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 Table of Contents  
GUEST EDITORIAL
Year : 2017  |  Volume : 1  |  Issue : 2  |  Page : 62-64

Lead and its association with mental illness


Department of Psychiatry, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Date of Web Publication8-Dec-2017

Correspondence Address:
Sandeep Grover
Department of Psychiatry, Postgraduate Institute of Medical Education and Research, Chandigarh - 160 012
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/aip.aip_44_17

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How to cite this article:
Grover S, Jhanda S. Lead and its association with mental illness. Ann Indian Psychiatry 2017;1:62-4

How to cite this URL:
Grover S, Jhanda S. Lead and its association with mental illness. Ann Indian Psychiatry [serial online] 2017 [cited 2018 Feb 24];1:62-4. Available from: http://www.anip.co.in/text.asp?2017/1/2/62/220258




  Introduction Top


Lead is one of the oldest established poisons, found naturally in the earth's crust, and has been used by humankind for many purposes since ancient times.[1] Lead has also been identified as one of the ten chemicals that are of major health concern to the public. Lead is used widely, and the various sources of environmental contamination by lead include activities such as manufacturing and recycling activities, mining, and smelting. In few countries, leaded gasoline and leaded paint still continue to be additional sources of lead exposure. Other sources of exposure to lead include lead crystal glassware, lead pipes, stained glass, ammunition, jewelry, toys, and some traditional medicines.

Exposure to lead can have harmful effects on participants of any age group. However, young children absorb four to five times the ingested lead as compared to adults and are thus more vulnerable to its adverse effects. Furthermore, children's age-related mouthing behavior results in intake of nonedible substances contaminated by lead, for example, contaminated soil and flakes of lead-containing paint. The risk is further increased in children with pica. Children suffering from malnutrition are also more vulnerable to lead because there is more absorption of lead if there is deficiency of calcium. Hence, body starts handling lead similar to calcium.[2],[3],[4] There is also evidence of mass lead poisoning deaths in children in Nigeria and Senegal.[5] Here, main sources of exposure of lead were soil and dust contamination mainly from mining and battery recycling. Based on the 2015 data, the Institute for Health Metrics and Evaluation [6] at University of Washington reported that exposure to lead was responsible for 4,94,550 deaths and loss of 9.3 million disability-adjusted life years. It is also reported that lead exposure was responsible for a certain percentage of global burden of health conditions such as idiopathic intellectual disability(12.4%), stroke(2.4%), and ischemic heart disease(2.5%).

Considering the link of lead exposure and development of mental disorders, it is important to estimate the impact of lead on mental morbidity in any country. Unfortunately, there is lack of exact data from India, in terms of exposure to lead among children and participants of various age groups. Keeping this in mind the effort of Anusa and Rooban,[7] who estimated the impact of lead exposure on mental morbidity among children and adolescents based on global burden of diseases data is an important contribution to the literature and provides important insights into the problems and makes everyone aware of this problem.


  Effects of Lead on the Body Top


Lead can lead to toxic effects is known since 3 millennia and knowledge about its toxic effects among children are known for more than 100years. After lead enters the body (ingestion being the most common route), although it is redistributed to various organs such as bones, liver, brain, and kidneys, it mainly accumulates in bones and teeth. During pregnancy, the lead stores from bones and teeth are mobilized into the blood, thereby exposing the fetus.[1]

