Childhood deficits in the cerebellum may be linked to adult alcoholism

March 14, 2005

The loss of coordination associated with alcohol intoxication is largely due to a disruption of cerebellar function. Long-term heavy drinking can also cause progressive degeneration of the cerebellum for some alcoholics. Defects in the cerebellum itself, however, have never been considered as a potential cause of alcohol dependence. In a first-of-its-kind study, researchers in the March issue of Alcoholism: Clinical & Experimental Research have found that developmental deficits in cerebellar function - as reflected by measures of motor development in the first year of life - may predict the development of adult alcohol dependence.

"The cerebellum is generally known for its involvement in motor coordination," said Ann Manzardo, research assistant professor at the University of Kansas Medical Center and corresponding author for the study. "It's important for assessing and processing information from your environment, and sequencing motor commands so that you can coordinate your movements, making them smooth and orderly. A relatively new line of research has also implicated the cerebellar vermis - the midline portion of the cerebellum - in the regulation of behavior."

"Only recently has the cerebellum's potential involvement in any psychopathology been considered," added Barry Liskow, professor of psychiatry and behavioral sciences at the University of Kansas Medical Center. "For example, imaging studies have suggested the involvement of the cerebellum in schizophrenia. However, there have to my knowledge been no studies that have suggested a role for the cerebellum in alcohol dependence."

Manzardo's research was prompted by a visiting Harvard scholar who, while discussing the cerebellar vermis, suggested that the impaired ability to integrate cognitive and emotional behavior that is associated with cerebellar dysfunction may give an individual characteristics that could make them vulnerable to addiction problems. "Someone having problems coordinating these functions," said Manzardo, "might be inclined to act on their emotional impulses without thinking about the consequences. That's generally what we see in people with alcoholism and other addiction disorders."

Since the cerebellum is an important structure for movement, Manzardo hypothesized that if deficits in the cerebellum were indeed contributing to a person's risk for developing alcoholism, then researchers might be able to identify impairments in motor coordination as "markers" of the risk of developing alcoholism. She was able to access perinatal data collected in a large study of birth defects in Copenhagen, Denmark from 1959 through to 1961. "The original study had more than 9100 babies, with 2500 separate pieces of data collected for each baby; that's a pretty profound piece of research," she said.

The Danish Longitudinal Study on Alcoholism has revisited its participants 20, 30 and 40 years later. Of the subgroup used in this study, two thirds of the original subjects were sons of fathers with a history of alcoholism; one third consisted of sons of fathers with no history of alcoholism. Of the original 330 babies, 241 completed the 30-year follow-up assessment used in this study. Researchers examined motor development measures that included muscle tone at birth and at day five, as well as one-year evaluations of sitting, standing and walking abilities.

Several measures of childhood motor development significantly predicted alcohol dependence at 30 years of age: deficits in muscle tone five days after birth, delays in the age to sitting, and delays in the age to walking.

"The key finding is that infants who exhibit a subtle delay in motor coordination appear to be at increased risk for developing alcoholism later in life," said Liskow. "This motor problem may or may not be related to the cerebellum. However, combined with suggestions that the cerebellum may be involved in the coordination of emotional and cognitive functions as well as motor functions, this finding opens the door for exploring whether development delays or other insults to the cerebellum are related to the development of alcoholism."

"The motor coordination deficits that we found were minor deficits," added Manzardo. "The subjects were not disabled or impaired in any way, they were just consistently lagging in several important benchmarks. Since the study involved primarily high-risk men, we can't be certain how well this will translate to the normal population. I certainly don't want to scare people who might think if their child isn't walking at one year, that he's going to become an alcoholic. All this study does is provide some preliminary evidence that developmental factors related to the cerebellum may also be associated with the later development of alcoholism."

"The most practical implication of this research is that studies in the future which assess the predictors for the development of alcoholism should include data about psychomotor - especially cerebellar - functioning in their subjects," said Liskow.

Manzardo concurs. "The most important contribution that I think this study can make is to shift the emphasis of research in the field, bringing attention to early childhood development as a potentially key factor in the development of alcoholism," she said. "Perhaps we should also focus more intently on the welfare of children. It's possible that allowing children to live in poverty, or stressful and/or abusive environments could be contributing in a physical way to their vulnerability to becoming alcoholics. These kinds of negative life circumstances have always been identified with addictive disorders for their psychological effects, such as learned responses or coping mechanisms. However, this evidence suggests that some of these factors may be exacting real physical changes in the brain that place at least some people at increased risk."
Alcoholism: Clinical & Experimental Research (ACER) is the official journal of the Research Society on Alcoholism and the International Society for Biomedical Research on Alcoholism.

Co-authors of the ACER paper, "Developmental Differences in Childhood Motor Coordination Predict Adult Alcohol Dependence: Proposed Role for the Cerebellum in Alcoholism," were: Elizabeth C. Penick, Elizabeth J. Nickel, Sandra Hall, and William F. Gabrielli of the Department of Psychiatry and Behavioral Sciences at the University of Kansas Medical Center; and Joachim Knop of The Institute of Preventive Medicine in Copenhagen, Denmark.

Alcoholism: Clinical & Experimental Research

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