CONTACT: BECKY SOGLIN
2130 Medical Laboratories
Iowa City IA 52242
(319) 335-6660; fax (319) 335-8034
Release: Sept. 22, 1999
UI study suggests variable effects of fetal alcohol
syndrome on brain
IOWA CITY, Iowa -- Fetal alcohol syndrome in affected
people has been associated with mental retardation and a smaller or nonexistent
corpus callosum. The callosum is a major brain pathway that coordinates input
from one side of the brain to the other to help provide unified sense perception.
However, a study led by a University of Iowa Health Care researcher suggests
that moderate (versus severe) alcohol overexposure can cause the corpus callosum
to be larger than normal.
"Previous research showed that the corpus callosum
is very small or even nonexistent in people with fetal alcohol syndrome,"
said Michael W. Miller, Ph.D., UI professor of psychiatry and pharmacology,
and a career research scientist at the Iowa City Veterans Affairs Medical
Center. "But this human data was quite at odds with other studies, including
one at the UI involving rats, which showed maternal alcohol intake can increase
the number of cells contributing connections passing through corpus callosum
The contradiction motivated Miller and two University
of Washington researchers to investigate how fetal alcohol syndrome affects
the corpus callosum in macaques, primates that closely resemble humans. The
team analyzed 15 post-puberty macaques affected to varying degrees by maternal
alcohol consumption during gestation. The findings were published in the Sept.
13 issue of the Journal of Comparative Neurology.
Using magnetic resonance imaging (MRI) and post-mortem
analyses, the team found that offspring of macaque mothers fed 170 - 270 milligrams
(mg) of alcohol per deciliter of blood (sufficient to bring blood alcohol
concentrations to .17 to .27 mg percent) for several weeks or months had more
axons in their corpus callosums than did control animals. These axons conduct
signals from one side of the brain to the other. In contrast, Miller said,
the research on humans affected by fetal alcohol syndrome was generally based
on extreme cases in which the mothers' blood alcohol levels were closer to
300 mg per deciliter of blood or .30 mg percent blood alcohol level.
"The human data compiled to date has been highly selective
and almost biased to worst-case scenarios," Miller said, referring to the
.30 blood alcohol concentration. "Our findings suggest that moderate alcohol
overexposure causes an increase in the number of axons, whereas high alcohol
overexposure causes a breakdown, thus reducing the size of the corpus callosum."
Miller said human clinical studies under way at other
institutions may confirm this difference between callosal hypergrowth and
"One particularly interesting finding in our study
was that the alcohol overexposure did not increase the entire corpus callosum
but mostly enlarged the rostral portion, the part toward the front of the
head," Miller added. "This portion of the corpus callosum communicates information
between the frontal and parietal cortexes, the brain areas that participate
in movement and touch and in executive functions such as initiating voluntary
movements and other higher-order processing."
Several behavioral studies on children with fetal
alcohol syndrome show that executive functions of the rostral portion are
reduced due to the alcohol exposure.
Miller said that although the primate and human clinical
studies differ on the effect alcohol has on corpus callosum size, the studies
agree that the part most affected is the rostral portion.
He described his findings as "more provocative than
coming up with any solutions." He hopes his study will encourage researchers
conducting human studies to study a range of people affected by fetal alcohol
"There might also be a way of using the MRI analysis
in clinical settings to better see how children are affected," he added. "The
findings could possibly help other researchers find ways for these children
to learn more effectively."
Miller will next investigate callosal projection neurons
to understand the factors that regulate the growth of these cells and how
alcohol exposure affects them.
Miller's co-investigators from the University of Washington
were Susan J. Astley, in epidemiology at the School of Public Health and Community
Medicine, and Sterling K. Clarren, in pediatrics at the School of Medicine.
Miller's work on the study was supported in part by a grant from the federal
Department of Veteran Affairs. All three researchers received grant support
from the National Institutes of Health (the National Institute of Alcohol
Abuse and Alcoholism, and the National Institute of Dental Research). The
University of Washington researchers also received support from General Electric.