Person: White, Roberta
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White
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Roberta
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White, Roberta
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Publication Benchmark dose calculations of methylmercury-associated neurobehavioural deficits(Elsevier BV, 2000) Budtz-Jørgensen, Esben; Grandjean, Philippe; Keiding, Niels; White, Roberta; Weihe, PalPrenatal methylmercury exposure is associated with neuropsychological deficits in Faroese children at age 7 years. Lower confidence bounds of benchmark doses (BMDLs) have now been calculated. With the cord-blood mercury concentration as the dose parameter, a logarithmic dose-response model tended to show a better fit than a linear dose model for the attention, language and verbal memory tests. The lowest BMDLs averaged ≈5 μg/l cord blood, which corresponds to a maternal hair concentration of ≈1 μg/g. However, most BMDLs for hair mercury concentrations were higher. Thus, the results of the benchmark calculations depend on the assumed dose-response model.Publication Functional MRI approach to developmental methylmercury and polychlorinated biphenyl neurotoxicity(Elsevier BV, 2011) White, Roberta; Palumbo, Carole L.; Yurgelun-Todd, Deborah; Heaton, Kristin J.; Weihe, Pal; Debes, Frodi; Grandjean, PhilippePrenatal and early childhood exposure to methylmercury (MeHg) or polychlorinated biphenyls (PCBs) are associated with deficits in cognitive, sensory, motor and other functions measured by neurobehavioral tests. The main objective of this pilot study was to determine whether functional magnetic resonance imaging (fMRI) is effective for visualization of brain function alterations related to neurobehavior in subjects with high prenatal exposure to the two neurotoxicants, MeHg and PCBs. Twelve adolescents (all boys) from a Faroese birth cohort assembled in 1986–1987 were recruited based on their prenatal exposures to MeHg and PCB. All underwent fMRI scanning during behavioral tasks at age 15 years. Subjects with high mixed exposure to MeHg and PCBs were compared to those with low mixed exposure on fMRI photic stimulation and a motor task. Boys with low mixed exposures showed patterns of fMRI activation during visual and motor tasks that are typical of normal control subjects. However, those with high exposures showed activation in more areas of the brain and different and wider patterns of activation than the low mixed exposure group. The brain activation patterns observed in association with increased exposures to MeHg and PCBs are meaningful in regard to the known neurotoxicity of these substances. This methodology therefore has potential utility in visualizing structural neural system determinants of exposure-induced neurobehavioral dysfunction.Publication Neuropsychological characteristics of Gulf War illness: A meta-analysis(Public Library of Science, 2017) Janulewicz, Patricia A.; Krengel, Maxine H.; Maule, Alexis; White, Roberta; Cirillo, Joanna; Sisson, Emily; Heeren, Timothy; Sullivan, KimberlyObjective: Gulf War illness (GWI) is a disorder related to military service in the 1991 GW. Prominent symptoms include fatigue, pain and cognitive problems. These symptoms were reported by GW Veterans (GWV) immediately after the war and were eventually incorporated into case definitions of GWI. Neuropsychological function in GW veterans has been studied both among deployed GWV and in GWV diagnosed with GWI. Results have been inconsistent between and across GW populations. The purpose of the present investigation was to better characterize neuropsychological function in this veteran population. Methods: Meta-analysis techniques were applied to published studies on neuropsychological performance in GWV to identify domains of dysfunction in deployed vs. non-deployed GW-era veterans and symptomatic vs. non-symptomatic GWVs. Results: Significantly decreased performance was found in three functional domains: attention and executive function, visuospatial skills and learning/memory. Conclusions: These findings document the cognitive decrements associated with GW service, validate current GWI case definitions using cognitive criteria, and identify test measures for use in GWI research assessing GWI treatment trial efficacy.Publication Methylmercury neurotoxicity independent of PCB exposure(National Institute of Environmental Health Sciences, 1999) Budtz-Jørgensen, E; Keiding, N; Grandjean, Philippe; White, RobertaPublication Cognitive deficits and magnetic resonance spectroscopy in adult monozygotic twins with lead poisoning.(2004) Weisskopf, Marc; Hu, Howard; Mulkern, Robert; White, Roberta; Aro, Antonio; Oliveira, Steven; Wright, RobertSeventy-one-year-old identical twin brothers with chronic lead poisoning were identified from an occupational medicine clinic roster. Both were retired painters, but one brother (J.G.) primarily removed paint and had a history of higher chronic lead exposure. Patella and tibia bone lead concentrations measured by K-X-ray fluorescence in each brother were 5-10 times those of the general population and about 2.5 times higher in J.G. than in his brother (E.G.). Magnetic resonance spectroscopy (MRS) studies examined N-acetylaspartate:creatine ratios, a marker of neuronal density. Ratios were lower in J.G. than in his brother. Scores on neurocognitive tests that assess working memory/executive function were below expectation in both twins. Short-term memory function was dramatically worse in J.G. than in his brother. These results demonstrate some of the more subtle long-term neurologic effects of chronic lead poisoning in adults. In particular, they suggest the presence of frontal lobe dysfunction in both twins, but more dramatic hippocampal dysfunction in the brother with higher lead exposure. The MRS findings are consistent with the hypothesis that chronic lead exposure caused neuronal loss, which may contribute to the impairment in cognitive function. Although a causal relation cannot be inferred, the brothers were genetically identical, with similar life