Lead, Genes, And Cognition In Underserved Children
Christina Sobin, Clinical Director
Psychologyuniversity Of Texas El Paso
Grant 1R21HD060120-01 from Eunice Kennedy Shriver National Institute Of Child Health & Human Development IRG: DBD
Abstract: The goal of this work is to begin to identify biological mechanisms that contribute to neurocognitive deficits in children exposed to low-level lead. This research plan proposes to measure blood lead levels in a large population of minority and underserved children; compare neurocognitive functioning in children with and without detectable blood lead levels; and examine associations between selected genetic polymorphisms and neurocognitive performance in children exposed to low-level lead. Lead exposure is a significant health disparity. Low-level lead exposure has long been associated with diminished cognitive function, and may pose an unrecognized threat to the cognitive health and well-being of an unknown number of minority and underserved children. Moreover, previously unexamined common genetic differences may potentiate the neurotoxic effects of lead in children. Lead toxicity is diagnosed when a child´s blood lead level (BLL) is > 10 micrograms per deciliter (g/dL). According to the EPA however, a "Reference Dose" value, that is a concentration below which no adverse effects have been observed, is not available for lead. In response to over 40 studies showing diminished IQ in children with BLLs < 10 g/dL, the CDC convened an expert committee in 2003 to critically examine the findings. The findings were unequivocally confirmed. But in its decision to maintain the 10 g/dL threshold, the committee cited the need for studies suggesting causative biological mechanisms. We do not yet understand the mechanisms by which low-level lead exposure causes neurocognitive decline in young children. This is a critical knowledge gap, which creates the risk of lower cognitive function and diminished quality of life, especially for minority and underserved children. As a result of this gap, child blood lead levels < 10.0 g/dL are ignored. Our central hypothesis is that chronic low-level lead exposure impairs neurocognitive function through mechanisms that are genetically mediated. H1 25% of minority children between the ages of 5 and 12 have "detectable" blood lead levels (4.0 - 9.9 g/dL); H2 as compared to children with "undetectable" blood lead levels, children with "detectable" blood lead levels perform more poorly on neurocognitive tasks associated with brain networks specifically vulnerable to lead; H3 children with "detectable" blood lead levels, and carrying one or both genetic polymorphisms, have lowest scores on tests of neurocognitive function. Findings from these studies may begin to suggest the numbers of minority and underserved children ages 5 - 12 currently exposed to low-level lead; which types of neurocognitive deficits result; and whether common genetic differences potentiate the neurotoxic effects of lead. The findings may also suggest new avenues for detection, primary prevention and intervention. Lead exposure is a significant health disparity, low-level lead exposure has been associated with diminished cognitive function, and yet low-level lead exposure continues to be ignored, perhaps posing a hidden threat to the health and well-being of an unknown number of minority and underserved children. Common genetic differences may increase its neurotoxic effects. Findings from these studies may begin to suggest the numbers of currently exposed minority and underserved children ages 5 - 12 years, and which neurocognitive deficits result, while suggesting new avenues for detection and primary prevention
Project start date: 2009-04-09
Project end date: 2011-02-28
Sponsored Links Excellgen http://Excellgen.com
Grants awarded to Christina Sobin
LEAD, GENES, AND COGNITION IN UNDERSERVED CHILDREN
Christina Sobin, Associate Professor
University Of Texas El Paso, El Paso, Tx 79968
Grant 5R21HD060120-02 from Eunice Kennedy Shriver National Institute Of Child Health & Human Development
Abstract: The goal of this work is to begin to identify biological mechanisms that contribute to neurocognitive deficits in children exposed to low-level lead. This research plan proposes to measure blood lead levels in a large population of minority and underserved children; compare neurocognitive functioning in children with and without detectable blood lead levels; and examine associations between selected genetic polymorphisms and neurocognitive performance in children exposed to low-level lead. Lead exposure is a significant health disparity. Low-level lead exposure has long been associated with diminished cognitive function, and may pose an unrecognized threat to the cognitive health and well-being of an unknown number of minority and underserved children. Moreover, previously unexamined common genetic differences may potentiate the neurotoxic effects of lead in children. Lead toxicity is diagnosed when a child´s blood lead level (BLL) is > 10 micrograms per deciliter (g/dL). According to the EPA however, a "Reference Dose" value, that is a concentration below which no adverse effects have been observed, is not available for lead. In response to over 40 studies showing diminished IQ in children with BLLs < 10 g/dL, the CDC convened an expert committee in 2003 to critically examine the findings. The findings were unequivocally confirmed. But in its decision to maintain the 10 g/dL threshold, the committee cited the need for studies suggesting causative