Brain-wide chemical changes linked to childhood lead exposure.

Apr 18, 2011

Cecil KM, KN Deitrich, M Altaye, JC Egehoff, DM Lindquist, CJ Brubaker and BP Lanphear. 2011. Proton Magnetic Resonance Spectroscopy in adults with childhood lead exposure. Environmental Health Perspectives

Synopsis by Aimin Chen and Wendy Hessler

 2011-0414 lead work area sign



Exposure to moderate levels of lead during childhood can permanently change important brain chemical levels later in life, suggests results from a large brain imaging study. The adults who had higher average blood lead levels as children also had lower levels of several key chemicals that are produced in different brain regions. These brain chemicals are critical to maintaining brain function. This is the first large brain imaging study in young adults followed since birth and adds new insights to the mechanism of lead exposure on brain function.





Lead occurs naturally in rock and soil. The metal has long been used in industrial materials and processses. It was used extensively in gasoline and house paint before the United States banned its use in these products in the 1970s.

However, exposure to lead still occurs mainly through soils, house dust and paint chips – especially in houses built before 1978. Children are most at risk for lead exposure, because they play on the floor and tend to put fingers, toys and other objects in their mouths.

Lead's adverse effects in children include cognitive deficits, aggression, hyperactivity, learning problems, school problems and even delinquent behaviors. No level of lead exposure is considered safe, which means even small exposures can be harmful.

Children are especially susceptible to lead exposure because of their rapidly developing brains. During early life stages, small changes in brain structure and chemical levels can result in long-term deficits in cognition and behavior.

The brain is the most complicated organ in people. It has billions of interconnected nerve cells – the neurons – that coordinate its function. The brain's gray matter – the body of the neurons – and white matter – the projections that relay the signals between neurons – work together for proper function.

It is very difficult to study the brain because the tissue is not accessible. Magnetic Resonance Imaging (MRI) and other brain imaging technologies help researchers understand the effects of lead and other neurotoxic substances on the brain.

Previous brain imaging studies of adults with higher childhood lead exposure levels found decreased brain size in the frontal region and altered white matter architecture, which could result in lower efficiency of neuron signal transmissions.

Even so, the exact ways that lead affects child, adolescent and adult brain function is not clear. Brain chemicals are critical for neurons to function, but little is known about whether lead exposure in childhood changes brain chemical levels to alter brain function.

What did they do?

The researchers examined brain structure and chemicals in 159 young adults aged 19-23 years old using MRI and a newly developed method called proton magnetic resonance spectroscopy (MRS). The participants were part of a large birth cohort study – The Cincinnati Lead Study – with detailed measures of blood lead levels since birth.

The brain imaging scans determined chemical levels in seven different brain regions, including both gray and white matter. Gray matter indicates neuron health and white matter shows if certain protective neuron covers that help transmit signals – called myelin sheaths – developed correctly.

The major chemicals examined were N-acetyl aspartate and cholines. Lower levels indicate dysfunction of neurons and axons – the projections that carry signals away from the nerve cell. The researchers analyzed the association between childhood lead levels and brain chemical levels in a statistical model that took into account other relevant factors, such as age at brain imaging scan and intelligence quotient (IQ).

What did they find?

The participants' average blood lead level during childhood was 13 micrograms per deciliter (µg/dL), which is considered moderate and about 10 times higher than the current average blood lead level in U.S. children today. It is also higher than the 10 µg/dL level of concern set by the Centers for Disease Control that prompts intervention. During adolescence, their average blood lead levels decreased to about 3 µg/dL.

Associations were found in five of the seven brain areas analyzed – three gray matter regions and two white matter regions.

The adults with higher average blood lead levels during childhood had lower levels of brain chemicals in their gray matter, particularly the basal ganglia – a group of compact clusters of neurons at the base of the large region of the brain – and in the cerebellar hemisphere – called the little brain. The basal ganglia controls movement, emotion and cognition. The cerebellar hemisphere is mostly in charge of balance and motor control, but may also affect cognition.

Some white matter regions of the brain also had lower choline and other chemical levels in adults who had higher childhood lead levels. This indicates that both gray matter and white matter are possible targets of lead exposure in human brains.

Most associations persisted after adjustment for age at the time of the brain imaging scan and IQ. This suggests that lead exposure in childhood may cause irreversible changes of brain chemicals in adults. 

The association between childhood blood lead levels and brain chemical concentrations cannot be explained only by IQ deficits from lead exposure. 

However, there was no statistically significant association between lead exposure levels and frontal brain region gray matter, which is mostly involved in high level thinking, planning, organizing and decision making.

What does it mean?

This study provides strong evidence that childhood lead exposure is associated with lower brain chemical levels in regions of the adult brain that control intelligence, behavior and motor function. 

The results indicate long-term change in neuron function and suggest lead can permanently change the myelin that covers and protects the neuron projections that transmit brain signaling messages. There is evidence that both gray and white matter are affected. The association is not limited to a specific region of the brain, suggesting widespread adverse effect of lead on different brain regions.

The study findings are consistent with previous human research of a spectrum of deficits that may be caused by lead exposure in children. These include lower IQs, violent behavior, motor skill problems and attention disorders. The changes to the brain chemical level found in this study may be behind these cognitive and behavioral deficits identified in lead-exposed children.

The change in brain chemicals in the young adults of this study is not considered to be a clinical health problem. That is, a physician would not be able to detect symptoms or diagnose a disease. However, even small changes in brain function can cause extra cost to society, including decreased productivity and creativity, increased disruptive behaviors and higher health care costs.

Although this study did not confirm an association between lead exposure and chemical level changes in frontal region gray matter, prior studies do indicate a loss of brain size in this region. The decreased brain size may mean cell death or shrinkage in this region rather than the changes in metabolism and chemical levels.

This study has advanced the current knowledge of the ways lead affects brain function. Additional research is needed to characterize levels of more chemicals, especially the signal chemicals called neurotransmitters, as well as other regions of the brain.

Lead is still found in many U.S. buildings, in consumer products and is released through industrial processes. Preventing lead exposure in homes and elsewhere – especially before birth and through childhood – is the best precaution against adverse health effects. 


Bellinger, DC. 2004. Lead. Pediatrics 113:1016-22.

Brubaker, CJ, KN Dietrich, BP Lanphear, KM Cecil. 2010. The influence of age of lead exposure on adult gray matter volume. Neurotoxicology 31:259-66.

Brubaker, CJ, VJ Schmithorst, EN Haynes, KN Dietrich, JC Egelhoff, DM Lindquist, BP Lanphear and KM Cecil. 2009. Altered myelination and axonal integrity in adults with childhood lead exposure: a diffusion tensor imaging study. Neurotoxicology 30:867-75.

Cecil, KM, CJ Brubaker, CM Adler, KN Dietrich, M Altaye, JC Egelhoff, S Wessel, I Elangovan, R Hornung, K Jarvis and BP Lanphear. 2008. Decreased brain volume in adults with childhood lead exposure. PLoS Medicine 5:e112.

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Sanders, T, Y Liu, V Buchner V and PB Tchounwou. 2009. Neurotoxic effects and biomarkers of lead exposure: a review. Reviews on Environmental Health 24:15-45.




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