Sober N Clean

Variations in the genetic makeup of alcoholics may affect how much they drink, a new study suggests. And the key might be the brain's control of serotonin, a mood-influencing neurological chemical.

The research could potentially help doctors understand who might be at highest risk of becoming an alcoholic, and then treat that person, said study co-author Ming D. Li, head of neurobiology at the University of Virginia.

Li added that the research is unique, because it shows that a single gene variation is connected to a kind of behavior -- alcoholism.

The genetic blueprint that people inherit from their parents accounts for an estimated 40 percent to 50 percent of a person's risk of becoming alcoholic, said Dr. Robert Philibert, director of the Laboratory of Psychiatric Genetics at the University of Iowa.

The interplay between genetic makeup and environmental factors is responsible for the rest of the risk, said Philibert, who's familiar with the new study's findings.

"This study really takes the next step down the line," he said, in understanding the role that genes play in alcoholism.

For the study, the researchers looked at the DNA of 275 alcoholics who had sought treatment. Almost 80 percent were men, and all were of European descent. The researchers found that differences in the genes that affect serotonin levels in the brain coincided with the amount of alcohol consumed by the drinkers.

The findings were published online Nov. 20 and were expected to be in the February 2009 issue of Alcoholism: Clinical & Experimental Research.

Scientists think serotonin, a neurotransmitter, is crucial to human moods and emotions as well as things like sleep. Low levels of serotonin can lead to depression; some antidepressants aim to help the brain do a better job of processing serotonin.

"We know that serotonin is critical to maintaining a positive sense of self and for controlling our anxiety," Philibert said. That could explain a possible connection between serotonin levels and alcoholism, he added.

Li cautioned, however, that it's unlikely that a single genetic trait by itself would make someone more susceptible to alcoholism. It's more likely that a genetic variation works with other genes to raise the risk, he said.

Philibert said research might lead to a day when doctors could look at an alcoholic's genetic traits and discover whether antidepressants could help that person.
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source: U.S.News & World Report

The influence of genetics increases as young women transition from taking their first drink to becoming alcoholics. A team of researchers at Washington University School of Medicine in St. Louis found that although environment is most influential in determining when girls begin to drink, genes play a larger role if they advance to problem drinking and alcohol dependence.

The researchers studied 3,546 female twins ages 18 to 29 to ferret out the influences of genes and environment in the development of alcohol dependence. Their findings appear in the April issue of Alcoholism: Clinical & Experimental Research.

The road to alcohol dependence involves transitions through many stages of drinking behaviors: from the first drink to the first alcohol-related problems (such as drinking and driving, difficulty at school or work related to alcohol use) to alcohol dependence.

Environmental factors the twins shared, such as exposure to conflict between parents or alcohol use among peers in school, exerted the largest influence on initiation of alcohol use. The study found that females who had their first drink at an earlier age were more likely to develop serious alcohol problems. The researchers found that all transitions were attributable in part to genetic factors, increasing from 30 percent for the timing of first drink to 47 percent for the speed at which women progressed from problem drinking to alcohol dependence. But genetics did not explain everything.

"Even when genetic factors are most influential, they account for less than half of the influence on drinking behavior," says lead author Carolyn E. Sartor, Ph.D., a postdoctoral research fellow at the School of Medicine. "That's good news in terms of modifying these behaviors and reducing the risk of developing alcohol dependence. Genetics are not destiny, and our findings suggest that there are opportunities to intervene at all stages of alcohol use."

Sartor's team collected alcohol-use histories from telephone interviews to determine when these women made transitions from one drinking milestone to the next. They studied twins to get an idea of the genetic influences on those transitions. Identical twins share 100 percent of their genetic material, and fraternal twins share about half. So when identical twin pairs are found to be more similar on a given behavior than fraternal twin pairs, this suggests that genetics are playing a role in that behavior. The researchers used this twin-based design to estimate the contributions of genes-versus-environment to the rate at which women progressed through stages of alcohol use.

"Alcohol dependence is a psychiatric disorder, but drinking alcohol in moderation is normative and is a part of many cultural traditions," Sartor explains. "For example, 85 percent of women in our study reported having at least one drink in their lifetimes whereas only about 7 percent became alcohol dependent."

Past studies have focused more on men than women, but Sartor says it is important to study both sexes because risk factors that contribute to alcohol problems differ somewhat between males and females. She also says this study helps to dispel the myth that alcohol dependence is a disorder exclusive to middle-aged men. In the United States, the prevalence of alcohol use disorders is highest among 18- to 29-year-olds.

"Much of the heavy drinking that occurs in the young adult years is actually problem drinking," she explains. "What once was perceived as partying a little too much is now being recognized as a potentially serious problem."

