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National Institute on Drug Abuse - NIDA NOTES
Research Findings
Volume 16, Number 4 (October 2001)

Biochemical Brain Abnormality Found in School-Age Children Prenatally Exposed to Cocaine

By Robert Mathias, NIDA NOTES Staff Writer

Exposure to cocaine before birth may affect the way a child’s brain functions many years later, according to a recent NIDA-funded study. The brain-imaging study found a chemical abnormality in the brains of 8-year-old children that may reflect alterations in metabolic processes that enable brain cells to use energy and function properly, the researchers say.

“These children were exposed to cocaine only during gestation and their brains have had 8 years to recover from that exposure,” says Dr. Joseph Frascella of NIDA’s Division of Treatment Research and Development. “It is surprising that they are still showing these deficits so many years later.” The new finding suggests that early exposure to drugs has more long-lasting effects on the brain than previously thought, he notes.

The nature and extent of possible developmental damage to infants and children from prenatal exposure to cocaine has been the subject of much apprehension and scientific study. In the 1980s, anecdotal reports of abnormalities among cocaine-exposed children contributed to fears that these children were irreparably damaged and would never be able to function in society. Subsequent scientific research has dispelled such exaggerated concerns for the vast majority of prenatally exposed children. NIDA-funded studies that have been tracking the development of groups of cocaine-exposed babies through adolescence now indicate that most seem to function normally, but some may have subtle impairments in their ability to control emotions and focus attention that could put them at risk of behavioral and learning difficulties.

Previous brain-imaging studies of children prenatally exposed to cocaine have yielded conflicting information about the drug’s effects on the developing central nervous system. Some studies have found abnormalities in brain structure, while others have not. Studies in abstinent adult cocaine abusers, using an imaging technique called magnetic resonance spectroscopy (MRS), have suggested that chronic cocaine use may cause persistent damage to neurons in the frontal lobes of males and that brain metabolic abnormalities also could exist despite a normal-appearing brain structure. Dr. Lynne Smith of the Harbor-UCLA Medical Center in Torrance, California, and Dr. Linda Chang of Brookhaven National Laboratory, in Upton, New York, used this MRS technique to see if similar biochemical abnormalities might be present in the brains of children who had been prenatally exposed to cocaine, even if they appeared to have no structural damage.

The researchers used magnetic resonance imaging (MRI) to assess brain structure and MRS to examine brain biochemistry in 14 8-year-old children who had been exposed to cocaine in the womb. They administered the same brain scans to a control group of 12 age-matched, nonexposed children. The MRS scans measured levels of various chemicals in different brain regions. Increased or reduced concentrations of these chemicals can indicate either damage to nerve cells or alterations in brain cell function in these regions. The researchers assessed a frontal area of the brain, made up of “white matter,” which consists mainly of nerve fibers and specialized support cells. They also looked at an area deep in the brain called the basal ganglia, which contains clusters of nerve cell bodies, or “gray matter.”

The study found no difference between the exposed and nonexposed children in concentrations of N-acetyl-aspartate (NAA), a nerve cell metabolite, in either the frontal area or the basal ganglia. Because NAA levels are markers for the density and integrity of nerve cells, the normal NAA found in children prenatally exposed to cocaine suggests they did not have significant nerve damage or loss in the two brain regions that were examined. The MRI evaluations also showed no brain structure abnormalities in children in either group. However, cocaine-exposed children had significantly higher levels of creatine in the white matter of the frontal lobes than nonexposed children. Elevated creatine levels indicate that the brain cells of cocaine-exposed children use energy differently in this region.

“All brain cells require creatine for all functions,” says Dr. Chang. “The altered creatine levels we found could affect how both nerve cells and support cells are functioning in the brain. We also have found the same abnormal creatine levels in frontal white matter in adult cocaine abusers more than a year after they have stopped using cocaine. The drug seems to have a particularly long-lasting effect on energy metabolism in this brain area that merits further investigation.”

“The frontal area of the brain is involved in our ability to control impulses and sustain attention on a task,” notes Dr. Frascella. Thus, it is possible that the altered brain function found in this area could be a biological basis for findings from other research that some cocaine-exposed children are more impulsive and easily distracted than their peers. However, additional research is needed to make this determination, he says.

• Chang, L.; Ernst, T.; Strickland, T.; and Mehringer, C.M. Gender effects on persistent cerebral metabolic changes in the frontal lobes of abstinent cocaine users. American Journal of Psychiatry 156(5):716-722, 1999.[Abstract]
• Chang, L., et al. Neurochemical alterations in asymptomatic abstinent cocaine users: A proton magnetic resonance spectroscopy study. Biological Psychiatry 42(12):1105-1114, 1997.
• Smith, L.M.; Chang, L.; et al. Brain proton magnetic resonance spectroscopy and imaging in children exposed to cocaine in utero. Pediatrics 107(2):227-231, 2001.

Similar Long-Term Effects Seen From Prenatal Methamphetamine Exposure

Dr. Linda Chang of Brookhaven National Laboratory in Upton, New York, and her colleagues at UCLA-Harbor Medical Center in Torrance, California, have followed up their brain-imaging study of cocaine-exposed children with a preliminary study of school-age children who were prenatally exposed to methamphetamine. The researchers assessed the same chemical metabolites that they had assessed in the brains of cocaine-exposed children.

“The findings in methamphetamine-exposed children were very similar to what we saw with cocaine-exposed children,” Dr. Chang says. “We found the same abnormalities in creatine levels in the frontal white matter, which indicate altered energy metabolism. Unlike the cocaine-exposed children, methamphetamine-exposed children also showed abnormalities of N-acetyl-aspartate (NAA), a marker of nerve cell integrity, similar to those seen in adult methamphetamine and male cocaine abusers,” she says. In the adult studies, the researchers were able to conclude that such NAA levels suggested methamphetamine abuse and cocaine abuse by males could result in damaged or destroyed nerve cells. In the prenatal methamphetamine study, too few children were assessed for the researchers to determine whether the differences in NAA levels between methamphetamine-exposed and nonexposed children were statistically significant.

• Smith, L.M.; Chang, L.; Yonekura, M.L.; Grob, C.; Osborn, D.; and Ernst, T. Brain proton magnetic resonance
spectroscopy in children exposed to methamphetamine in utero. Neurology 57(2):255-260, 2001. [Abstract]


NIDA NOTES - Volume 16, Number 4

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