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Childhood lead exposure has devastating lifelong consequences, as even low-level exposure stunts intelligence and leads to delinquent behavior. However, these consequences may be more extensive than previously thought because childhood lead exposure may adversely affect normal-range personality traits. Personality influences nearly every aspect of human functioning, from well-being to career earnings to longevity, so effects of lead exposure on personality would have far-reaching societal consequences. In a preregistered investigation, we tested this hypothesis by linking historic atmospheric lead data from 269 US counties and 37 European nations to personality questionnaire data from over 1.5 million people who grew up in these areas. Adjusting for age and socioeconomic status, US adults who grew up in counties with higher atmospheric lead levels had less adaptive personality profiles: they were less agreeable and conscientious and, among younger participants, more neurotic. Next, we utilized a natural experiment, the removal of leaded gasoline because of the 1970 Clean Air Act, to test whether lead exposure caused these personality differences. Participants born after atmospheric lead levels began to decline in their county had more mature, psychologically healthy adult personalities (higher agreeableness and conscientiousness and lower neuroticism), but these findings were not discriminable from pure cohort effects. Finally, we replicated associations in Europeans. European participants who spent their childhood in areas with more atmospheric lead were less agreeable and more neurotic in adulthood. Our findings suggest that further reduction of lead exposure is a critical public health issue., Competing Interests: The authors declare no competing interest.

Lead (Pb) is a neurotoxic heavy metal pollutant. Despite the efforts to reduce Pb environmental exposure and to prevent Pb poisoning, exposure in human populations persists. Studies of adults with history of childhood lead exposure have consistently demonstrated cognitive impairments that have been associated with sustained glutamate signaling. Additionally, some clinical studies have also found correlations between Pb exposure and increased proclivity to drug addiction. Thus, here we sought to investigate if developmental Pb exposure can increase propensity to alcohol consumption and relapse using an alcohol self-administration paradigm. Because Pb exposure is associated with increased glutamatergic tone, we also studied the effects on the expression of synaptic and non-synaptic glutamate transporters in brain regions associated with drug addiction such as the nucleus accumbens (NAc), dorsomedial striatum (DMS), dorsolateral striatum (DLS), and medial prefrontal cortex (mPFC). We found that while developmental Pb exposure did not increase risk for alcohol self-administration, it did play a role in relapsing to alcohol. The effects were associated with differential expression of the glutamate transporter 1 (GLT1) and the glutamate/cystine antiporter (xCT). In the NAc and DLS the expression of GLT1 was found to be significantly reduced, while no changes were found in DMS or mPFC. Contrastingly, xCT was found to be upregulated in NAc but downregulated in DLS, with no changes in DMS or mPFC. Our data suggest that lead exposure is involved in relapse to alcohol seeking, an effect that could be associated with downregulation of GLT1 and xCT in the DLS., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: We sought to investigate the effects and mechanism of lead and a high-fat diet on cognitive function and the central nervous system in mice., Methods: Eighty-four healthy male mice were randomly divided into a control group (n = 21) (fed with common diet and free drinking), a lead exposure group (n = 21) (fed with common diet and 300 mg/L lead acetate solution), a high-fat group (n = 21) (fed with high-fat diet and free drinking), and a lead + high-fat group (n = 21) (fed with high-fat diet and 300 mg/L lead acetate solution). In 10 weeks after lead exposure, the mice of all groups were tested for the cognition, learning and memory abilities, body weight, serum triglyceride (TG), low-density lipoprotein, and high-density lipoprotein, as well as for the contents of lead, interleukin 6 (IL-6), interleukin 17 (IL-17), interferon γ, advanced glycation end products (AGEs), glutathione S-transferase (GSH-ST), and hydrogen peroxide in the brain tissues., Results: Compared with the control group and the lead-exposed group, the body weights of mice in the high-fat group and the lead + high-fat group increased significantly from the sixth week of the experiment, of which the difference was statistically significant (P < 0.05). Compared with the control group and the high-fat group, the lead content in brain tissue of the lead exposure group and the lead + high-fat group increased significantly, of which the difference was statistically significant (P < 0.05). Compared with the control group, the escape latent period, triglyceride, low-density lipoprotein, IL-6, IL-17, interferon γ, and AGEs of the remaining 3 groups increased significantly, but the recognition index, passing platform times, high-density lipoprotein, and GSH-ST significantly decreased (P < 0.05); the second and third escape latent periods, IL-6, IL-17, and AGEs of lead + high-fat group, were obviously higher than the remaining 3 groups, but the passing platform times were obviously lower than the remaining 3 groups, of which the difference was statistically significant. The content of hydrogen peroxide in brain tissues had no difference among groups (P > 0.05)., Conclusions: The lead and high-fat diet resulted in lipid metabolism disorders and impaired the cognitive function and central nervous system by promoting the secretion of inflammatory factors in glial cells, inducing the inflammatory reaction of brain tissue, inhibiting GSH-ST expression, and increasing AGEs content., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Even at low levels in blood, lead has been associated with reduced IQ scores, behavioural problems, learning impediments, aggression and violent behaviour. Since the 1980s, the South African Medical Research Council (SAMRC) has been investigating the sources of exposure to lead in South Africa (SA), the groups at highest risk of lead poisoning and a selection of the myriad associated health and social consequences. SAMRC research evidence contributed to the phasng out of leaded petrol, restrictions on lead in paint and other interventions. Subsequently, childhood blood lead levels in SA declined significantly. More recent studies have revealed elevated risks of lead exposure in subsistence fishing and mining communities, users of arms and ammunition, those ingesting certain traditional medicines, and users of certain ceramicware and artisanal cooking pots. Lead-related cognitive damage costs the SA economy ~USD17.7 (ZAR261.3) billion annually, justifying further SAMRC investment in lead exposure research in the country.