Mechanism of lead-induced neurotoxic effects

Among the various organs of the body, the major toxic effects of lead have been noted on the brain. The effects of lead on the brain cannot be explained by only single mechanism. Lead is considered to have direct neurotoxic effect on brain and has been shown to be associated with apoptosis, excitotoxicity of the brain, storage and release of various neurotransmitters, mitochondria, second messenger system, cerebrovascular endothelial cells, and both the astroglial and oligodendritic cells. Lead is known to be able to substitute calcium and this ability has been implicated in many of its toxic effects.[1] The ability of lead to substitute calcium has been shown to initiate mitochondrial dysfunction, which disrupts the energy levels in the cell, which ultimately starts the apoptosis cascade and lead to neuronal death. Lead has also been shown to alter the calcium-dependent release of acetylcholine, dopamine and amino acid neurotransmitters.[1] Lead has been demonstrated to have toxic effects on oligodendroglia and astroglia by delaying the differentiation of glial progenitors and also leads to hypomyelination and demyelination.[1] Indirect neuronal damage by lead has been shown to bemediated by its ability to disrupt heme synthesis, which leads to increase in the precursor δ-aminolevulinic acid(ALA). ALA is known to inhibit the release of gamma-aminobutyric acid(GABA)-mediated neurotransmission and also compete with GABA at receptors. Accordingly, lead has been shown to cause anemia, which also contributes to neurocognitive deficits.[1] Further lead also disrupts the thyroid axis, which further contributes to psychiatric manifestations and cognitive deficits.[1] Symptoms due to exposure to lead can appear immediately after exposure or may be delayed. Common symptoms of lead intoxication include such as intellectual decline, behavioral problems, and vision loss. Recently, violence, antisocial behavior, and delinquency have also been associated with high exposures of lead.[8]

Impact of high levels of lead on development

High levels of lead exposure can cause symptomatic poisoning among children. The various manifestations of exposure to high dose of lead include fatigue, colic, constipation, anemia and features suggestive of central nervous system involvement, which can range widely from poor concentration to stupor. In severe cases, this can also lead to delirium, convulsions, and coma.[2] The neurological and behavioral consequences of lead are understood to be irreversible. These factors thus lead to an altered neurodevelopment in children wherein most vulnerable period is during prenatal life and extending through infancy and early childhood. Children who are able to survive acute high-dose lead poisoning can have lasting sequelae in the form of brain damage, intellectual disability, and behavioral problems.[8],[9]

Studies have shown that high levels of lead(>10 μg/dl) can also lead to adverse effects among developing children. Astudy evaluated the association of lead exposure in early childhood and neuropsychological testing at 7years of age. The study included 494 children who belonged to lead-smelting community in Australia. Assessment of lead levels was done in antenatal period, i.e., by maternal blood samples, at birth through umbilical cord blood, and then at 6months, 15months, and 2years of age followed by yearly blood levels till 7years of age. During follow-up, it was noted that, by 2 and 4years of age, exposure to high blood lead levels was associated with deficits in intellectual functioning. It was seen that for every increase in blood levels of lead from 10 to 30 mg/dl, there was reduction of 4.4–5.3 intelligence quotient(IQ) points after controlling for multiple confounding variables. This represented 4%–5% deficit in IQ scores.[10]

Low levels of lead and impact on development

In 1991, Centre for Disease Control and Prevention declared lead blood level of 10 μg/dl to initiate public health action. At the same time, it was also emphasized that though 10 μg/dl was useful in risk management, by no means this level should serve as a measure of lead toxicity. It is important to know that there has been no threshold value identified for lead toxicity yet.[1]

A study evaluated the association of blood lead levels with IQ scores among 1331 children who were part of the seven international population-based longitudinal cohort studies. These children were followed from birth/infancy up to 5–10years of age to understand the impact of maximal measured blood lead levels of<10 μg/dL on intelligence. After controlling for the covariates, using a log-linear model, the authors noted a decline in IQ by 6.9 points with increase in blood lead levels from 2.4 to 30 μg/dl. However, the interesting observation was decline in IQ points was highest among those with blood lead from 2.4 to 10 μg/dl, i.e., 3.9 points. Those with blood lead from 10 to 20 μg/dl, and 20–30 μg/dl had reduction in 1.9 and 1.1 IQ points, respectively. Children who had maximum blood lead levels<7.5 mg/dl had significantly more intellectual decline compared to those whose maximal blood lead concentration was more than 7.5 mg/dl(P=0.015).[11] A link between low level exposure to lead during early development and occurrence of neurobehavioral deficits in later childhood and adolescence has also been shown.[12],[13] Accordingly, it can be said that, at present, it is not clear what should be the optimal lead levels.

