Browsing by Subject "Receptors, Glucocorticoid"

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    Can Genetics Predict Response to Complex Behavioral Interventions? Evidence from a Genetic Analysis of the Fast Track Randomized Control Trial.
    (J Policy Anal Manage, 2015) Albert, Dustin; Belsky, Daniel W; Crowley, D Max; Latendresse, Shawn J; Aliev, Fazil; Riley, Brien; Group, Conduct Problems Prevention Research; Dick, Danielle M; Dodge, Kenneth A
    Early interventions are a preferred method for addressing behavioral problems in high-risk children, but often have only modest effects. Identifying sources of variation in intervention effects can suggest means to improve efficiency. One potential source of such variation is the genome. We conducted a genetic analysis of the Fast Track randomized control trial, a 10-year-long intervention to prevent high-risk kindergarteners from developing adult externalizing problems including substance abuse and antisocial behavior. We tested whether variants of the glucocorticoid receptor gene NR3C1 were associated with differences in response to the Fast Track intervention. We found that in European-American children, a variant of NR3C1 identified by the single-nucleotide polymorphism rs10482672 was associated with increased risk for externalizing psychopathology in control group children and decreased risk for externalizing psychopathology in intervention group children. Variation in NR3C1 measured in this study was not associated with differential intervention response in African-American children. We discuss implications for efforts to prevent externalizing problems in high-risk children and for public policy in the genomic era.
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    Stress biomarkers and child development in young children in Bangladesh.
    (Psychoneuroendocrinology, 2024-03) Butzin-Dozier, Zachary; Mertens, Andrew N; Tan, Sophia T; Granger, Douglas A; Pitchik, Helen O; Il'yasova, Dora; Tofail, Fahmida; Rahman, Md Ziaur; Spasojevic, Ivan; Shalev, Idan; Ali, Shahjahan; Karim, Mohammed Rabiul; Shahriar, Sunny; Famida, Syeda Luthfa; Shuman, Gabrielle; Shoab, Abul K; Akther, Salma; Hossen, Md Saheen; Mutsuddi, Palash; Rahman, Mahbubur; Unicomb, Leanne; Das, Kishor K; Yan, Liying; Meyer, Ann; Stewart, Christine P; Hubbard, Alan E; Naved, Ruchira Tabassum; Parvin, Kausar; Mamun, Md Mahfuz Al; Luby, Stephen P; Colford, John M; Fernald, Lia CH; Lin, Audrie

    Background

    Hundreds of millions of children in low- and middle-income countries are exposed to chronic stressors, such as poverty, poor sanitation and hygiene, and sub-optimal nutrition. These stressors can have physiological consequences for children and may ultimately have detrimental effects on child development. This study explores associations between biological measures of chronic stress in early life and developmental outcomes in a large cohort of young children living in rural Bangladesh.

    Methods

    We assessed physiologic measures of stress in the first two years of life using measures of the hypothalamic-pituitary-adrenal (HPA) axis (salivary cortisol and glucocorticoid receptor gene methylation), the sympathetic-adrenal-medullary (SAM) system (salivary alpha-amylase, heart rate, and blood pressure), and oxidative status (F2-isoprostanes). We assessed child development in the first two years of life with the MacArthur-Bates Communicative Development Inventories (CDI), the WHO gross motor milestones, and the Extended Ages and Stages Questionnaire (EASQ). We compared development outcomes of children at the 75th and 25th percentiles of stress biomarker distributions while adjusting for potential confounders using generalized additive models, which are statistical models where the outcome is predicted by a potentially non-linear function of predictor variables.

    Results

    We analyzed data from 684 children (49% female) at both 14 and 28 months of age; we included an additional 765 children at 28 months of age. We detected a significant relationship between HPA axis activity and child development, where increased HPA axis activity was associated with poor development outcomes. Specifically, we found that cortisol reactivity (coefficient -0.15, 95% CI (-0.29, -0.01)) and post-stressor levels (coefficient -0.12, 95% CI (-0.24, -0.01)) were associated with CDI comprehension score, post-stressor cortisol was associated with combined EASQ score (coefficient -0.22, 95% CI (-0.41, -0.04), and overall glucocorticoid receptor methylation was associated with CDI expression score (coefficient -0.09, 95% CI (-0.17, -0.01)). We did not detect a significant relationship between SAM activity or oxidative status and child development.

    Conclusions

    Our observations reveal associations between the physiological evidence of stress in the HPA axis with developmental status in early childhood. These findings add to the existing evidence exploring the developmental consequences of early life stress.