Chronic lead (Pb) exposure has been shown to reduce the expression of some synaptic proteins which are involved in vesicular trafficking and affect presynaptic neurotransmitter release. However, the precise mechanisms by Pb impairs neurotransmitter release are still not well defined. In the current study, we aimed to elucidate the changes of Huntingtin-associated protein 1 (HAP1) in Pb exposed rats and PC12 cells models and its molecular mechanism. Repressor element-1 silencing transcription (REST) modulates the expression of genes containing the repressor element 1 (RE-1) cis-regulatory DNA sequence. HAP1 promoter region contains a RE-1 binding motif. We also observed whether Pb exposure regulated the HAP1 transcription level through influencing the expression of REST. Mother rats were exposed to 0.5 and 2 g/L Pb acetate (PbAc) in drinking water from the first day of gestation until postnatal 21 days, then the offspring rats were continued to drink PbAc for 1 year, while the control groups received drinking water. PC12 cells were divided into 3 groups: 0 μM, 1 μM and 100 μM PbAc. The results revealed that Pb levels in blood and brain of Pb exposed groups were significantly higher than that of the control group. The ability of learning and memory in Pb exposed rats was decreased. Pb exposure reduced the expression of HAP1 and increased the REST expression. Silencing REST could reverse the decreasing of HAP1 in Pb exposed PC12 cells. Our findings raise a possibility that the decreasing of HAP1 expression by Pb exposure may affect neurotransmitter release and results in impairments in spatial learning and memory ability., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Although rates of violent crime have been on the decline in the United States for the past two decades, young people-and particularly young men-continue to commit and fall victim to alarmingly high rates of violence. Effective prevention requires data on what the determinants of violence are and when in the life course they emerge. The goal of this review was to identify early-in-life risk factors for violence and to describe (a) who is most affected and (b) effect mechanisms. I focus on abuse and neglect and exposure to lead as risk factors for violence that disproportionately affect young children and that are likely to have causal effects on development. I conclude with future directions for research and intervention., (© 2019 Michigan Association for Infant Mental Health.)

Objectives: The Flint Community Resilience Group (Flint, Michigan USA) and the Centers for Disease Control and Prevention (CDC; Atlanta, Georgia USA) assessed behavioral health concerns among community members to determine the impact of lead contamination of the Flint, Michigan water supply., Methods: A Community Assessment for Public Health Emergency Response (CASPER) was conducted from May 17 through May 19, 2016 using a multi-stage cluster sampling design to select households and individuals to interview., Results: One-half of households felt overlooked by decision makers. The majority of households self-reported that at least one member experienced more behavioral health concerns than usual. The prevalence of negative quality of life indicators and financial concerns in Flint was higher than previously reported in the Michigan 2012 and 2014 Behavioral Risk Factor Surveillance System (BRFSS) survey., Conclusions: The following can be considered to guide recovery efforts in Flint: identifying additional resources for behavioral health interventions and conducting follow-up behavioral health assessments to evaluate changes in behavioral health concerns over time; considering the impact of household economic factors when implementing behavioral health interventions; and ensuring community involvement and engagement in recovery efforts to ease community stress and anxiety. FortenberryGZ, ReynoldsP, BurrerSL, Johnson-LawrenceV, WangA, SchnallA, PullinsP, KieszakS, BayleyegnT, WolkinA. Assessment of behavioral health concerns in the community affected by the Flint water crisis - Michigan (USA) 2016. Prehosp Disaster Med. 2018;33(3):256-265.

Lead (Pb) is an environmental neurotoxic metal. Chronic exposure to Pb causes deficits of learning and memory in children and spatial learning deficits in developing rats. In this study we investigated the effects of Pb exposure on the expression of HMGB1 and HO-1 in rats and PC12 cells. The animals were randomly divided to three groups: control group; low lead exposure group; high lead exposure group; PC12 cells were divided into 3 groups: 0 μM (control group), 1 μM and 100 μM Pb acetate. The results showed that Pb levels in blood and brain of Pb exposed groups were significantly higher than that of the control group (p < 0.05). The expression of HMGB1 and HO-1 were increased in Pb exposed groups than that of the control group (p < 0.05). Moreover, we found that the up-regulation of HO-1 in Pb exposure environment inhibited the expression of HMGB1., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Exposure to lead is detrimental to children's development. YouTube is a form of social media through which people may learn about lead poisoning. The aim of this cross-sectional study was to analyze the variation in lead poisoning-related YouTube contents between different video sources. The 100 most viewed lead poisoning-related videos were manually coded, among which, 50 were consumer-generated, 19 were created by health care professionals, and 31 were news. The 100 videos had a total of more than 8.9 million views, with news videos accounting for 63% of those views. The odds of mentioning what lead poisoning is, how to remove lead, and specifically mentioning the danger in ages 1-5 because of rapid growth among videos created by health care professionals were 7.28 times (Odds ratio, OR = 7.28, 95% CI, 2.09, 25.37, p = 0.002); 6.83 times (OR = 6.83, 95% CI, 2.05, 22.75, p = 0.002) and 9.14 times (OR = 9.14, CI, 2.05, 40.70, p = 0.004) that of consumer-generated videos, respectively. In this study, professional videos had more accurate information regarding lead but their videos were less likely to be viewed compared to consumer-generated videos and news videos. If professional videos about lead poisoning can attract more viewers, more people would be better informed and could possibly influence policy agendas, thereby helping communities being affected by lead exposure.