Association of lead and mental illnesses among children and adults

In children, lead exposure can lead to various adverse effects such as causing brain damage, intellectual disability, behavioral problems, hyperactivity, hearing loss, and deterioration in school performance.[9],[14],[15],[16] A meta-analysis evaluated the relationship between blood lead levels and IQ in school-going children. Asignificant association was observed between blood levels of lead and child's IQ. Increase in blood lead levels from 10 to 20 μg/dl was associated with decline of 2.6 IQ points. This study also concluded that there was no threshold of lead blood levels that could be determined to have an impact on the IQ.[17] A case study evaluated the impact of exposure to lead among two boys(cousins, 9 and 10years old), living in the same house, but one of them had exposure to lead and the other did not. It was observed that the boy who was exposed to lead had significant difficulties in areas of reading, writing, and mathematics, whereas no such abnormalities were observed in the other boy, who had no lead exposure. On neuroimaging, magnetic resonance imaging in both the boys did not reveal any abnormality, whereas magnetic resonance spectroscopy revealed significant impairments in brain metabolites in the boy exposed to lead.[18] Exposure to high lead levels has also been shown to be associated with problems in the areas of memory, executive functions, attention, processing speed, language, visuospatial and motor skills, and affect/mood are explored.[19] Among the childhood-onset disorder, evidence also suggests an association of both low and high lead exposure with attention-deficit hyperkinetic disorder.[20],[21]

Studies have also shown association of high exposure to lead(blood lead levels>15 mg/dl) with higher externalizing and internalizing scores.[22] Data also suggest that exposure to blood lead levels in the range of 10–24.9 mg/dl contributes to lower mean Mental Developmental Index(determined by Bayley Scale of Infant Development, second edition) score by 6.3 points, when compared with children whose blood lead levels were in the range of 0–9.9 mg/dl.[23] Other mental problems noted in children exposed to lead include criminal behavior and juvenile delinquency.[24]

Exposure to high lead levels among young adults have also been reported to be associated with increased risk of development of major depression [25],[26] and panic disorder [25] and generalized anxiety disorder.[26] Exposure to high lead levels in the prenatal period has been linked with schizophrenia and antisocial behavior.[26]

Factors to be considered while evaluating the effect of lead on neurodevelopment

It has been emphasized that the role of child's caregivers and environment need to be considered while evaluating the effects of lead on child's development. This is because the personal, family, and psychosocial factors account more for neurodevelopmental measures than blood lead levels. As per National Research Council, Washington,[27] a critical time window up to 2years of age is considered for lead to impact development. Both high and low lead levels have been shown to have adverse effects on the developing brain, which are stated below.


  Conclusion Top


Lead is a toxic metal that affects almost every system in the body and central nervous system being its main target. Various tissues in the body can be used to ascertain lead levels such as blood, bone, hair, tooth, nail, urine, and umbilical cord blood; however, blood is commonly used as a biomarker across studies. Children are particularly vulnerable to develop adverse effects with lead than adults. Both high and low levels of lead in children are associated with brain damage, intellectual disability, hyperactivity, behavioral problems, antisocial behavior, violence, and juvenile delinquency. There is no threshold for lead levels to have its adverse effects. Furthermore, effects of lead exposure in childhood persist into adulthood. Hence, this is an area of major public health concern. Accordingly, there is an urgent need to evaluate this in the Indian context by properly designed studies. There is an urgent need to increase awareness of general public about the same.



