2019 — 2021 |
Bogdan, Ryan H Oltmanns, Thomas [⬀] |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Intergenerational Transmission of Stress: Psychosocial and Biological Mechanisms
PROJECT SUMMARY/ABSTRACT Despite growing evidence that health outcomes are perpetuated across generations, empirical examinations of putative mechanisms underlying this intergenerational transmission are lacking. Explanatory mechanisms often focus on stress, which manifests in both psychological and physical symptoms. Relevant pathways have primarily been tested within a single generation or in non-human animal research. From mouse to man, evidence suggests that interplay across stress-related biological (e.g., cortisol, inflammation, telomeres) and psychosocial (e.g., social integration, health behaviors) factors critically contribute to the intergenerational transmission of health. The proposed study will examine the psychosocial ad biological mechanisms through which adversity transmits adverse mental and physical health outcomes across 3 generations and promotes the maintenance of health disparities. To this end, we will leverage a large (G1, n=1,630) and diverse (33% African-American) sample of older adults (currently aged 64-73) enrolled in an ongoing NIH-funded longitudinal study of stress and health and recruit their children (G2, n=2,200) and grandchildren (G3, n=1,900) to complete self-report questionnaires assessing stress, psychosocial factors, and health. From these, a subsample of 300 (150 Black and 150 White) G1/G2/G3 triads (total N=900) will visit our lab to provide blood and saliva measures so that we may assay the stress hormone cortisol, as well as inflammation markers. We will assay both their basal function and evoked activity. Triads and dyads will return to the lab 2.5 years later for a repeat assessment. All measures will be integrated with existing G1 data from our ongoing longitudinal samples. Investigating the intergenerational transmission of stress-related psychosocial and biological factors promises to inform our understanding of how health outcomes and racial health disparities are perpetuated across generations and, may, ultimately guide targeted prevention and public policy.
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0.957 |
2019 — 2020 |
Bogdan, Ryan H |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Modeling Poly-Genomic Risk in the Relationship Between Brain Structure and Alcohol Involvement From Adolescence Through Adulthood
PROJECT SUMMARY/ABSTRACT Alcohol use is associated with significant personal and socioeconomic costs (accounting for more than 5% of global disease burden as well as worldwide deaths). Alcohol use initiation, progression to heavy episodic drinking, and early onset alcohol use disorder commonly emerge during adolescence and young adulthood. This developmental period of risk is theorized to result from typical patterns of regionally asynchronous brain maturation (i.e., rapid and early development of limbic regions alongside relatively immature prefrontal and multimodal association cortices) resulting in a diminished ability to suppress inappropriate emotions, desires, and actions when salient environmental cues are present. During later young adulthood the stabilization, reduction, or desistance of heavy use typically occurs alongside maturing cognitive control and emotional regulation abilities coinciding with cortical development. Brain maturation may also be influenced by alcohol use. However, whether alcohol use alters brain maturation and/or results from individual differences in neural development attributable to predipsositional genomic background is unclear and can only be addressed by genomically-informed longitudinal research with extensive alcohol phenotyping. In this 2-year R21, we propose to add genome-wide association study (GWAS) content to 2 longitudinal neuroimaging studies of adolescents and young adults (n=696; spanning ages 12-33 with annual neuroimaging and biannual alcohol characterization) to examine whether brain changes during adolescence and young adulthood associated with alcohol use may represent polygenic risk factors and/or represent consequences of heavy alcohol exposure. Disentangling the contributions of predisposing factors from consequences of alcohol on structural brain trajectories will inform our etiologic understanding of alcohol use during adolescence and young adulthood that could contribute to alcohol- related policy, education, nosology, prevention, and treatment. Primary deliverables from this project will be manuscripts examining whether polygenic propensity to alcohol use, as well as risk for impulsivity and negative affect and deficits in cognition, modify trajectories of brain maturation and further alter the course of youth alcohol engagement. Further, due to the extensive scope of longitudinal data available in these studies (e.g., other neural phenotypes, psychiatric, sleep, trauma, biosensor assessments), the addition of GWAS data will provide benefits to the broader research community through data sharing (e.g., dbGaP) and contribute to consortia-based gene discovery efforts (e.g., ENIGMA, PGC).
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0.957 |
2021 |
Bogdan, Ryan H Rogers, Cynthia E [⬀] |
U01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
23/24 Healthy Brain and Child Development National Consortium
Project Summary/Abstract Neurodevelopmental processes are shaped by dynamic interactions between genes and environments. Maladaptive experiences early in life can alter developmental trajectories, leading to harmful and enduring developmental sequelae. Pre- and postnatal hazards include maternal substance exposure, toxicant exposures in pregnancy and early life, maternal health conditions, parental psychopathology, maltreatment, structural racism, and excessive stress. To elucidate how various environmental hazards impact child development, it is imperative that a normative template of developmental trajectories over the first 10 years of life be established based on a sufficiently large and demographically diverse sample of the US population. To accomplish this, the Healthy Brain and Child Development National Consortium (HBCD-NC) has been formed to deploy a harmonized, optimized, and innovative set of neuroimaging (MRI, EEG) measures complemented by an extensive battery of behavioral, physiological, and psychological tools, and biospecimens to understand neurodevelopmental trajectories in a sample of 7,500 mothers and infants enrolled at 24 sites across the United States (US). The HBCD-NC will carry out a common research protocol under direction of the HBCD-NC Administrative Core (HCAC) and will assemble and distribute a comprehensive and well-curated research dataset to the scientific community at large under the direction of the HBCD-NC Data Coordinating Center (HDCC). The overarching goal of the HBCD-NC is to create a comprehensive, harmonized, and high- dimensional dataset that will characterize typical neurodevelopmental trajectories in US children and that will assess how biological and environmental exposures affect those trajectories. A special emphasis will be placed on understanding the impact of pre- and postnatal exposure to opioids, marijuana, alcohol, tobacco and/or other substances. To address these broad objectives, the sample of women enrolled will include: 1) a racially, ethnically, and socioeconomically diverse cohort that is representative of the US population; 2) pregnant woman with use of targeted substances (opioids, marijuana, alcohol, tobacco); and 3) demographically and behaviorally similar women without substance use in pregnancy to enable valid causal inferences. In addition, the HBCD-NC will identify key developmental windows during which both harmful and protective environments have the most influence on later neurodevelopmental outcomes. The large, multi-modal, longitudinal, and generalizable dataset that will be produced for the first time by this study will provide novel insights into child development using state- of-the-art methods. The HBCD-NC study will inform public policy to improve the health and development of children across the nation.
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0.957 |