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Cincinnati Children's Environmental Health Center (2001-2006)
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Principal Investigator: Bruce Lanphear, MD MPH
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The Center studies neurobehavioral effects of prevalent toxicants. This requires an interdisciplinary organization with each component contributing to the overall goal. All of the five research projects in the Center focus on the linkage of exposures to prevalent environmental toxicants with neurobehavioral outcomes. The projects are:
- Identifying and defining causes of developmental disorders, behavioral problems, growth retardation and hearing loss due to environmental toxicants;
- Developing and validating biomarkers for in utero exposures and environmental monitoring methods for exposure and risk characterization;
- Using rigorous epidemiologic methods to test the safety and efficacy of interventions to reduce exposures to prevalent environmental toxicants;
- Identifying adverse effects of lead exposure on social functions, delinquent behaviors and incarceration, conduct disorders, and features consistent with ADHD in early adulthood; and
- Assisting community members to identify and ultimately protect their children from adverse effects linked with environmental toxicants.
Primary Exposures: Prevalent toxicants, including lead, methyl mercury, PCBs, pesticides, ETS (as measured by cotinine level).
Primary Outcomes: Adverse neurobehavioral effects, growth delay, hearing loss, developmental disorders, asthma, behavior problems (including conduct disorder and ADHD), impaired intellectual abilities, dental caries and injuries.
The Cincinnati Children’s Center has been pursuing five research projects.
Project 1, "Neurobehavioral Effects of Prevalent Toxicants in Children" is assessing the risks of environmental exposures during two critical developmental phases: in utero and in early childhood. This includes a nested, randomized controlled trial to assess the efficacy of lead hazard controls on the development of adverse neurobehavioral effects.
Project 2, "Validation of Meconium Markers of Fetal Neurotoxicant Exposures” is testing the hypothesis that meconium samples can be used for simultaneous analysis of several different environmental neurotoxicants to which the fetus is exposed.
Project 3, a community-based research project "Identifying Residential Hazards Using Home Test Kits" is testing and validating tools for community members to assess levels of contaminants in their home environment.
The goal of Project 4, "Early Exposure to Lead and Adult Antisocial Outcome" is to examine the relationship between early prenatal and postnatal exposure to lead and antisocial behavior in adulthood.
Project 5, "MR Assessment of Brain Function Altered by Lead Exposure" seeks to better understand the relationship of environmental lead exposure with alterations in brain neurochemistry, structure, and function using magnetic resonance methods.
Research Projects – Detailed Descriptions
The Cincinnati Children’s Center has shown that exposure to lead and prenatal tobacco exposure are implicated as precursors of attention deficit hyperactivity disorder (ADHD) in children. The Center has, for example, conducted studies linking gene-environment interactions - dopamine–associated polymorphisms, DAT1 and DRD4 with lead and tobacco exposure - with ADHD in children. These studies indicate that children with high-risk dopamine-associated polymorphisms are more susceptible to lead and tobacco exposure. Males were at particular risk for lead-associated executive dysfunction. Researchers also found that childhood lead exposure and prenatal tobacco exposure are risk factors for doctor-diagnosed ADHD, possibly accounting for as much as 1 out of 3 cases of ADHD in U.S. children (Kahn et al 2003, Braun et al 2006, Froehlich et al 2006 [in press])
Using functional magnetic resonance imaging (fMRI), subjects were shown a series of nouns and asked to think of verbs associated with them. Researchers observed diminished activity in one region of the brain and augmented activity in a separate region. A composite functional MRI map (below) shows the activation associated with the verb-generation task (Figure 1). A map of the brain compares the score for predefined language regions of interest with a lead exposure index based on blood samples collected quarterly from birth to 5 years and at 5.5, 6, and 6.5 years (Figure 2). The result demonstrates that in one part of the brain, there is a significant inverse correlation with the mean childhood lead level (R = -0.39, p = 0.01) while in another part of the brain, researchers saw a strong positive correlation with the mean childhood lead level (R = 0.35, p = 0.03) (Yuan et al 2006).