Prior to the mid-1980s, suicide in Indigenous population in Northwestern Ontario, Canada, was rare, occurring at rates of 1-2 per year among over 20 communities. By the early 1990s, the completed suicide rates in the same communities were among the highest in the world. Prior to the outbreak of the suicide epidemic, sniffing of gasoline containing tetraethyl was common in many communities. Existing literature confirms that tetraethyl lead poisoning is associated with alterations to the amyloid-β protein precursor and amyloid-β as well as the 5-HT-1B receptor. The presence of this risk factor within the population warrants further inquiry., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

During the cocaine epidemic of the 1980s and early 1990s, many expressed fears that children with intrauterine cocaine exposure (IUCE) would grow up to be unusually violent. The present study examines the relationship of caregiver reports of school-age children's aggressive behavior with IUCE and postnatal exposure to violence. Respondents were 140 low-income, primarily African American children, ages 8-11, and each child's current primary caregiver from a longitudinal study evaluating potential long term sequelae of IUCE. Multiple regression analyses were used to investigate the independent and interactive effects of level of IUCE (None (n = 69), Lighter (n = 47), Heavier (n =  24)) and exposure to violence (Violence Exposure Scale for Children-Revised) on aggressive behavior (Child Behavior Checklist), while also controlling for other intrauterine substance exposures and additional contextual factors. Children's self-reported exposure to violence was significantly positively associated with caregivers' reports of aggressive behavior (β = 2.17, P = .05), as was concurrent caregiver's psychiatric distress (β = .15, P = .003). However, neither IUCE nor its interaction with exposure to violence showed a significant association with aggressive behavior. Findings suggest the importance of postnatal social environment rather than IUCE in predicting aggressive behavior in childhood., (© 2015 Wiley Periodicals, Inc.)

High levels of waterborne manganese have been associated with problematic behavior in school-aged children, however to date this has not been reported for children exposed to airborne manganese. The objective of the present study was to examine behavioral traits among children with exposure to airborne manganese from a ferro-manganese alloy plant, located in the metropolitan region of Salvador, Brazil. The study included 34 boys and 36 girls, aged 7-12 years, living in two communities within a 3-km radius from the plant. For each child, hair manganese levels (MnH) and blood lead (PbB) levels were analyzed by graphite furnace atomic absorption spectrometry. The Children's Behavior Check List (CBCL) (Portuguese version validated in Brazil) was administered to parents or caregivers, providing scale scores of internalizing (withdrawn, somatic complaints, and anxious/depressed scales), externalizing (disruptive and aggressive) behaviors and a separate scale for attention problems. Median and range for MnH and PbB were 11.48 μg/g (range: 0.52-55.74); 1.1 μg/dL (range: 0.5-6.1), respectively. Spearman correlation analyses showed that several behavioral indices were significantly correlated with MnH levels for girls, but not for boys: total externalizing behavior (rho=0.484 vs rho=0.041) and attention problem scores (rho=0.542 vs rho=0.003) coefficients were significantly at p<0.001 level, respectively for girls and boys. No significant correlation was observed with any of the internalizing sub-scales. A linear regression model was fitted with the total externalizing behavior, inattention and total CBCL scores as dependent variables, with log transformed MnH stratified by sex, adjusting for age and maternal IQ. Total externalizing behaviors and attention problem scores were significantly associated with girls' MnH levels but not with boys'. Adjusting for maternal IQ, the β-coefficients for LogMnH associations with total externalizing and attention problems are 8.85 (95%CI 2.44-15.24) and 4.03 (95%CI 1.50-6.56) for girls. For boys, after adjusting for age, the β-coefficients are 0.08 (95%CI 11.51-11.66) and -0.05 (95%CI 4.34-4.25), respectively. The findings of this study suggest a positive association between elevated Mn exposure and externalizing behavioral problems and inattention, with girls presenting more pronounced effects. Future studies on Mn exposure in children should attempt to further elucidate sex and/or gender differences in Mn exposed populations., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Residents of Herculaneum, Missouri have been influential in shaping the management of contamination challenges resulting from the community's proximity to the last primary lead processing plant in the United States. This paper provides a nuanced examination of two perspectives of resident activist groups involved in lead-related controversy in Herculaneum. Ethnographic data collection and storyline analysis were used to trace the evolution in local views from resembling an industrialist-environmentalist dichotomy to more compromising positions associated with ecological modernization. Implications for characterizing public environmental perspectives in the US as beginning to entertain certain aspects of the ecological modernist paradigm are discussed., (© The Author(s) 2013.)

Background: It is well known that lead exposure induces neurotoxic effects, which can result in a variety of neurocognitive dysfunction. Especially, occupational lead exposures in adults are associated with decreases in cognitive performance including working memory. Despite recent advances in human neuroimaging techniques, the neural correlates of lead-exposed cognitive impairment remain unclear. Therefore, this study was aimed to compare the neural activations in relation to working memory function between the lead-exposed subjects and healthy controls., Methodology/principal Findings: Thirty-one lead-exposed subjects and 34 healthy subjects performed an n-back memory task during MRI scan. We performed fMRI using the 1-back and 2-back memory tasks differing in cognitive demand. Functional MRI data were analyzed using within- and between-group analysis. We found that the lead-exposed subjects showed poorer working memory performance during high memory loading task than the healthy subjects. In addition, between-group analyses revealed that the lead-exposed subjects showed reduced activation in the dorsolateral prefrontal cortex, ventrolateral prefrontal cortex, pre supplementary motor areas, and inferior parietal cortex., Conclusions/significance: Our findings suggest that functional abnormalities in the frontoparietal working memory network might contribute to impairments in maintenance and manipulation of working memory in the lead-exposed subjects.

Appropriate selection and measurement of lead biomarkers of exposure are critically important for health care management purposes, public health decision making, and primary prevention synthesis. Lead is one of the neurotoxicants that seems to be involved in the etiology of psychologies. Biomarkers are generally classified into three groups: biomarkers of exposure, effect, and susceptibility.The main body compartments that store lead are the blood, soft tissues, and bone; the half-life of lead in these tissues is measured in weeks for blood, months for soft tissues, and years for bone. Within the brain, lead-induced damage in the prefrontal cerebral cortex, hippocampus, and cerebellum can lead to a variety of neurological disorders, such as brain damage, mental retardation, behavioral problems, nerve damage, and possibly Alzheimer's disease, Parkinsons disease, and schizophrenia. This paper presents an overview of biomarkers of lead exposure and discusses the neurotoxic effects of lead with regard to children and adults.

