Environmental Lead Exposure and ADHD Symptom Domains
Background Low-level environmental exposure to lead has been associated with both reduced intelligence and symptoms of attention deficit/hyperactivity disorder (ADHD). However, few studies have estimated the association of lead and intelligence independent of ADHD, and it is not clear from previous studies whether lead is associated with both inattention and impulsivity ADHD symptoms.
Objectives We estimated mutually adjusted associations of environmental lead exposure with both intelligence and ADHD symptoms, and associations between lead and specific ADHD-related domains.
Methods Blood lead concentrations were measured in a general population of 1,001 children 8–11 years of age. We used multivariable linear regression models to estimate associations of blood lead concentrations with IQ scores, teacher and parent ratings of ADHD symptoms, and measures of inattention and impulsivity. Models were adjusted for demographic variables and other environmental exposures (blood levels of mercury and manganese, urinary concentrations of cotinine, phthalate metabolites, and bisphenol A).
Results Associations of blood lead with lower IQ and higher impulsivity were robust to adjustment for a variety of covariates. When adjusted for demographic characteristics, other environmental exposures, and ADHD symptoms or IQ, a 10-fold increase in blood lead concentration was associated with lower Full-Scale IQ (–7.23; 95% CI: –13.39, –1.07) and higher parent- and teacher-rated hyperactivity/impulsivity scores (ADHD Rating Scale, 1.99; 95% CI: 0.17, 3.81 and 3.66; 95% CI: 1.18, 6.13, respectively) and commission errors (Continuous Performance Test, 12.27; 95% CI: –0.08, 24.62). Blood lead was not significantly associated with inattention in adjusted models.
Conclusions Low-level lead exposure was adversely associated with intelligence in school-age children independent of ADHD, and environmental lead exposure was selectively associated with impulsivity among the clinical features of ADHD.
Lead is an environmental neurotoxicant known to interfere with brain development (Canfield et al. 2003; Lanphear et al. 2005; Surkan et al. 2007). Even low-level exposure to lead that is prevalent in daily living has been associated with reduced intelligence, impaired attention, and behavioral problems (Braun et al. 2006, 2008; Chen et al. 2007; Nevin 2007). Environmental lead exposure also has been associated with symptoms of attention deficit/hyperactivity disorder (ADHD) (Braun et al. 2006) and conduct disorder (Braun et al. 2008). However, given that intelligence itself may affect attention and behavior (Chen et al. 2007; Frazier et al. 2004), and that a negative influence of lead on intelligence has been well replicated (Needleman and Gatsonis 1990), at least part of the association between lead and attention and behavior may be mediated by its negative impact on intelligence. Previous studies examining the association between lead burden and neurobehavioral impairments have addressed this issue by adjusting for intelligence level as a covariate (Goodlad et al. 2013).
Thus far, the findings have been inconclusive on whether lead is associated with both the domains of ADHD symptoms (i.e., inattention and hyperactivity/impulsivity), or with only one of the two domains. Profound and pervasive neurological consequences of high-level lead exposure may result in an undifferentiated worsening of ADHD-like symptoms (Needleman 2009), but it has been suggested that low levels of lead exposure may have a greater influence on hyperactivity/impulsivity than on inattention (Nigg et al. 2008, 2010; Stewart et al. 2005, 2006). On the other hand, a recent meta-analysis examined the relation between lead burden and ADHD symptoms, and reported similar associations for the two symptom domains (Goodlad et al. 2013). Studies that aim to resolve this inconsistency require a sufficient sample size and measurements of both behavioral features, as well as neuropsychological indices that can sensitively distinguish between the domains of inattention and hyperactivity/impulsivity.
For example, the Continuous Performance Test (CPT) differentially measures sustained attention and response inhibition (Greenberg and Waldman 1993), and, compared with other neuropsychological tests, has been reported to be the most strongly correlated with a clinical diagnosis of ADHD (Frazier et al. 2004).
Thus, the primary aim of the current study was to differentiate the specific aspects of attentional and behavioral impairments associated with low-level lead exposure by measuring the intelligence level, ADHD-related behaviors (rated by multiple informants), and CPT performance in a large community sample of school-age children.