Figure 1. Composite fMRI Activation Map for the Verb-Generation Task (N = 43). The left hemisphere (image right side) demonstrates activation in the dorsolateral prefrontal cortex, Broca’s, and Wernicke’s areas with overall left-sided dominance (Yuan et al 2006).
Figure 2. R-Map. Z-score compared to childhood mean blood lead levels. In Broca’s area, a negative correlation to childhood blood lead level is shown in blue. In the homolog of Wernicke’s area, a (+) correlation to childhood blood lead level is shown in yellow and red (Yuan et al 2006).
This study indicates that childhood lead exposure can have a significant and persistent impact on brain reorganization associated with language function. This is the first study to localize regions of the brain affected by lead exposure using fMRI and serves as a model for examining other adverse CNS effects of metals exposure. This is also among the first prospective studies using biomarkers of exposure in childhood to an environmental toxicant with disease or disability in adults (Yuan et al 2006).
The Cincinnati Children’s Center has been at the forefront of research implicating low-level exposure to environmental toxicants on intellectual and behavioral functions of children, including lead exposure at blood lead levels below 10 mg/dL and ETS exposure. These studies have led national and international agencies to re-examine the action levels set for lead exposure and raised questions about adverse consequences of low-level exposure to a variety of environmental chemicals (Canfield et al 2003, Lanphear et al 2005, Yolton et al 2005, Braun et al 2006).Braun JM, Kahn RS, Froehlich T, Auinger P, Lanphear BP4 2006. Exposures to environmental toxicants and attention deficit hyperactivity disorder in U.S. children. Environ Health Perspect. 2006 Dec;114(12):1904-9.
Canfield
RL, Henderson CR Jr, Cory-Slechta DA, Cox C, Jusko TA, Lanphear
BP 2003. Intellectual impairment in children with blood
lead concentrations below 10 microg per deciliter. N Engl
J Med. 2003 Apr 17;348(16):1517-26. Comment in: J Pediatr.
2003 Nov;143(5):687-8. N Engl J Med. 2003 Apr 17;348(16):1515-6. N
Engl J Med. 2003 Jul 31;349(5):500-2; author reply 500-2. N
Engl J Med. 2003 Jul 31;349(5):500-2; author reply 500-2. N
Engl J Med. 2003 Jul 31;349(5):500-2; author reply 500-2.
Froehlich T, Lanphear BP, Dietrich KN, Cory-Slechta D, Want N,
Kahn RS [in press]. ADHD-related
Executive Function: Interactions of the DRD4 Polymorphism, Lead, and Sex. Biological
Psychiatry, in press.
Kahn RS, Khoury J, Nichols WC, Lanphear BP 2003. Role of dopamine transporter genotype and maternal prenatal smoking in childhood hyperactive-impulsive, inattentive, and oppositional behaviors. J Pediatr. 2003 Jul;143(1):104-10.
Lanphear BP, Paulson J, Beirne S 2006. Trials and tribulations of protecting children from environmental hazards. Environ Health Perspect. 2006 Oct;114(10):1609-12.
Lanphear BP, Hornung R, Khoury J, Yolton K, Baghurst P, Bellinger DC, Canfield RL, Dietrich KN, Bornschein R, Greene T, Rothenberg SJ, Needleman HL, Schnaas L, Wasserman G, Graziano J, Roberts R 2005. Low-level environmental lead exposure and children's intellectual function: an international pooled analysis. Environ Health Perspect. 2005 Jul;113(7):894-9. Comment in: Environ Health Perspect. 2006 Feb;114(2):A85-6; author reply A86-7.
Yolton K, Dietrich K, Auinger P, Lanphear BP, Hornung R 2005. Exposure to environmental tobacco smoke and cognitive abilities among U.S. children and adolescents. Environ Health Perspect. 2005 Jan;113(1):98-103. Comment in: Environ Health Perspect. 2005 May;113(5):A296.
Yuan W, Holland SK, Cecil KM, Dietrich KN, Wessel SD, Altaye M, Hornung RW, Ris MD, Egelhoff JC, Lanphear BP 2006. The impact of early childhood lead exposure on brain organization: a functional magnetic resonance imaging study of language function. Pediatrics. 2006 Sep;118(3):971-7.
Full List of Publications | Publications List from NIEHS PubMed Database
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