1. Some studies support the association between genetic factors and alcohol use disorders (abuse and dependence). Is it possible to determine if alcohol use disorders are caused by genetic or environmental factors, as family and/or peer influence? How can we distinguish between these two factors?
In general, the psychiatric disorders are considered complex and influenced by multiple factors, because they are a result of a complex interaction between genetic and environmental factors. Both of these factors must be present for the development of the disorder. Apparently, studies have indicated that substance use is greatly influenced by environmental factors, such as family or peers environment. On the other hand, the transition to alcohol abuse and dependence seems to be more influenced by genetic factors. This is the reason why some individuals become alcohol dependents and others do not, even under the same environmental conditions.
2. How can the research progress on genetics and alcohol dependence help the development of early interventions? Do you believe that these interventions could reduce significantly the alcohol use disorders?
The identification of the genetic risk factors for alcohol dependence will enable the early detection of risk individuals for this condition, which will allow the use of preventive strategies associated to what we call “genetic counseling”. Thus, this individual can receive better instructions about his risks, therefore avoiding potential health problems. In addition, genomic studies may further improve the diagnosis and point out new targets for pharmacological therapies, which will help the development of more efficient treatments.
3. How can the regulation/expression of several genes influence the risks of alcohol use disorders?
As any other drug of abuse, if it is used regularly alcohol tends to generate symptoms known as tolerance – decreasing in the response intensity and the necessity of consuming a greater amount of the substance in order to feel the same effect obtained before with lower doses. In contrast, the interruption of drugs consumption can cause the withdrawal syndrome, characterized by physical symptoms, such as shivering, cardiovascular alterations and hallucinations; and/or emotional symptoms, as disphoria (unstable mood or affective disturbance) and anhedonia (inability to experience pleasure from everyday life events). Both behavioral phenomena (tolerance and withdrawal syndrome) seem to be at least in part originated from biological/genetic compensatory adaptations that occur during the development of drug abuse and dependence. The nervous system tends to adapt due to the constant presence of drugs in the organism, trying to maintain the natural equilibrium by diminishing or increasing the concentration of some substances (i.e. neurotransmitters and their receptors). In this way, the production of these substances is regulated by the expression of their respective genes.
4. According to your research, there are genetic variants in the promoter region of the alcohol dehydrogenase 4 (an enzyme responsible for the metabolism of alcohol in humans) associated to a greater risk for alcohol dependence. How can this process result in a predisposition for alcohol dependence?
After alcohol ingestion, the greatest part of this substance is metabolized in the liver by the enzymes alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). The first one converts alcohol in acetaldehyde, which is a toxic substance for the body. Alternatively, the ALDH enzyme converts the acetaldehyde in acetate, decreasing the concentration of acetaldehyde and its toxic effects. These enzymes have several structures and are codified by different genes. The ADH4 gene is part of the alcohol dehydrogenase family. Studies have illustrated that individual genetic variants can influence the conversion rate of alcohol in acetaldehyde and acetaldehyde in acetate, changing the velocity of alcohol metabolization and, consequently, the amount of alcohol consumed, which is directly related to the augmented risk of alcohol abuse and dependence.