Secondarily, we aimed to confirm the link between environmental lead exposure and intelligence, independent of ADHD symptoms. If environmental lead exposure is associated with ADHD symptoms, given that ADHD symptoms may interfere with the child's performance in intelligence test (Biederman et al. 2011), it would be reasonable to control for concurrent attention and behavioral problems when estimating the association between lead burden and intelligence, just as we need to control for intelligence level when examining the relation between lead burden and ADHD. Only a few studies investigating the association between lead burden and intelligence have achieved this by measuring both IQ and ADHD-related features in a large group of participants (e.g., Nigg et al. 2008).
Another important issue is potential confounding by other environmental exposures such as mercury, manganese, phthalate metabolites, and bisphenol A (BPA), as well as cotinine (a biomarker for tobacco exposure), each of which may be associated with ADHD (Bouchard et al. 2007; Braun et al. 2009; Cheuk and Wong 2006; Cho et al. 2010b, 2013; Hong et al. 2013; Julvez et al. 2010; Kim BN et al. 2009). Few studies have accounted for multiple environmental risk factors in the same population (Goodlad et al. 2013).
Using data from an initial subsample (n = 667) of the present study's participants (n = 1,089), we previously explored the relationship between lead exposure and ADHD-related problems (Cho et al. 2010b). However, we did not have specific research questions about whether lead burden a) differentially affects intelligence and ADHD, b) predominantly affects impulsivity among the ADHD-related problems, and c) independently affects childhood neurobehavioral outcomes after adjusting for a wide range of potential confounders.
In a large community sample of school-age children, we investigated whether environmental lead exposure is associated with both reduced intelligence and ADHD symptoms, when adjusting for each other as covariates. Next, by adopting an established neuropsychological test of attention, we examined whether lead burden is associated predominantly with a specific domain of ADHD-related problems. Last, we adjusted for blood and urine concentrations of other environmental toxicants to examine potential confounding of associations between lead and cognitive and behavioral outcomes.
Abstract and Introduction
Abstract
Background Low-level environmental exposure to lead has been associated with both reduced intelligence and symptoms of attention deficit/hyperactivity disorder (ADHD). However, few studies have estimated the association of lead and intelligence independent of ADHD, and it is not clear from previous studies whether lead is associated with both inattention and impulsivity ADHD symptoms.
Objectives We estimated mutually adjusted associations of environmental lead exposure with both intelligence and ADHD symptoms, and associations between lead and specific ADHD-related domains.
Methods Blood lead concentrations were measured in a general population of 1,001 children 8–11 years of age. We used multivariable linear regression models to estimate associations of blood lead concentrations with IQ scores, teacher and parent ratings of ADHD symptoms, and measures of inattention and impulsivity. Models were adjusted for demographic variables and other environmental exposures (blood levels of mercury and manganese, urinary concentrations of cotinine, phthalate metabolites, and bisphenol A).
Results Associations of blood lead with lower IQ and higher impulsivity were robust to adjustment for a variety of covariates. When adjusted for demographic characteristics, other environmental exposures, and ADHD symptoms or IQ, a 10-fold increase in blood lead concentration was associated with lower Full-Scale IQ (–7.23; 95% CI: –13.39, –1.07) and higher parent- and teacher-rated hyperactivity/impulsivity scores (ADHD Rating Scale, 1.99; 95% CI: 0.17, 3.81 and 3.66; 95% CI: 1.18, 6.13, respectively) and commission errors (Continuous Performance Test, 12.27; 95% CI: –0.08, 24.62). Blood lead was not significantly associated with inattention in adjusted models.
Conclusions Low-level lead exposure was adversely associated with intelligence in school-age children independent of ADHD, and environmental lead exposure was selectively associated with impulsivity among the clinical features of ADHD.
