Alcohol and the Developing Brain

by National Institute of Health

One of the distinguishing features of prenatal alcohol exposure is impaired cognitive and behavioral function resulting from damage to the central nervous system. Information available from the small number of autopsied cases in humans indicates that the offspring of mothers who abused alcohol during pregnancy have various neuroanatomical alterations ranging from gross reductions in brain size to cellular alterations. Recent neuroimaging technology provides the most powerful tool for assessing the neurotoxic effects of fetal alcohol exposure in living organisms and for exploring the relationship between behavioral dysfunction and brain damage at the regional level. Recently, animal research has suggested that the damaging effects of alcohol exposure during brain development could be prevented or attenuated by various pharmacological manipulations or by complex motor training. These promising findings provide directions for developing future prevention or intervention strategies.

Prenatal alcohol exposure adversely affects the developing anatomical structures of the body and brain, leading to a range of physical, cognitive, and behavioral effects. The term "anatomical structures" encompasses both the components of the major body systems (heart, blood vessels, bones, muscles) and the cellular and molecular structures within these major components. Any alterations to the body's anatomical structures, regardless of the level at which they occur (gross or microscopic), may negatively affect an organism's function. This article reviews changes in brain anatomy (neuroanatomy) that occur following developmental (prenatal and/or early postnatal) alcohol exposure in both humans and animal models. It also discusses promising techniques to prevent or reverse alcohol-induced neuroanatomical changes.

The most serious consequence of prenatal alcohol exposure is a constellation of symptoms known as fetal alcohol syndrome (FAS). The criteria for diagnosing FAS include facial dysmorphology, growth retardation, and central nervous system (CNS) dysfunction. Facial dysmorphology results from anatomical changes occurring during weeks 4 to 8 of gestational development that affect how tissues merge under the facial prominences. Of all anomalies associated with FAS, growth retardation is the most obvious form of anatomical change. People who are not professionally trained to analyze facial dysmorphology can easily recognize this anomaly because the weight and size of FAS infants are distinctly smaller than normal. Anatomical alterations associated with CNS dysfunction may range from gross reduction in brain volume (microencephaly), to deficits in cell number in a particular brain region, to cellular modifications of individual nerve cells (neurons), to alterations in the communications among cells. These alterations can have a long-term detrimental impact on behavioral and cognitive development.

Human Neuroanatomical Studies

Since FAS was defined several decades ago, researchers have learned a significant amount about the nature of the behavioral, cognitive, and physical features of FAS and related diagnoses. Until recently, not much was known about the actual anatomical injury to the brains of children with FAS and the relationships between risk factors and behavioral/cognitive outcomes and brain injury. This information could only be acquired at autopsy, and because FAS generally is not life threatening, there were few cases available for study. Researchers had to use caution when reviewing the autopsy data derived from children with FAS who died for reasons other than accidents because brain tissues may be severely affected by other life-threatening diseases. Therefore, researchers had to rely on animal models to address most of these questions. Now that magnetic resonance imaging (MRI) and functional MRI (fMRI) are available for use with living subjects, researchers are generating new data that can lead to a better understanding of brain and behavior relationships in humans, as well as a better interpretation of findings from animal studies. This new information will guide researchers working with animals in their attempts to target mechanisms and potential therapeutic interventions for humans.

Microcephaly

Microcephaly is defined as having a small head relative to body size and is based on the ratio of body weight to head circumference or height-to-head circumference (not to be confused with microencephaly, which refers to the size of the brain). Early studies showed that microcephaly was related to alcohol use throughout pregnancy. Coles reported that children whose mothers stopped drinking before the end of the second trimester had larger head circumferences on average than children whose mothers continued to drink throughout pregnancy. This finding suggests that a pregnant woman may be able to avoid additional injury to her baby's brain if she stops drinking before the third trimester. These data are useful for counseling pregnant women about the benefits to their unborn children of reducing or ceasing their alcohol consumption as soon as their pregnancy is identified.

Neuroimaging

In recent years, researchers have used both anatomical MRI and functional MRI to determine the nature of brain injury in living offspring with FAS. Early seminal MRI studies by Riley and colleagues showed reductions in the volume of several brain regions in children who were affected by heavy1 maternal drinking. (1 Heavy drinking is defined as 7 to 13.99 ounces [oz] absolute alcohol per week or 14 to 27.9 standard drinks per week. These studies were significant because they showed a reduction in the size of specific brain regions independent of any reduction in total brain volume.

More recently, Archibald and colleagues found that, in children with FAS, the fibers carrying information between brain cells (white matter) appear to be more susceptible to reductions in volume than the outer, convoluted layer of brain tissue called the cerebral cortex. Within the cerebral cortex, the parietal lobe (situated at the upper middle of the cerebrum) is reduced by prenatal alcohol exposure, whereas the temporal and occipital lobes (located on the sides and back of the brain, respectively) are not. These anatomical data clearly show that alcohol's effect on the developing brain is not uniform but varies depending on the brain region. Wass and colleagues used ultrasound sonography to examine living fetuses exposed to alcohol and found a reduction in the size of the frontal cortex, but not other cortices, of the cerebrum.

Clark and colleagues used MRI to examine the brains of adults who had been exposed to alcohol in utero and were classified as nonretarded. They found only one abnormal case, a thinning corpus callosum in the adult with the lowest IQ. (The corpus callosum is a bundle of fibers through which the two cerebral hemispheres communicate.) Otherwise, the MRIs of all other study participants were considered to be in the normal range. Some of the participants from this study were examined further using positron emission tomography (PET). These scans revealed changes in metabolic rate in the thalamus and the head of the caudate nucleus (two brain structures important for communication within the brain). The authors suggest that the functional findings may be related to the regional vulnerability of the brain to prenatal alcohol exposure, which is consistent with the conclusion of an earlier PET study.

More recently, Bookstein and colleagues explored the relationship between the shape of the corpus callosum in adolescents and adults exposed to alcohol prenatally and the degree of their cognitive impairment, to see if the shape of the corpus callosum was an indicator of heavy in utero alcohol exposure. Although the volume of the corpus callosum in the alcohol-exposed study participants was not different from that in the control participants, the variability in the shape of the corpus callosum was much higher in the alcohol-exposed group. The authors suggest that variations in corpus callosum size, volume, and shape revealed by MRI can be used as diagnostic criteria for FAS and related brain disorders. Thus, MRI could be used to solicit more social support services, which often are lacking for adolescents and adults affected by prenatal alcohol exposure.

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