Alcohol and the developing brain: neuroanatomical studies

Alcohol Research & Health, Spring, 2003 by Wei-Jung A. Chen, Susan E. Maier, Scott E. Parnell, James R. West

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. KEY WORDS: prenatal alcohol exposure; neuroimaging; neurotoxicity; fetal alcohol effects; brain damage; cognitive development; AODR (alcohol and other drug related) behavioral problem; prevention strategy; drug therapy; CNS function; cell adhesion molecules; mitochondria

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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 (e.g., 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 (i.e., 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 (i.e., microencephaly), to deficits in cell number in a particular brain region, to cellular modifications of individual nerve cells (i.e., 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 (Ernhart et al. 1985; Rosett et al. 1983). Coles (1994) 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.