Genetics may predict risk for relapse among alcohol-dependent patients

Feb 3 2009

In Poland, alcohol dependence (AD) affects about four percent of the population, causing about 10,000 deaths per year.

While a number of biological markers have been linked to a predisposition for developing AD, a new study has found a link between the Val66Met (rs6265) polymorphism in the brain-derived neurotrophic factor (BDNF) gene and risk for post-treatment relapse among AD patients.

Results will be published in the April issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.

"Some people are simply more likely than others to become dependent on alcohol," explained Marcin Wojnar, associate professor of psychiatry at the Medical University of Warsaw and adjunct researcher at the University of Michigan. "Clearly, cultural, social, and psychological factors are involved. AD also runs in families, so there is an inherited component to it. Once AD has developed, certain people are more likely to relapse after treatment than others. Some studies show that a family history of alcoholism can lead to a more severe illness that is harder to treat, which is why our group and others are looking at genetic factors."

"Although some biological predictors of the re-emergence of AD have been described," said Lance Bauer, professor of psychiatry at the University of Connecticut School of Medicine, "biological measures can be affected by many variables, such as the time of day; the patient's gender, age, or medical background; or medications that have been prescribed. Most genetic differences are not complicated by these same variables. Accordingly, this study by Wojnar and colleagues points us toward a new and promising approach."

"We selected genetic polymorphisms that were, one, related to serotonin or dopamine function; and two, associated with suicidality and/or impulsivity," said Wojnar, who is the study's first author. "Serotonin's decreased functioning has consistently been reported to be associated with both impulsivity and suicidal behaviors. Regarding dopamine, most researchers agree that it plays an essential role in addiction, either by causing pleasure from taking drugs or by telling the brain to associate that pleasure with certain cues in the environment."

The researchers examined 154 patients (117 males, 37 females) from addiction-treatment programs in Poland who met Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition criteria for AD. All were assessed for demographics, severity of alcohol use, suicidality, impulsivity, depression, hopelessness, and severity of alcohol use at baseline; 123 patients were followed for approximately one year to evaluate treatment outcomes. In addition, patients were tested for genetic polymorphisms in several genes as predictors of relapse – defined as "any drinking during follow-up" – which were: rs1386483 in the tryptophan hydroxylase type 2 gene, C102T (rs6313) in the serotonin receptor 2A gene, 5-HTT gene-linked polymorphic region in locus SLC6A4, C(-1019)G (rs6295) in the serotonin receptor 1A gene, Val158Met (rs4680) in the catechol-O-methyl transferase gene, and the Val66Met (rs6265) in the BDNF gene.

"Our study indicated that some patients may have inherited a tendency to return to drinking even after intensive treatment," said Wojnar, "and [may be] more treatment-resistant than other patients. Specifically, we found that a particular type or variant of the gene that codes for BDNF was associated with an increased risk for relapse in alcoholic patients, particularly those with a family history of AD." BDNF is a protein found in the brain that helps nerve cells survive and connect to one another.

"These findings provide further support for the assertion that alcoholic patients are not all alike," said Bauer. "Some possess genetic propensities which … may motivate or promote risk for alcoholism as well as risk for treatment failure."

"These patients may have special difficulty in responding well to currently available treatments because of their biological makeup," added Wojnar, "and therefore may need newly constructed intensive programs of therapy that are preferably individualized. This might be a step forward towards 'personalized medicine.'"

Bauer agreed. "During the past 10 years, several new treatments have become available," he said. "However, 'how does one decide among the options?' Genetic differences may eventually help us make the decision. For example, individuals possessing the high-risk-for-relapse variant of the BDNF gene might warrant assignment to the most intensive – and usually most expensive – treatment. Individuals with the low-risk variant might not require this level of treatment to have a good outcome."