Background: Lead is a heavy metal and important environmental toxicant and nerve poison that can destruction many functions of the nervous system. Lead poisoning is a medical condition caused by increased levels of lead in the body. Lead interferes with a variety of body processes and is toxic to many organs and issues, including the central nervous system. It interferes with the development of the nervous system, and is therefore particularly toxic to children, causing potentially permanent neural and cognitive impairments. In this study, we investigated the relationship between lead poisoning and the intellectual and neurobehavioral capabilities of children., Methods: The background characteristics of the research subjects were collected by questionnaire survey. Blood lead levels were detected by differential potentiometric stripping analysis (DPSA). Intelligence was assessed using the Gesell Developmental Scale. The Achenbach Child Behavior Checklist (CBCL) was used to evaluate each child's behavior., Results: Blood lead levels were significantly negatively correlated with the developmental quotients of adaptive behavior, gross motor performance, fine motor performance, language development, and individual social behavior (P < 0.01). Compared with healthy children, more children with lead poisoning had abnormal behaviors, especially social withdrawal, depression, and atypical body movements, aggressions and destruction., Conclusion: Lead poisoning has adverse effects on the behavior and mental development of 2-4-year-old children, prescribing positive and effective precautionary measures.

More than 90% of body lead is stored in bone. The technique of K-X-Ray fluorescence developed in the 1990s has enabled the quantitative measurement of decades of cumulative lead in bone, whereas blood lead levels reflect only recent exposure to lead. Bone lead is mobilized into the blood like bone calcium, as in osteoporosis, and exposes the patient to increased lead load. Many studies have assessed the toxic effect of chronic exposure from childhood to old age in present or former workers in industrial lead, as well as in non-occupational citizens in whom social and environmental circumstances might have induced higher exposure levels. This review points to the effects of elevated levels of bone lead and the associated cognitive decline among the elderly, with lead toxicity being one of the possible causes of degenerative dementia. There is evidence of an association between increased bone lead levels and renal disease, degenerative diseases like cataract, and suggestive but not causal association with blood pressure and hypertension. Community surveys show increased mortality associated with exposure to lead. Removal of sources of lead exposure, for example the use of non-leaded petrol, has reduced lead levels in the population, and there are currently strong recommendations to further lower the present allowed blood lead level to minimize chronic cumulative lead toxicity.

The relationship between the blood lead concentration and cognitive function in children and adults with different ALAD genotypes who participated in the third National Health and Nutrition Examination Survey was investigated. The relationship between blood lead and serum homocysteine concentrations was also investigated. In children 12 to 16 years old, no difference in the relationship between cognitive function and blood lead concentration between genotypes was found. In adults 20 to 59 years old, mean reaction time decreased as the blood lead concentration increased in the ALAD rs1800435 CC/CG group. This represents an improvement in performance. In adults 60 years and older, no difference in the relationship between cognitive function and blood lead concentration between genotypes was found. The serum homocysteine concentration increased as the blood lead concentration increased in adults 20 to 59 years old and 60 years and older, but there were no differences between genotypes. The mean blood lead concentration of children with the ALAD rs1800435 CC/CG genotype was less than that of children with the GG genotype.

Objective: The authors recently reported that blood lead (Pb) was a significant mediator for the positive association between socioeconomic status (SES) and peripheral vascular responses to acute stress in children (B. B. Gump et al., 2007). The present study considers the possibility that Pb may also mediate an association between SES and cortisol responses to acute stress., Design: Early childhood Pb exposure was tested as a mediator for cross-sectional associations between SES and cortisol responses., Main Outcome Measures: The primary outcome was cortisol responses to acute stress in 9.5-year-old children (N = 108)., Results: Lower family income was associated with significantly greater cortisol levels following an acute stress task. A mediational analysis confirmed that Pb was a significant mediator for this association., Conclusion: These results reaffirm the importance of considering the chemical environment as well as social and psychological environment when evaluating psychophysiological effects of low SES., (Copyright 2009 APA, all rights reserved.)

Lead-induced neurotoxicity acquired by low-level long-term exposure has special relevance for children. A plethora of recent reports has demonstrated a direct link between low-level lead exposure and deficits in the neurobehavioral-cognitive performance manifested from childhood through adolescence. In many studies, aggressiveness and delinquency have also been suggested as symptoms of lead poisoning. Several environmental, occupational and domestic sources of contaminant lead and consequent health risks are largely identified and understood, but the occurrences of lead poisoning remain numerous. There is an urgent need for public health policies to prevent lead poisoning so as to reduce individual and societal damages and losses. In this paper we describe unsuspected sources of contaminant lead, discuss the economic losses and urban violence possibly associated with lead contamination and review the molecular basis of lead-induced neurotoxicity, emphasizing its effects on the social behavior, delinquency and IQ of children and adolescents.

Background: We carried out animal experiments based on the orthogonal design L(8)(2(7)) setting seven factors with two different levels of each and 10 groups of rats. The nutrients tested were tyrosine, glycine, methionine, taurine, ascorbic acid, thiamine and zinc., Objectives: The objective of this study was to explore the optimal combinations of nutrients for prevention or amelioration of lead-induced learning and memory impairment., Methods: Rats were supplemented with nutrients by gavage once a day in two experiments: one was simultaneous nutrient supplementation with lead acetate administration (800 mg l(-1)) for 8 weeks (prophylactic supplementation) and the other was nutrient supplementation for 4 weeks after the cessation of 4 weeks of lead administration (remedial supplementation). Morris water maze was initiated at ninth week. Rats were terminated for assays of levels of Pb in blood, activities of superoxide dismutase (SOD) and nitric oxide synthase (NOS) in hippocampus, levels of nitric oxide (NO) in hippocampus and expressions of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and cyclic adenosine monophosphate (cAMP) response element-binding protein messenger RNA in hippocampus., Results: Results showed that in prophylactic supplementation, methionine, taurine, zinc, ascorbic acid and glycine were the effective preventive factors for decreasing prolonged escape latency, increasing SOD and NOS activities and NO levels in the hippocampus, respectively. On the other hand, in remedial supplementation, taurine was the effective factor for reversing Pb-induced decrease in activities of SOD, NOS and levels of NO., Conclusions: In conclusion, the optimum combinations of nutrients appear to be methionine, taurine, zinc, ascorbic acid and glycine for the prevention of learning and memory impairment, while taurine and thiamine appear to be the effective factors for reversing Pb neurotoxicity.

