Individual differences in alcohol response – ranging from sleepy to social, sad to happy – have a tremendous influence on a person's risk for developing alcohol dependence. Researchers already know that many of the psychological, physiological, and behavioral effects of alcohol are determined by the central nervous system and related neurotransmitter activity, although beliefs about the effects of drinking alcohol are also important. Symposium proceedings published in the February issue of Alcoholism: Clinical & Experimental Research present evidence for how genetic variation may influence neurotransmitter activity, thereby having an effect on alcohol sensitivity and subsequent behaviors.
"Activities of neurons, which are specialized cells of the nervous system, influence the release of neurochemicals that cause increases or decreases in brain activity," said Kim Fromme, symposium organizer and associate professor of psychology at The University of Texas at Austin. "Virtually everything we think, feel, sense, and do are determined by activity of these neurochemicals and their related neuronal activity in the brain. Approximately 100 different neurochemicals have been identified, and many of them have been found to be affected by alcohol." Four presentations were given during the symposium at the June 2003 Research Society on Alcoholism meeting in Fort Lauderdale, Florida. Presenters combined human genotyping with laboratory measures of behavior and subjective reports in order to "match" individuals' genetic makeup with the behavioral effects that people experience and exhibit due to alcohol. Some of the key points were:
Activity of the dopaminergic and GABAergic neurotransmitters appear to underlie the stimulant and sedative effects of alcohol, respectively.
"Neurotransmitters can be classified in three ways," said Fromme, "excitatory, which means they increase brain activity; inhibitory, which means they decrease brain activity; or modulatory, which means they don't act directly on brain activity but rather influence other neurotransmitters. Dopamine has been classified as both an excitatory and a modulatory neurotransmitter, which means that it tends to increase brain activity, especially when related to pleasure seeking and exploration. As indicated by these findings, dopamine is thought to possibly underlie the stimulant effects of alcohol. GABA, on the other hand, is an inhibitory neurotransmitter. When activated by alcohol, GABA is thought to contribute to the anxiety reduction and relaxation many people experience from alcohol."
Two of the symposium participants presented contradictory findings regarding the role of a polymorphism of the serotonin transporter gene, SLC6A4, in subjective response to alcohol and associated risk for alcohol dependence.
One study found that individuals with the short form of the SLC6A4 allele demonstrate a low level of response to alcohol, which supports previous research showing that the S allele may be associated with a greater risk for alcohol dependence.
In contrast, other research indicates there is no reliable association between the SLC6A4 genotype and subjective response to alcohol. In fact, the L allele of the serotonin polymorphism was associated with a more rapid adaptation to alcohol effects (referred to as "acute tolerance") over time.
"These contradictory findings are perplexing," said Fromme, "but may relate to the populations studied, to variation in the laboratory methods used to assay the genetic material, or to neurotransmitters that interact with SLC6A4 and vary among different people and have yet to be measured."
An investigation of aldehyde dehydrogenase and alcohol dehydrogenase genetic variants and their association with the alcohol-related flushing response that is prevalent in Asian populations suggests that increased sensitivity to alcohol is the mechanism by which these alleles combine to protect against alcohol dependence.
"Previous studies have shown that aldehyde dehydrogenase and alcohol dehydrogenase contribute to the metabolism of consumed alcohol into its natural and safe components," said Fromme. "If individuals have an impaired ability to metabolize alcohol, via alterations in either of the dehydrogenases, they can have a negative physiological response to alcohol, such as flushing or nausea. This reaction might protect the individual from continuing to drink at a rate that would lead him or her to develop alcohol dependence."
Fromme added that the symposium presentations, while still in the infancy stage of research on biological and behavioral markers of alcohol sensitivity, represent a crossing of the divide between animal and human research.
"We can now easily obtain genetic material from humans, via blood draw or cheek swab, and we now have advanced methods for analyzing these samples," she said. "This allows us to match the behavioral effects a person exhibits and experiences from alcohol with their genetic makeup. Prior to these developments, we were only able to match biology and behavior in animals and then extrapolate to humans. The number of potential neurotransmitters that may influence individual response to alcohol is large," she added, "and we have only begun to understand the relations among neurotransmitter activity, individual responses to alcohol, and alcohol-use patterns among people."
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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