The majority of the young women in the study curtailed their drinking before it advanced from a normal behavior to a psychiatric disorder.

The researchers plan to extend their investigations to examine genetics and environment on other drinking behaviors, such as the cessation of alcohol use. Many problem drinkers in their 20s, for example, "mature out" of alcohol-related problems, she says. These changes coincide with major lifestyle changes including engagement in serious relationships, commitments to career and the arrival of children, all of which involve significant changes in the environment. Sartor and her colleagues also are planning to study the timing of transitions in the development of other substance-use problems.

source: MediLexicon

Authors say research supports notion that addiction is a disease

Drug or alcohol abusers who relapse, even after long periods of abstinence, are often reviled as too weak or undisciplined to straighten themselves out.

But a UNC Chapel Hill psychologist has found evidence that suggests, in fact, that addicts' brains may be wired in a way that makes them more prone to give in to temptation.

The research, published in the December issue of the Journal of Neuroscience, provides further evidence that addiction is a disease, not a character flaw, says Charlotte Boettiger, an assistant professor of psychology at UNC and lead author of the paper released Tuesday.

"It wasn't that long ago that we believed schizophrenia was caused by bad mothers and depression wasn't a disease," Boettiger said. "Addiction is maybe just a couple of decades behind."

What they did: Boettiger and colleagues peeked inside the brain to see how brain function might be different in a substance abuser.

The study, conducted while Boettiger was at the University of California at San Francisco, used imaging technology to take pictures of sober alcoholics' and nonalcoholics' brains as they chose between immediate and delayed rewards. Alcoholics chose the quick payoff almost three times more often.

What they found: Scans showed that the most impulsive subjects -- most but not all of whom had a history of alcoholism -- had reduced activity in an area of the brain that helps assess rewards and increased activity in other sections of the brain associated with judgment and decision-making. The differences suggest that some addicts may have impaired ability to think through a decision, Boettiger said. Blood tests implicated a variant gene.

What it means: More study is needed, but Boettiger said the findings suggest new treatment approaches for addiction. Drugs for early-onset Alzheimer's disease and Parkinson's disease target the same regions of the brain, so those medicines may also be useful for alcohol or drug addiction.

source: JEAN P. FISHER
(Raleigh) News & Observer
http://www.charlotte.com/

A variant of a gene involved in communication among brain cells has a direct influence on alcohol consumption in mice, according to a new study by scientists supported by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health (NIH), and the U.S. Army.

Scientists do not know yet whether a similar gene variant, with a similar effect on alcohol consumption, exists in humans.

Known as Grm7, the gene encodes a receptor subtype that inhibits the release of glutamate and other neurotransmitter molecules that brain cells use to communicate with one another. Researchers identified a gene variant, or polymorphism, that reduces the abundance of Grm7 messenger RNA (mRNA) in brain tissue. mRNA is the molecular intermediate between a gene and its protein product. Mice that possess this gene variant drink more alcohol than do mice with higher brain levels of Grm7 mRNA. A report of the study appears as an online Article in Press in Genomics.

“This is a noteworthy contribution, particularly since identifying genes that predispose to alcohol-related behaviors is such an arduous task,” says NIAAA Director Ting-Kai Li, M.D.

Scientists have long known that genes account for a significant proportion of the risk for alcoholism. However, the fact that there are multiple such genes that interact with each other and with multiple environmental factors to influence drinking behavior has hampered studies aimed at isolating individual genes.

“Controlling for this background noise -- the various gene-gene and gene-environment interactions -- presents considerable methodological challenges,” notes first author Csaba Vadasz, Ph.D., professor of psychiatric research in the department of psychiatry at New York University School of Medicine, and Director of the NeuroBehavioral Genetic Research Program at the Nathan Kline Institute in Orangeburg, N.Y.

To overcome these difficulties, Dr. Vadasz and colleagues applied a variety of genetic and analytic techniques to animals having nearly identical genetic background, but differing in their preference for alcohol, to identify a chromosomal region, and ultimately the Grm7 gene, associated with alcohol preference.

“Our findings support emerging evidence of the critical role that the brain’s glutamate pathways play in addiction,” says Dr. Vadasz. “While dopamine has traditionally been cast as a central actor in the neurochemistry of substance use and abuse, recent studies indicate that glutamate systems play an important role in reinforcement and addiction.”

If further studies show that a similar gene variant is relevant to alcohol problems in humans, the finding by Dr. Vadasz and colleagues may lead to new opportunities for developing drugs to treat alcohol dependence. Dr. Vadasz speculates that such drugs might be designed to control the level of the Grm7 gene product or modulate the activity of the gene product itself.

source: http://www.scientificblogging.com