Objective: We evaluated the modifying influence of a delta-aminolevulinic acid dehydratase (ALAD) polymorphism on the relation between lead burden and cognition among older men., Methods: Information on ALAD genotype, lead measurements, potential confounders, and cognitive testing was collected from 982 participants. For each cognitive test and lead biomarker, we fit separate multiple linear regression models, which included an interaction term for ALAD genotype and the lead biomarker and adjusted for potential confounders., Results: With higher levels of tibia lead, ALAD 1-2/2-2 carriers exhibited worse performance on a spatial copying test in comparison with ALAD 1-1 carriers (P interaction = 0.03). However, there was no consistent pattern of an ALAD genotype-lead interaction for the other tests., Conclusions: The results provide some evidence that ALAD genotype may modify the relation between lead and cognition among older men with low lead burden. However, future work in this area is needed to confirm these suggestive findings.

The rate of acquisition of drug self-administration and the return to drug seeking are important elements of the overall drug profile, and are essential factors in understanding risks associated with drug abuse. Experiment 1 examined the effects of perinatal (gestation/lactation) lead exposure on adult rates of acquisition of intravenous (i.v.) methamphetamine self-administration. Experiment 2 investigated the effects of perinatal lead exposure on drug-maintained responding in a reinstatement (relapse) paradigm. In Experiment 1, female rats were gavaged daily with 0 or 16 mg lead for 30 days prior to breeding with nonexposed males. Lead exposure continued through gestation and lactation and was discontinued at weaning (postnatal day [PND] 21). Male rats born to control or lead-exposed dams were tested daily as adults in an acquisition paradigm that incorporated both Pavlovian and operant components. An initial 3-h autoshaping period preceded a 3-h self-administration period. For 35 daily training sessions i.v. methamphetamine infusions [inf] (0.02 mg/kg) were paired with the extension and retraction of a lever (autoshaping), while inf occurred during self-administration only when a lever press was executed (FR-1). In Experiment 2 animals developmentally exposed to lead were trained on an FR-2 to self-administer methamphetamine (0.04 mg/kg/inf) and then placed on an extinction schedule prior to receiving intraperitoneal (i.p.) priming injections of saline, 0.50, 1.00, or 1.50 mg/kg methamphetamine. The findings from Experiment 1 showed that acquisition was delayed in rats born to lead-exposed dams gavaged daily with 16 mg lead throughout gestation and lactation when a 0.02-mg/kg/inf of methamphetamine served as the reinforcement outcome. Additional data from Experiment 2 indicated priming cues (injections of methamphetamine [i.p.]) administered after extinction were less likely to occasion a return to drug seeking (relapse) in the 16-mg group relative to the 0-mg control group. These results suggest perinatal lead exposure alters patterns of methamphetamine self-administration during the adult cycle.

The transition to synthetic chemicals as a popular method of insect control in the United States was one of the most critical developments in the history of American agriculture. Historians of agriculture have effectively identified the rise and charted the dominance of early chemical insecticides as they came to define commercial agriculture between the emergence of Paris green in the 1870s and the popularity of DDT in the 1940s and beyond. Less understood, however, are the underlying mechanics of this transition. this article thus takes up the basic question of how farmers and entomologists who were once dedicated to an impressively wide range of insect control options ultimately settled on the promise of a chemically driven approach to managing destructive insects. Central to this investigation is an emphasis on the bureaucratic maneuverings of Leland O. Howard, who headed the Bureau of Entomology from 1894 to 1927. Like most entomologists of his era, Howard was theoretically interested in pursuing a wide variety of control methods--biological, chemical, and cultural included. In the end, however, he employed several tactics to streamline the government's efforts to almost exclusively support arsenic and lead-based chemical insecticides as the most commercially viable form of insect control. While Howard in no way "caused" the national turn to chemicals, this article charts the pivotal role he played in fostering that outcome.

Many environmental risk factors for antisocial and violent behavior have been described. In recent years, this topic has become widely researched in the fields of environmental health, psychology, sociology, and many other disciplines. The results from a myriad of studies have shown that the etiologies of violent and aggressive behavior range from definitive biological environmental stressors like lead or polychlorinated biphenyls to various socio-cultural environmental stressors, such as social, economic, and racial factors. The aim of this paper is (a) to provide an overview of the specific effects of the environmental stressors that have been associated with violent behavior, and (b) to discuss current policies and regulations implemented by the United States government for minimizing exposure to environmental toxins contributing to violence in our society.