Introduction
Lead is an environmental neurotoxicant known to interfere with brain development (Canfield et al. 2003; Lanphear et al. 2005; Surkan et al. 2007). Even low-level exposure to lead that is prevalent in daily living has been associated with reduced intelligence, impaired attention, and behavioral problems (Braun et al. 2006, 2008; Chen et al. 2007; Nevin 2007). Environmental lead exposure also has been associated with symptoms of attention deficit/hyperactivity disorder (ADHD) (Braun et al. 2006) and conduct disorder (Braun et al. 2008). However, given that intelligence itself may affect attention and behavior (Chen et al. 2007; Frazier et al. 2004), and that a negative influence of lead on intelligence has been well replicated (Needleman and Gatsonis 1990), at least part of the association between lead and attention and behavior may be mediated by its negative impact on intelligence. Previous studies examining the association between lead burden and neurobehavioral impairments have addressed this issue by adjusting for intelligence level as a covariate (Goodlad et al. 2013).
Thus far, the findings have been inconclusive on whether lead is associated with both the domains of ADHD symptoms (i.e., inattention and hyperactivity/impulsivity), or with only one of the two domains. Profound and pervasive neurological consequences of high-level lead exposure may result in an undifferentiated worsening of ADHD-like symptoms (Needleman 2009), but it has been suggested that low levels of lead exposure may have a greater influence on hyperactivity/impulsivity than on inattention (Nigg et al. 2008, 2010; Stewart et al. 2005, 2006). On the other hand, a recent meta-analysis examined the relation between lead burden and ADHD symptoms, and reported similar associations for the two symptom domains (Goodlad et al. 2013). Studies that aim to resolve this inconsistency require a sufficient sample size and measurements of both behavioral features, as well as neuropsychological indices that can sensitively distinguish between the domains of inattention and hyperactivity/impulsivity.
For example, the Continuous Performance Test (CPT) differentially measures sustained attention and response inhibition (Greenberg and Waldman 1993), and, compared with other neuropsychological tests, has been reported to be the most strongly correlated with a clinical diagnosis of ADHD (Frazier et al. 2004).
Thus, the primary aim of the current study was to differentiate the specific aspects of attentional and behavioral impairments associated with low-level lead exposure by measuring the intelligence level, ADHD-related behaviors (rated by multiple informants), and CPT performance in a large community sample of school-age children.
Secondarily, we aimed to confirm the link between environmental lead exposure and intelligence, independent of ADHD symptoms. If environmental lead exposure is associated with ADHD symptoms, given that ADHD symptoms may interfere with the child's performance in intelligence test (Biederman et al. 2011), it would be reasonable to control for concurrent attention and behavioral problems when estimating the association between lead burden and intelligence, just as we need to control for intelligence level when examining the relation between lead burden and ADHD. Only a few studies investigating the association between lead burden and intelligence have achieved this by measuring both IQ and ADHD-related features in a large group of participants (e.g., Nigg et al. 2008).
Another important issue is potential confounding by other environmental exposures such as mercury, manganese, phthalate metabolites, and bisphenol A (BPA), as well as cotinine (a biomarker for tobacco exposure), each of which may be associated with ADHD (Bouchard et al. 2007; Braun et al. 2009; Cheuk and Wong 2006; Cho et al. 2010b, 2013; Hong et al. 2013; Julvez et al. 2010; Kim BN et al. 2009). Few studies have accounted for multiple environmental risk factors in the same population (Goodlad et al. 2013).
Using data from an initial subsample (n = 667) of the present study's participants (n = 1,089), we previously explored the relationship between lead exposure and ADHD-related problems (Cho et al. 2010b). However, we did not have specific research questions about whether lead burden a) differentially affects intelligence and ADHD, b) predominantly affects impulsivity among the ADHD-related problems, and c) independently affects childhood neurobehavioral outcomes after adjusting for a wide range of potential confounders.
In a large community sample of school-age children, we investigated whether environmental lead exposure is associated with both reduced intelligence and ADHD symptoms, when adjusting for each other as covariates. Next, by adopting an established neuropsychological test of attention, we examined whether lead burden is associated predominantly with a specific domain of ADHD-related problems. Last, we adjusted for blood and urine concentrations of other environmental toxicants to examine potential confounding of associations between lead and cognitive and behavioral outcomes.
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