experiences. Although these results are promising, further study is necessary to determine whether MRS findings correlate both with markers of lead exposure and tests of cognitive function. Nevertheless, the results point to the potential utility of MRS in determining mechanisms of neurotoxicity not only for lead but also for other neurotoxicants as well.Publication Neurobehavioral performance of Inuit children with increased prenatal exposure to methylmercury(Taylor & Francis Open, 2002) Weihe, Pal; Hansen, Jens C.; Murata, Katsuyuki; Debes, Frodi; Jorgensen, Poul J.; Steuerwald, Ulrike; White, Roberta; Grandjean, PhilippeExposure to methylmercury from marine mammals and other seafood may affect the development of the central nervous system. In a traditional Inuit community in Qaanaaq, Greenland, mercury concentrations in cord blood and maternal hair have been examined in connection with all births. We examined 43 children at age 7–12 years with a battery of neurobehavioral tests. The average mercury concentration in hair was 5.0 μ/g and 1.5 μ/g in children and mothers, respectively. Clinical neurological examination did not reveal any obvious deficits. However, neuropsychological tests showed possible exposure-associated deficits, though only in a few cases reaching statistical significance. In conjunction with data from other studies, peak latencies on brainstem auditory evoked potentials tended to be prolonged at increased exposure levels. The data from the present study therefore appears in accordance with other evidence that prenatal or early postnatal exposures to methylmercury may cause subtle neurobehavioral deficits.Publication Impact of prenatal methylmercury exposure on neurobehavioral function at age 14 years(Elsevier BV, 2006) Debes, Frodi; Budtz-Jørgensen, Esben; Weihe, Pal; White, Roberta; Grandjean, PhilippeA cohort of 1022 consecutive singleton births was generated during 1987–1988 in the Faroe Islands, where increased methylmercury exposure occurs from traditional seafood diets that include pilot whale meat. The prenatal exposure level was determined from mercury analyses of cord blood, cord tissue, and maternal hair. At age 14 years, 878 of 1010 living cohort members underwent detailed neurobehavioral examination. Eighteen participants with neurological disorders were excluded. Blood and hair samples obtained from the participants were analyzed for mercury. The neuropsychological test battery was designed based on the same criteria as applied at the examination at age 7 years. Multiple regression analysis was carried out and included adjustment for confounders. Indicators of prenatal methylmercury exposure were significantly associated with deficits in finger tapping speed, reaction time on a continued performance task, and cued naming. Postnatal methylmercury exposure had no discernible effect. These findings are similar to those obtained at age 7 years, and the relative contribution of mercury exposure to the predictive power of the multiple regression models was also similar. An analysis of the test score difference between results at 7 and 14 years suggested that mercury-associated deficits had not changed between the two examinations. In structural equation model analyses, the neuropsychological tests were separated into five groups; methylmercury exposure was significantly associated with deficits in motor, attention, and verbal tests. These findings are supported by independent assessment of neurophysiological outcomes. The effects on brain function associated with prenatal methylmercury exposure therefore appear to be multi-focal and permanent.Publication Neurotoxic Risk Caused by Stable and Variable Exposure to Methylmercury From Seafood(Elsevier, 2003) Grandjean, Philippe; White, Roberta; Weihe, Pal; Jørgensen, Poul J.Objectives.—To examine whether the dose-effect relationship for developmental mercury neurotoxicity is affected by variable mercury exposure during pregnancy. Methods.—The study was based on a birth cohort of 1022 children born in the Faroe Islands between March 1986 and December 1987. Neurobehavioral performance of 917 children (90%) was assessed at age 7. Intrauterine methylmercury exposure was determined from mercury concentrations in cord blood and 2 sets of maternal hair. Complete exposure information was available for 614 children (67%). Results.—In children with complete exposure data, 8 of 16 neuropsychological tests showed deficits significantly associated with the cord-blood mercury concentration after confounder adjustment. Variable intrauterine exposure was suggested by disagreement between mercury concentrations in the 2 maternal hair samples. Removal of the 61 children (10%) with the greatest degree of variable exposure had a minimal effect on most exposure-effect relationships. However, the effect of the cord-blood concentration on verbal learning and memory was greater after this exclusion. Conclusion.—The study supports previous findings from this cohort study that maternal mercury exposure during pregnancy is associated with neuropsychological deficits detectable at age 7 years and that this association is evident in women with stable exposures throughout pregnancy. Thus the association is not the result of variable exposures.Publication Consequences of exposure measurement error for confounder identification in environmental epidemiology(Wiley-Blackwell, 2003) Budtz-Jørgensen, Esben; Keiding, Niels; Grandjean, Philippe; Weihe, Pal; White, RobertaNon-differential measurement error in the exposure variable is known to attenuate the dose–response relationship. The amount of attenuation introduced in a given situation is not only a function of the precision of the exposure measurement but also depends on the conditional variance of the true exposure given the other independent variables. In addition, confounder effects may also be affected by the exposure measurement error. These difficulties in statistical model development are illustrated by examples from a epidemiological study performed in the Faroe Islands to investigate the adverse health effects of prenatal mercury exposure.