The goals were to determine if lead exposure is associated with cerebral white matter changes (WMC) and if so, does WMC mediate the relation between lead and psychomotor slowing as measured by Grooved Pegboard (GP). In the literature, age is the strongest predictor of WMC and therefore 61 lead smelter workers age 50 and under were included in the study population. Mean (range) age was 40 (23-50) years, years of education was 9 (0-13), duration of employment was 19 (1-26), current blood lead (PbB) was 29 (16-42) microg/dl, working lifetime weighted integrated blood lead (IBL) was 826 (65-1451) microg year/dl, working lifetime weighted average blood lead (TWA) was 42 (17-59) microg/dl, and bone lead (PbBn) was 39 (-12-90) microg Pb/g bone mineral. WMC, recorded as hyperintensities on T2-weighted MRI of the brain were graded. Lead variables were entered in a logistic regression attempting to differentiate normal versus abnormal MRI, after controlling for age and cerebrovascular risk factors. Direct effects of lead on GP and indirect effects of lead on GP through WMC was modeled using multiple linear regression analyses after controlling for the covariates. WMC were present in 23% of MRIs. Logistic regression of WMC on lead exposure metrics demonstrated significantly elevated odds ratios for IBL, TWA, and PbBn after the covariates. Of the lead exposure variables, IBL (beta=0.339, p<0.10) had a larger direct effect on GP after adjusting for the covariates than PbBn (beta=0.265, p<0.10). After adjusting for the lead term and covariates WMC accounted for an additional effect on GP performance after PbBn (beta=0.261, p<0.10) and after IBL (beta=0.278, p<0.05). Path analysis demonstrated that some of the relationship of both PbBn and IBL with GP is mediated by WMC.

The study of neurological impacts of toxicants has emphasized neuropsychological tests as important outcome variables. Direct assessment of neural substrates of environmental impacts could offer many advantages. I discuss our use of magnetic resonance spectroscopy (MRS) in the neurological assessment of adult lead poisoning of monozygotic twins as an example. Cognitive testing showed frontal lobe dysfunction in both twins, and more dramatic hippocampal dysfunction in the twin with higher lead exposure (JG). MRS showed lower N-acetylaspartate/creatine ratios in JG. The findings illustrate the potential utility of MRS in assessing impacts of not only lead, but other toxicants as well.

Objective: To determine whether cumulative lead dose in former organolead workers was associated with MRI measures of white matter lesions (WML) and global and structure-specific brain volumes., Methods: MRIs, tibia lead, and other measures were obtained from 532 former organolead workers with a mean age of 56 years and a mean of 18 years since last occupational exposure to lead. Cumulative lead dose was measured by tibia lead, obtained by X-ray fluorescence, and expressed as microg lead per gram of bone mineral (microg Pb/g). WML were evaluated using the Cardiovascular Health Study grading scale. A total of 21 global and specific brain regions were evaluated., Results: A total of 36% of individuals had WML grade of 1 to 7 (0 to 9 scale). Increasing peak tibia lead was associated with increasing WML grade (p = 0.004). The adjusted OR for a 1 microg Pb/g increase in tibia lead was 1.042 (95% CI = 1.021, 1.063) for a CHS grade of 5+ (> or = 5 vs < 5). In linear regression, the coefficient for tibia lead was negative for associations with all structures. Higher tibia lead was significantly related to smaller total brain volume, frontal and total gray matter volume, and parietal white matter volume. Of nine smaller specific regions of interest, higher tibia lead was associated with smaller volumes for the cingulate gyrus and insula., Conclusions: These data suggest that cumulative lead dose is associated with persistent brain lesions, and may explain previous findings of a progressive decline in cognitive function.

Benjamin Franklin (1706-1790), who is better known in other fields, especially colonial politics and international diplomacy, was an early, major contributor to the neurosciences from the New World. Among his accomplishments are: experiments on medical electricity as a possible cure for the palsies and hysteria; the first descriptions of how electricity affecting the brain can cause a specific type of amnesia; supporting the idea that cranial shocks might provide a cure for melancholia; showing that the cures performed by the Mesmerists to remove obstructions, including nerve blockages, rest on gullibility and suggestion, and recognizing the dangers, including those to the nerves, posed by exposure to lead. Franklin?s neuroscience was firmly based on experiments, careful observations, and hard data ? and finding clinical relevance for new discoveries was always on his mind.

Lead paint is one source of exposure for lead poisoning; however, recent Latino and other immigrant populations are also at risk of exposure through ceramic cooking pots with lead glaze, some imported candies, and certain stomach ailment home remedies. Public health agencies and practitioners acknowledge that Latino families should be educated about lead poisoning prevention but report barriers to conducting outreach and education in Latino communities. This study reports findings from focus groups and interviews with the local Latino immigrant community and professionals on (1) current knowledge and beliefs about lead poisoning and (2) recommendations of culturally appropriate educational strategies.

The effects of developmental lead exposure on the emotional reactivity, contextual fear conditioning and neurogenesis in the dentate gyrus of 60-80 days-old rats were studied. Wistar rat pups were exposed to 0.2% lead acetate via their dams' drinking water from postnatal day (PND) 1 to PND 21 and directly via drinking water from weaning until PND 30. At PND 60 and 80 the level of anxiety and contextual fear conditioning were studied, respectively. At PND 80 all animals received injections of BrdU to determine the effects of Pb on the generation of new cells in the dentate gyrus of hippocampus and on their survival and differentiation patterns. The results of the present study demonstrate that developmental lead exposure induces persistent increase in the level of anxiety and inhibition of contextual fear conditioning. Developmental lead exposure reduced generation of new cells in the dentate gyrus and altered the pattern of differentiation of BrdU-positive cells into mature neurons. A lower proportion of BrdU-positive cells co-expressed with the marker for mature neurons, calbindin. In contrast, the proportions of young not fully differentiated neurons and proportions of astroglial cells, generated from newly born cells, were increased in lead-exposed animals. Our results demonstrate that developmental lead exposure induces persistent inhibition of neurogenesis and alters the pattern of differentiation of newly born cells in the dentate gyrus of rat hippocampus, which could, at least partly, contribute to behavioral and cognitive impairments observed in adulthood.