biological mechanisms. We do not yet understand the mechanisms by which low-level lead exposure causes neurocognitive decline in young children. This is a critical knowledge gap, which creates the risk of lower cognitive function and diminished quality of life, especially for minority and underserved children. As a result of this gap, child blood lead levels < 10.0 g/dL are ignored. Our central hypothesis is that chronic low-level lead exposure impairs neurocognitive function through mechanisms that are genetically mediated. H1 25% of minority children between the ages of 5 and 12 have "detectable" blood lead levels (4.0 - 9.9 g/dL); H2 as compared to children with "undetectable" blood lead levels, children with "detectable" blood lead levels perform more poorly on neurocognitive tasks associated with brain networks specifically vulnerable to lead; H3 children with "detectable" blood lead levels, and carrying one or both genetic polymorphisms, have lowest scores on tests of neurocognitive function. Findings from these studies may begin to suggest the numbers of minority and underserved children ages 5 - 12 currently exposed to low-level lead; which types of neurocognitive deficits result; and whether common genetic differences potentiate the neurotoxic effects of lead. The findings may also suggest new avenues for detection, primary prevention and intervention. Lead exposure is a significant health disparity, low-level lead exposure has been associated with diminished cognitive function, and yet low-level lead exposure continues to be ignored, perhaps posing a hidden threat to the health and well-being of an unknown number of minority and underserved children. Common genetic differences may increase its neurotoxic effects. Findings from these studies may begin to suggest the numbers of currently exposed minority and underserved children ages 5 - 12 years, and which neurocognitive deficits result, while suggesting new avenues for detection and primary prevention
Keywords: 0-11 years old; 12 year old; 5-ALA; 5-Amino-4-oxopentanoic Acid; 5-Aminolevulinic Acid; Adverse effects; Affect; Age; Amino-Levulinic Acid; Aminolevulinic Acid; Animal Behavior; Animals; Award; Behavior; Behavior, Animal; Behavioral Genetics; Biological; Brain; CDC; Centers for Disease Control; Centers for Disease Control (U.S.); Centers for Disease Control and Prevention; Centers for Disease Control and Prevention (U.S.); Child; Child Behavior; Child Youth; Children (0-21); Chronic; Clinical; Cognition; Cognitive; Cognitive Disturbance; Cognitive Impairment; Cognitive decline; Cognitive function abnormal; Data; Delta-Aminolevulinic Acid; Detection; Development; Diagnosis; Disturbance in cognition; Dose; Encephalon; Encephalons; Exposure to; Frequencies (time pattern); Frequency; Future; Genes; Genetic; Genetic Determinants of Behavior; Genetic Models; Genetic Polymorphism; Genetics, Behavioral; Goals; Health; Human, Child; IQ Deficit; Impaired cognition; Knowledge; Laboratories; Lead; Lead Poisoning; Link; Measurement; Measures; Mediating; Methods; Minority; Models, Genetic; Nervous System, Brain; Neurocognitive; Neurocognitive Deficit; Neuromediator Receptors; Neuroregulator Receptors; Neurotransmitter Receptor; Outcome; Pb element; Pb exposed; Pb exposure; Pb lead toxicity; Pb poisoning; Pb toxic effect; Pb2+ Toxicity; Pb2+ lead toxicity; Pb2+ poisoning; Pb2+ toxic effect; Pentanoic acid, 5-amino-4-oxo-; Performance; Personal Satisfaction; Polymorphism (Genetics); Polymorphism, Genetic; Population; Preventive Intervention; Primary Prevention; QOL; Quality of life; Receptors, Neurohumor; Research; Risk; Sampling; School-Age Population; Schools; Screening procedure; Severities; Technology; Treatment Side Effects; Underrepresented Minority; United States Centers for Disease Control; United States Centers for Disease Control and Prevention; Work; base; behavior genetics; blood Pb; blood lead; brain cell; children; cognitive dysfunction; cognitive function; cognitive loss; cognitively impaired; d-Amino-Levulinic Acid; design; designing; experience; exposed to lead; exposure to lead; health disparities; health disparity; heavy metal Pb; heavy metal lead; lead exposed; lead exposure; lead toxic effect; lead toxicity; neurocognitive test; neurotoxic; new approaches; new technology; novel; novel approaches; novel strategies; novel strategy; plumbism; polymorphism; population based; preventional intervention strategy; public health relevance; receptor function; response; school age; screening; screenings; side effect; therapy adverse effect; toxic effect to lead; toxicity to lead; treatment adverse effect; twelve year old; under-represented minority; underserved minority; well-being; youngster
Relevance: RELEVANCE Lead exposure is a significant health disparity, low-level lead exposure has been associated with diminished cognitive function, and yet low-level lead exposure continues to be ignored, perhaps posing a hidden threat to the health and well-being of an unknown number of minority and underserved children. Common genetic differences may increase its neurotoxic effects. Findings from these studies may begin to suggest the numbers of currently exposed minority and underserved children ages 5 - 12 years, and which neurocognitive deficits result, while suggesting new avenues for detection and primary prevention
Project start date: 2009-04-09
Project end date: 2011-02-28
Budget start date: 1-MAR-2010
Budget end date: 28-FEB-2011
PFA/PA: PA-07-391
5R21HD060120-02 (2010): $183150
3R21HD060120-01S1 (2009): $82546