y-old boys participating in the Fragile Families and Child Wellbeing Study to extend this observation to African American children. We report that exposure to disadvantaged environments is associated with reduced TL by age 9 y. We document significant associations between low income, low maternal education, unstable family structure, and harsh parenting and TL. These effects were moderated by genetic variants in serotonergic and dopaminergic pathways. Consistent with the differential susceptibility hypothesis, subjects with the highest genetic sensitivity scores had the shortest TL when exposed to disadvantaged social environments and the longest TL when exposed to advantaged environments.

2013
Lee, D, et al.The great recession, genetic sensitivity, and maternal harsh parenting.”. PNAS 110.34 (2013): , 110, 34, 13780-13784. Print.
Giacobbe, A, et al.p63 regulates glutaminase 2 expression”. Cell Cycle 12.9 (2013). Print.
Mitchell, Colter, et al.Genetic differential sensitivity to social environments: implications for research.”. Am J Public Health 103 Suppl 1 (2013): , 103 Suppl 1, S102-10. Web.Abstract
Researchers have proposed a genetic differential sensitivity to social environmental (GDSE) model positing that individuals with certain genetic makeups are more sensitive to favorable and unfavorable environmental influences than those without these genetic makeups. We discuss several issues facing researchers who want to use GDSE to examine health: (1) the need for greater theorizing about the social environment to properly understand the size and direction of environmental influences; (2) the potential for combining multiple genetic markers to measure an individual's genetic sensitivity to environmental influence; (3) how this model and exogenous shocks deal with gene-environment correlations; (4) implications of this model for public health and prevention; and (5) how life course and developmental theories may be used to inform GDSE research.
2011
Mitchell, Colter, et al.Role of mother's genes and environment in postpartum depression.”. Proc Natl Acad Sci U S A 108.20 (2011): , 108, 20, 8189-93. Web.Abstract
Most studies of human molecular genetics and social environment interactions on health have relied heavily on the classic diathesis-stress model that treats genetic variations and environments as being either "risky" or "protective." The biological susceptibility model posits that some individuals have greater genetic reactivity to stress, leading to worse outcomes in poor environments, but better outcomes in rich environments. Using a nontruncated measure of a chronic environmental stressor--socioeconomic status--measured by education, and two polymorphisms (5-HTTLPR and STin2 VNTR) of the serotonin transporter gene (5-HTT), we find strong evidence that some women are genetically more reactive to the environment, resulting in a crossover of risks of postpartum depression for the most reactive groups. We discuss how our approach and findings provide a framework for understanding some of the confusion in the gene-environment interaction literature on stress, 5-HTT, and depression.
2008
Cheng, Y-W, et al.CpG island methylator phenotype associates with low-degree chromosomal abnormalities in colorectal cancer”. Clinical Cancer Research 14.19 (2008): , 14, 19, 6005-6013. Print.
Bacolod, M, et al.Emerging paradigms in cancer genetics: some important findings from high-density SNP array studies.”. Cancer Research 69.3 (2008): , 69, 3, 723-727. Web. Publisher's Version
Forslund, A, et al.MDM2 gene amplification is correlated to tumor progression but not to the presence of SNP309 or TP53 mutational status in primary colorectal cancers.”. Molecular Cancer Research 62 (2008): , 6, 2, 205-211. Web. Publisher's Version
Puca, R, et al.Reversible dysfunction of wild-type p53 following HIPK2 knockdown”. Cancer Research 69.10 (2008): , 69, 10, 3703-3714. Web. Publisher's Version