Elevated lead (Pb) burden and high stress levels are co-occurring risk factors in low socioeconomic status (SES) children. Our previous work demonstrated that maternal Pb exposure can permanently alter hypothalamic-pituitary-adrenal (HPA) axis function and responsivity to stress challenges in offspring. The current study sought to determine the consequences of chronic Pb exposures initiated later in development combined with variable intermittent stress challenges. Male rats were exposed chronically from weaning to 0, 50, or 150 ppm Pb acetate drinking solutions (producing blood Pb levels of <5, 9-15, and 23-27 mug/dl, respectively). Pb itself decreased basal plasma corticosterone, with greater effects at 50 than 150 ppm; 150 ppm reduced both cytosolic and nuclear glucocorticoid receptor binding. Responsivity to stress challenges including novelty, cold, and restraint, was measured as changes in Fixed Interval (FI) schedule-controlled behavior in a subset of rats within each group. FI performance was modified by novelty stress only in Pb-treated rats, whereas cold and restraint stress effects were comparable across groups. Novelty elevated corticosterone equivalently across groups, but cold stress markedly increased corticosterone only in Pb-treated groups. The pattern of Pb-induced changes in serotonin (5-HT) or its metabolite 5-HIAA in frontal cortex, nucleus accumbens, striatum, and hypothalamus resembled that observed for basal corticosterone levels indicating a relationship between these variables. In addition to suggesting the potential for HPA axis-mediated effects of Pb on the central nervous system, these findings also raise questions about whether single chemicals studied in isolation from other relevant risk factors can adequately identify neurotoxic hazards.

Acoustic analysis of infants crying, a sensitive and selective index for measuring the effect of pre and perinatal lead exposure, may provide an early marker for central nervous system damage produced by the toxic. The present study evaluated the effects of exposure to low lead levels during perinatal and early postnatal periods on ultrasonic vocalization (USV), an early behavior of rat pups essential to their development. Non-sexually experienced females were gavaged daily with 8, 16 or 24 mg/kg of lead acetate or the control solution (1 ml/kg) for 30 days prior to breeding and until their pups were weaned. After crossover of dams, pups had been exposed to lead during pregnancy+lactation, pregnancy or lactation. The physiological variables measured on postnatal days 7 or 14 were USV, locomotion, rectal temperature, body weight and blood lead levels. Lead exposition during pregnancy+lactation, pregnancy or lactation induced a significant dose-dependent decrease of USV of 7-day-old pups. On the contrary, lead exposition during the different phases of pregnancy induced a significant dose-dependent increase of USV in 14-day-old rat pups. Blood lead levels varied from 5.7 to 36.5 microg/dl in pups. Body weight and temperature were not influenced by lead exposition. Lead-exposed 14-day-old pups were significantly more active. This study provides evidence of developmental changes in USV emission in rat pups exposed with low lead levels.

Lead poisoning remains an occupational hazard in Taiwan. Many studies, based on crossed-section design, have focused on changes in lead-associated neurobehavioral dysfunctions that occur at increased blood lead levels. This study evaluates the changes in neurobehavioral performance of lead workers as blood levels are reduced. We tested 27 lead workers in a lead glaze factory using the computer-based and automated Chinese edition of Neurobehavioral Evaluation System 2 (C-NES II) in 1994, 1996, and 1997. The association of blood lead levels and C-NES II results were analyzed by longitudinal data analysis methods, repeated ANOVA and mixed model analyses after adjustment for potential confounders. Over these 4 years, the mean lead blood levels of workers were reduced from 26.3(SD=12.0) to 8.3(SD=6.9) microg/dL. Based on a mixed model analysis, we found that the negative effects of exposure to lead on neurobehavioral performance can be reversed to some extent with lowering levels of blood lead. During this period, we found significant improvements in 3 subtests: finger tapping, pattern comparison reaction time, and memory. This study tentatively concluded that reversibility of the neurobehavioral performance after reduction of the lead exposure, which encourages industrial hygiene and personal health promotion to reduce their body lead burden. However, though use of NES is more sensitive to detect the changes, the chronic symptoms (using standardized questionnaire) were found to decline slowly when blood lead level is reduced, with no statistically significant difference. The result means that to avoid the lead exposure primarily is essential to prevent chronic symptoms. We conclude that the most important way to prevent and possibly reverse chronic symptoms of lead poisoning remains to be the avoidance of exposure to lead.

Anecdotal observations suggest that neurological impairments associated with petrol (gasoline) sniffing resolve with abstinence, although these effects have not been proven empirically. Severe exposure to leaded petrol may induce a lead encephalopathy that extends beyond any acute intoxication and requires emergency hospital treatment. Previously, in chronic petrol sniffers, we showed neurological, saccadic, and cognitive abnormalities that were more severe in petrol sniffers with a history of hospitalization for lead encephalopathy, and that correlated with blood lead levels and the length of time of sniffing petrol. Ex-petrol sniffers showed a qualitatively similar but quantitatively less severe pattern of impairment. Petrol sniffing was stopped completely in one of the study communities by modifying social, occupational, and recreational opportunities. After 2 years, we obtained biochemical and neurobehavioral (neurological, saccade, and cognitive) data from all available participants of the earlier study including 10 nonsniffers and 29 chronic petrol sniffers, with six of these individuals previously receiving hospital treatment for lead encephalopathy. Here, we report that blood lead was reduced and that neurobehavioral impairments improved, and in many cases normalized completely. The most severe petrol-related neurobehavioral impairment was observed among individuals who had longer histories of abuse and higher blood lead levels, and among petrol sniffers with a history of lead encephalopathy. Those with the greatest extent of neurobehavioral impairment showed the greatest degree of improvement with abstinence, but were less likely to recover completely. This is the first direct evidence that neurological and cognitive impairment from chronic petrol sniffing ameliorates with abstinence and may recover completely.

