Grant Number:
Principal Investigator:
Wright, Robert O
Institution:
Brigham and Women's Hospital
Most Recent Award Year:
2012
Lifestage of Participants:
Exposure:
Prenatal; Infant (0-1 year); Youth (1-18 years); Adulthood (mother)
Assessment:
Prenatal; Infant (0-1 year); Youth (1-18 years)
Exposures:
Metals:
Lead
Mixtures:
Non-Chemical Stress:
Psychosocial stress
Health Outcomes:
Neurological/Cognitive Outcomes:
Neurobehavioral outcomes; Neurodevelopmental outcomes
Biological Sample:
Saliva/buccal cells
Other Participant Data:
Behavioral/Cognitive tests; Questionnaire
Abstract:
Previous studies on lead have typically analyzed covariate markers of social stress as independent predictors of neurodevelopment, considering them potential confounders. There are biological reasons to believe that psychosocial stress potentiates the toxicity of lead. If so, then understanding this relationship may be the key to designing effective public health interventions designed to improve neurodevelopment in children. The ELEMENT cohort has created the infrastructure for such a study and is uniquely positioned to address these important neurotoxicological questions. In this competing renewal, we hypothesize that lead exposure and social stressors experienced jointly in pregnancy and infancy will have multiplicatively increased deleterious effects on neurodevelopment (i.e. environment X environment interactions). Based on work conducted by others in animals, this should result in selective impairments in memory (hippocampus) and fixed interval responses (nucleus accumbens) due to the established vulnerability of these structures to stress and lead. Our results thus far have established a consistent pattern of adverse effects to both lead and social stress, as well as disturbed salivary cortisol rhythms following high levels of stress. We also find multiplicative changes in cortisol rhythms when these exposures occur in the context of high lead exposure. Cortisol may thus represent a mechanistic link between lead and stress. We have already enrolled 1000 infants in Mexico City measuring stress and lead exposure longitudinally beginning in the 2nd trimester through age 2 years. To date, we have measured only infant development via Bayley Scales. In this renewal we propose to measure more detailed neurophenotypes as the children age (behavior, cognition, memory) as well as tests specific to hippocampal and nucleus accumbens function. Social and educational interventions, if targeted properly, could be effective treatments. This research will identify those interventions.
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Related NIEHS-Funded Study Populations
Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT)
Principal Investigator:
Hu, Howard; Peterson, Karen; Hernandez-Avila, Mauricio; Tellez-Rojo, Martha Maria
| Study Population Page Study Population c49
Institution:
University of Michigan
Location:
Mexico City, Mexico
Number of Participants::
1,653
Brief Description::
This is a group of three sequentially-enrolled, on-going, epidemiologic birth cohort studies in Mexico City with an original aim to investigate the impact of lead on child development. The research aims have since expanded to include a wide range health outcomes and environmental, nutritional, behavioral, genetic, and epigenetic risk factors. More than 1,600 mother-child pairs enrolled in the study beginning in 1994, some of whom have been followed for over two decades.