Alcohol & Genes 

Alcohol dependence is a major global problem, associated with lower quality of physical and mental health, higher mortality and an enormous familial and social cost. Prevention strategies and treatment of this condition are therefore crucial. Success of psychosocial programs and pharmacological treatments has been frequently reported, but a better understanding of the etiology of this chronic disease is needed. For this purpose, the identification of associated factors in different populations is of great significance.

It has been clearly demonstrated by twin and adoption studies and supported by animal models that both genetic and environmental components play a substantial role in alcohol dependence. Heritability estimates range from 40 to 60%, depending on the specific analyzed sample.

Most research points to an association between alcohol dependence and genes related with alcohol metabolism, with neurotransmission of dopamine, GABA, serotonin, glutamate, endogenous opioids, and cannabinoids, signal transduction within the mesolimbic dopamine reward system, and stress response system, among others.

During pregnancy, there are several non-genetic factors that may have an important impact on vulnerability to alcohol dependence. Given that the Central Nervous System is developing throughout the entire pregnancy and that alcohol consumed by the mother can reach the fetus through the placental barrier, the brain of a baby is always vulnerable to harm caused by alcohol exposure. Children born to alcoholic mothers may inherit genetic susceptibility variants but at the same time they may be exposed to early effects of ethanol. Heavy alcohol exposure during pregnancy has been associated with mental retardation, epilepsy, attention deficit/ hyperactivity disorder, learning disabilities, and later on with substance abuse, anxiety, personality, affective and psychotic disorders, as well as with engagement in antisocial behaviors and school or work problems.

Furthermore, it has been shown that animals exposed to prenatal stress exhibit persisting modifications related to dopamine and glutamate transmission in limbic structures associated with dependence to alcohol and other substances. These alterations may later contribute to increase motivation to drink, to use large amounts of drugs of abuse or to relapse after periods of drug withdrawal. It was shown that after exposure to prenatal stress, male mice consumed more ethanol during alcohol reinforcement in adulthood.

Adolescence is a critical period for initiation of alcohol intake, experimentation, and establishment of regular drinking patterns. Substance use at this age is considered a risk factor for the development of later alcohol and other drug-related problems, as well as for externalizing disorders such as antisocial personality disorder. Alcohol use initiation is affected by environmental factors such as ethanol availability, parental attitudes, and peer pressure. It has been reported that heavy drinking during adolescence can have a negative impact on brain development. Moreover, dopaminergic and GABA systems undergo important changes during adolescence, and they can be affected by alcohol intake. Dopamine is implicated in the rewarding effects of ethanol, and GABA in its sedating effects and development of tolerance.

The way an adult copes with environmental challenges is notably influenced by early life experiences and by the familial environment he or she had as an infant, which affects neurodevelopmental behavior.

While environmental factors tend to have a crucial role in drinking habits in adolescence, adulthood may be characterized by a weaker effect of environment and a higher effect of genetic components.

It is probable that a complex set of gene–environment interactions determine the risk to alcohol dependence. Environmental factors that may affect this vulnerability appear at different stages from pregnancy to adulthood. 

References: Salud Mental; mar2011,Vol. 34 Issue 2, p157-166, 10p, 1 Diagram, 1 Chart-