Objective: Some children in the United States continue to be exposed to levels of lead that increase their risk for lowered intellectual functioning and behavior problems. It is unclear whether chelation therapy can prevent or reverse the neurodevelopmental sequelae of lead toxicity. The objective of this study was to determine whether chelation therapy with succimer (dimercaptosuccinic acid) in children with referral blood lead levels between 20 and 44 microg/dL (0.96-2.12 micromol/L) at 12 to 33 months of age has neurodevelopmental benefits at age 7 years., Methods: The Treatment of Lead-Exposed Children (TLC) study is a randomized, double-blind, placebo-controlled trial that was conducted between September 1994 and June 2003 in Philadelphia, PA; Newark, NJ; Cincinnati, OH; and Baltimore, MD. Of 1854 referred children who were between the ages of 12 to 33 months and screened for eligibility, 780 were randomized to the active drug and placebo groups stratified by clinical center, body surface area, blood lead level, and language spoken at home. At 7 years of age, 647 subjects remained in the study. Participants were randomly assigned to receive oral succimer or placebo. Up to 3 26-day courses of succimer or placebo therapy were administered depending on response to treatment in those who were given active drug. Eighty-nine percent had finished treatment by 6 months, with all children finishing by 13 months after randomization. All participants received residential lead hazard control measures before treatment. TLC subjects also received a daily multivitamin supplement before and after treatment(s) with succimer or placebo. Scores on standardized neuropsychological measures that tap cognition, behavior, learning and memory, attention, and neuromotor skills were measured., Results: Chelation therapy with succimer lowered average blood lead levels for approximately 6 months but resulted in no benefit in cognitive, behavioral, and neuromotor endpoints., Conclusion: These new follow-up data confirm our previous finding that the TLC regimen of chelation therapy is not associated with neurodevelopmental benefits in children with blood lead levels between 20 and 44 microg/dL (0.96-2.17 micromol/L). These results emphasize the importance of taking environmental measures to prevent exposure to lead. Chelation therapy with succimer cannot be recommended for children with blood lead levels between 20 and 44 microg/dL (0.96-2.12 micromol/L).

Seventy-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.

Although there is empirical support for the link between executive functioning (EF) and visual memory among adults, there has been less exploration of this link among children, especially adolescents. We examined the relation between several EF measures and performance on the Rey-Osterrieth Complex Figure (RCF) in a sample of 160 community adolescents. Each was administered the Wisconsin Card Sorting Test (WCST), Conners Continuous Performance Test (CPT), and the RCF, scored using Bernstein and Waber's (1996) Developmental Scoring System (DSS). Ability to organize the RCF related to memory encoding/retrieval, but not to long-term storage. Indexes derived from the WCST and CPT failed to correlate with any RCF index, raising questions about the relation between DSS scores and EF. Even so, data supported the convergent validity of the DSS system as a reflection of visual-constructional ability and provided evidence of the importance of organizational strategies to visual memory among adolescents.

Background: Lead is neurotoxic; yet, whether cognitive decline in older persons is associated with lead exposure is unknown. We studied whether lead exposure biomarkers are associated with cognitive test scores, as well as the modifying effects of age on the lead-cognition relationship., Methods: Lead exposure biomarkers and Mini-Mental Status Exam (MMSE) scores were measured among subjects in the Normative Aging Study. Multiple linear and logistic regression analyses were performed to examine the cross-sectional association of these 2 variables., Results: We found an odds ratio (OR) of 2.1 for MMSE <24 with an increase from the lowest to the highest quartile of patella lead levels (95% confidence interval [CI] = 1.1 to 4.1). From the lowest to the highest quartile of blood lead the OR for low MMSE was 3.4 (CI = 1.6 to 6.2). There was an interaction between lead biomarkers and age. Among subjects in the lowest quartile of patella lead levels, MMSE score decreased by 0.03 points per year (CI = -0.07 to 0.005), whereas in the highest quartile, MMSE score decreased by 0.13 points per year (CI = -0.19 to -0.07). Similar interactions were found between blood lead levels and age., Conclusions: Increased levels of lead in bone and blood are inversely associated with cognitive performance among older men. Lead exposure might accelerate age-associated cognitive decline.

Numerous observations in clinical and preclinical studies indicate that the developing brain is particular sensitive to lead (Pb)'s pernicious effects. However, the effect of gestation-only Pb exposure on cognitive functions at maturation has not been studied. We investigated the potential effects of three levels of Pb exposure (low, middle, and high Pb: 0.03%, 0.09%, and 0.27% of lead acetate-containing diets) at the gestational period on the spatial memory of young adult offspring by Morris water maze spatial learning and fixed location/visible platform tasks. Our results revealed that three levels of Pb exposure significantly impaired memory retrieval in male offspring, but only female offspring at low levels of Pb exposure showed impairment of memory retrieval. These impairments were not due to the gross disturbances in motor performance and in vision because these animals performed the fixed location/visible platform task as well as controls, indicating that the specific aspects of spatial learning/memory were impaired. These results suggest that exposure to Pb during the gestational period is sufficient to cause long-term learning/memory deficits in young adult offspring.

This Special Section on the Neurobehavioral Effects of Environmental Lead includes empirical reports from three major longitudinal prospective studies and a review of animal research modeling effects of lead on human cognition. This Introductory article addresses a fundamental controversy in lead and other epidemiologic research. It is argued that, contrary to conventional wisdom, valid causal inferences can be made from correlational research. Justification for this is to be found in contemporary frameworks drawn from the field of the philosophy of science; an essential, but often neglected perspective for such metatheoretical issues as causal inference. It is concluded that the nonexperimental methods described in the articles comprising this Special Section can, indeed, contribute to causal formulations of lead effects on human development, and that such inferences are not exclusive to experimental evidence.

Experimental studies, relying primarily on rodent and non-human primate models, have produced compelling evidence supporting effects of chronic low level lead exposure on learning, with the magnitude of those effects possibly modulated by developmental period of exposure and learning paradigm parameters. In contrast, changes in memory are not systematically demonstrated. The impact of lead exposure on attention has yet to be clearly delineated in either human or experimental studies, although impulsivity or aversion to delay appears to be a sensitive component of attention that may be targeted.