"I think the early detection of alcohol abuse is a higher priority in Northern Europe than in Eastern Europe, or in the developing countries, where it has no priority," said R. Adron Harris, director of the Waggoner Center for Alcohol and Addiction Research at the University of Texas at Austin and corresponding author for the proceedings. "The U.S. has a grass-roots movement to detect and prevent drunk driving, but there is not enough emphasis on more general detection of alcohol abuse."
Harris added that the use of emerging biomarkers that utilize genomic and proteomic advances, especially in conjunction with questionnaires and other laboratory tests, is vital for the early detection of alcohol use and abuse as well as the ability to measure compliance following treatment for alcohol dependence.
Key presentation highlights included:
- Medical screening of all patients is not an efficient method for reducing dangerous drinking. A more cost-effective approach would be to analyze the patient's clinical signs, followed by a judicious use of questionnaire tools and blood tests whenever suspicion arises.
"Current methods that consist mainly of self reporting and screening for severe liver damage do not detect most cases of alcohol abuse," said Harris, "and a sensitive and specific test is needed."
- Biological markers – such as carbohydrate-deficient transferrin (CDT), gamma-glutamyl transferase (GGT), a urinary derivative of serotonin (5-HTOL/5-HIAA), mean corpuscular volume (MCV) of red cells, aspartate aminotransferase (ASAT), and alanine aminotransferase (ALAT) – have been used to monitor patients' drinking outcomes following treatment for alcoholism. But none of these are ideal biomarkers for alcohol abuse.
"Current biomarkers lack sensitivity and selectivity," said Harris, "so it is essential that we develop a new generation of biomarkers for alcohol dependence as well as other brain diseases."
- Obtaining high-quality ribonucleic acid (RNA) from human whole blood samples, and using it for microarray analysis, may allow for differential gene expression that can be used to identify candidate biomarkers in alcoholics.
"All cells in the body respond to their surroundings," explained Harris, "whether they be nutrients, toxins or alcohol - by turning on or off specific genes. Thus, the pattern of gene usage or the 'RNA message' – analogous to the pattern of lights on and off in an office building – can tell us about the experience of the cells. In the alcohol abuser, blood cells are bathed in alcohol and we can see this. The problem is one of complexity: every cell has about 30,000 genes and a complete picture of activity requires measurement of all genes. Fortunately, this is now possible with 'gene chips' or DNA microarrays, which allow investigators to select the RNA messages that provide a unique signature for alcohol abuse."
- As part of many European drunk-driving programs, CDT is used – usually in conjunction with GGT and other biomarkers – to confirm abstinence or detect relapse prior to reissuing previously withdrawn drivers' licenses.
"When there finally is an accurate biomarker for alcohol abuse, it will be interesting to see where society feels use of this test is warranted and where it is intrusive," observed Harris. "Drug testing is now routine for many jobs, and is a condition of employment for performance-sensitive areas such as airline pilots, ship captains, etc. Testing for alcohol biomarkers is also required prior to restoration of a medical license after alcohol problems. However, I am not sure if this practice will become acceptable prior to restoration of driving licenses after a DWI offense. Perhaps it will be one option, that is, 'attend an alcohol program regularly or submit to regular biomarker testing.'"
Harris added that biomarker developments discussed at the symposium are critically important for a number of reasons: early detection makes it that much easier to treat alcohol problems before they become dependence issues; biomarkers can help to make adherence to abstinence that much more likely; and new discoveries can help to ensure that new therapies for alcoholism are working.
"For the average reader," said Harris, "there may be concern that such tests will limit the use of a legal substance and interfere with one's right to imbibe. This is, of course, an oversimplified view. First, alcohol is not legal for those under 21 years of age and intoxication is not legal in many circumstances. By analogy, tobacco is legal for those older than 21, but there are many restrictions on its use and employers have the right to restrict smoking. What people need to remember," he added, "is that misuse of alcohol will harm an individual's health, and these new advances are designed to be used to help people who either are not aware that they are at risk or deny their problem drinking."
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/presenters of the symposium proceedings published in the ACER paper, "Revealing Alcohol Abuse – to Ask or to Test?," were: Christer Alling of the Department of Laboratory Medicine at Lund University Hospital in Sweden; Jonathan D. Chick of the Department of Psychiatry of the University of Edinburgh; Raymond Anton of the Center for Drug and Alcohol Programs at the Medical University of South Carolina; R. Dayne Mayfield of the Waggoner Center for Alcohol and Addiction Research at The University of Texas at Austin; Mikko Salaspuro of the Research Unit of Substance Abuse Medicine at the University of Helsinki; and Anders Helander of the Karolinska Institute, as well as the Alcohol Laboratory at University Hospital in Stockholm. The study was funded by the National Institute on Alcoholism and Alcohol Abuse.