 
  References Top

1.
LidskyTI, SchneiderJS. Adverse effects of childhood lead poisoning: The clinical neuropsychological perspective. Environ Res 2006;100:284-93.  Back to cited text no. 1
    
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Institute for Health Metrics and Evaluation(IHME). GBD Compare. Seattle, WA: IHME, University of Washington; 2017.  Back to cited text no. 6
    
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AnusaM, RoobanT. Burden of exposure to lead as a risk factor for mental illness in Indian children 1990–2015: Asystematic analysis based on global burden of disease. Ann Indian Psychiatry 2017;1:88-96.  Back to cited text no. 7
  [Full text]  
8.
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RoganWJ, WareJH. Exposure to lead in children–How low is low enough? N Engl J Med 2003;348:1515–16.  Back to cited text no. 9
    
10.
BaghurstPA, McMichaelAJ, WiggNR, VimpaniGV, RobertsonEF, RobertsRJ, etal. Environmental exposure to lead and children's intelligence at the age of seven years. The Port Pirie Cohort Study. NEngl J Med 1992;327:1279-84.  Back to cited text no. 10
    
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LanphearBP, HornungR, KhouryJ, YoltonK, BaghurstP, BellingerDC, etal. Low-level environmental lead exposure and children's intellectual function: An international pooled analysis. Environ Health Perspect 2005;113:894-9.  Back to cited text no. 11
    
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RosenJF. Health effects of lead at low exposure levels. Expert consensus and rationale for lowering the definition of childhood lead poisoning. Am J Dis Child 1992;146:1278-81.  Back to cited text no. 12
    
13.
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CarpenterDO. Effects of metals on the nervous system of humans and animals. Int J Occup Med Environ Health 2001;14:209-18.  Back to cited text no. 14
    
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CanfieldRL, Henderson CR Jr. Cory-SlechtaDA, CoxC, JuskoTA, LanphearBP, etal. Intellectual impairment in children with blood lead concentrations below 10 microg per deciliter. NEngl J Med 2003;348:1517-26.  Back to cited text no. 16
    
17.
SchwartzJ. Low-level lead exposure and children's IQ: Ameta-analysis and search for a threshold. Environ Res 1994;65:42-55.  Back to cited text no. 17
    
18.
TropeI, Lopez-VillegasD, LenkinskiRE. Magnetic resonance imaging and spectroscopy of regional brain structure in a 10-year-old boy with elevated blood lead levels. Pediatrics 1998;101:E7.  Back to cited text no. 18
    
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MasonLH, HarpJP, HanDY. Pb neurotoxicity: Neuropsychological effects of lead toxicity. Biomed Res Int 2014;2014:840547.  Back to cited text no. 19
    
20.
ParkJH, SeoJH, HongYS, KimYM, KangJW, YooJH, etal. Blood lead concentrations and attention deficit hyperactivity disorder in Korean children: Ahospital-based case control study. BMC Pediatr 2016;16:156.  Back to cited text no. 20
    
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DaneshparvarM, MostafaviSA, Zare JeddiM, YunesianM, MesdaghiniaA, MahviAH, etal. The role of lead exposure on attention-deficit/hyperactivity disorder in children: ASystematic review. Iran J Psychiatry 2016;11:1-4.  Back to cited text no. 21
    
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MendelsohnAL, DreyerBP, FiermanAH, RosenCM, LeganoLA, KrugerHA, etal. Low-level lead exposure and behavior in early childhood. Pediatrics 1998;101:E10.  Back to cited text no. 23
    
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NeedlemanHL, GatsonisCA. Low-level lead exposure and the IQ of children. Ameta-analysis of modern studies. JAMA 1990;263:673-8.  Back to cited text no. 24
    
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BouchardMF, BellingerDC, WeuveJ, Matthews-BellingerJ, GilmanSE, WrightRO, etal. Blood lead levels and major depressive disorder, panic disorder, and generalized anxiety disorder in US young adults. Arch Gen Psychiatry 2009;66:1313-9.  Back to cited text no. 25
    
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