People are not born to become alcoholics or abstainers. Alcohol, after all, is a relative newcomer in the history of human evolution, even though it has been with us since before the ancient Egyptians.
What people are born with are a variety of genes and their protein products that alcohol can affect to produce a broad spectrum of responses, ranging from disinhibition, pleasure, euphoria and addiction, to physical revulsion.
The most common effect of alcohol is the first one that most people experience: Its ability to calm the brain, dilute worries, dissolve inhibitions and make people more sociable. increase sociability.
It does so by dramatically altering the main communication links between brain cells called NMDA and GABA receptors. Receptors are intake ports on the surface of neurons through which neurotransmitters enter to deliver messages to the cell’s genetic command center.
GABA receptors are the brain’s red light, telling neurons to keep quiet and not to speak until spoken to by other neurons. Otherwise neurons would all be speaking at once, creating a chaos that would make the brain unable to focus.
NMDA receptors, on the other hand, are the brain’s green light, urging brain cells to talk to each other when it is necessary to encode memories, generate thoughts and make decisions.
Alcohol reinforces GABA’s red light and subdues NMDA’s green light, thereby causing neurons to slow their communication with each other.
As increasing amounts of alcohol are consumed, GABA receptors become more hardened in their determination to prevent brain cells from communicating. NMDA receptors compound this effect by becoming increasingly helpless to allow neurons to hold a coherent dialogue.
The brain has a hard time communicating with nerves and muscles in the rest of the body. Standing turns to swaying, and staggering takes the place of walking.
With more drinking, brain cells can no longer communicate with each other, leading to blackouts, the inability to remember the night before.
In some people who are depressed, alcohol stimulates the production of the mood-lifting neurotransmitter serotonin, brightening their outlook, at least temporarily.
Scientists have found that mice drink more alcohol when they have been genetically engineered to lower the amount of serotonin entering their brain cells. They also become more aggressive.
People who are at the greatest risk of developing drinking problems or becoming alcoholic are those who don’t seem to get much joy out of life. They have lower than normal levels of dopamine to trigger their brain’s reward center.
Alcohol stimulates more dopamine production, giving them a feeling of pleasure that they seek to repeat over and over again. They don’t necessarily drink alcohol for its euphoric effect but to “feel normal.” The dark side is that heavy drinking may deplete the brain’s stores of dopamine and serotonin to the point at which depression sets in when drinking is stopped.
Outside of those who don’t drink for moral, religious or health reasons, many people find alcohol unappealing because it makes them flush, dizzy, headachy, drowsy or nauseated. Liver enzymes that are supposed to break down alcohol into harmless products fail to do the job. Alcohol then acts more like a poison in their body.
Scientists have found a gene mutation responsible for this negative effect, which may explain why Chinese, Japanese, Koreans and many Ashkenazi Jews avoid alcohol. But the mutant gene is no guarantee against alcoholism because a person who finds himself in a drinking crowd can learn to overcome the uncomfortable sensations.
Scientists now believe that the road to alcoholism requires genetic signposts that increase a person’s risk followed by a determined drive to drink.
In other words, genes only increase a person’s risk of alcoholism, but they do not preordain that fate. A person who has a genetic vulnerability still has to learn to drink and drink regularly.
It happens surreptitiously. A person doesn’t know he has a genetic predilection for alcohol, even though alcoholism may run in his family. He drinks to keep up with his peers, and before he realizes it he is dependent on alcohol. Typical are those youngsters at high risk who start drinking at age 12 or 13 and become alcoholic by 16.
“Young people initiate drinking not because they have a genetic need for it, but it’s just that the peer group allows drinking and you start drinking,” said Dr. Ting-Kai Li, a pioneer in the study of the genetics of alcoholism at Indiana University and the incoming director of the National Institute on Alcohol Abuse and Alcoholism.
“Starting to drink is very much influenced by the environment,” he said. “Once you start drinking what determines continuation and then maladaption to drinking becomes more and more influenced by genetics.”
Li and his colleagues were the first to breed rats that preferred alcohol to water. When they examined the animals’ reward centers, the researchers found that alcohol was pumping out the pleasure-neurotransmitter dopamine.
Another point is becoming clear: There are many gene variations that can predispose a person to alcohol abuse or alcoholism, and a lot of people have different mixes of them.
When one member of a pair of identical twins becomes alcoholic, his twin has a 50 to 60 percent risk of also becoming alcoholic. Identical twins have the exact same genes. That the risk is not 100 percent underscores the influence of the environment in alcoholism.
A person whose father is alcoholic has a 20 to 30 percent risk of also becoming alcoholic. If both parents are alcoholic and if grandparents and siblings are alcoholic, the risk increases.
Yet a person with all the worst genes for alcoholism will not become alcoholic if he doesn’t drink.
But a lot of people succumb. More than half of all U.S. adults report a family history of alcoholism or problem drinking. One out of 13 Americans is considered alcoholic, and nearly 1 out of 5 will experience alcohol abuse or dependence.
Over time alcohol changes the pattern of brain receptors. When alcohol affects GABA, NMDA and other receptors, it acts like a general-purpose neurotransmitter.
Alcohol overstimulates GABA receptors. To compensate, the brain makes fewer GABA receptors in order to adapt to the overabundance of alcohol.
NMDA receptors act just the opposite. They are blocked by alcohol so the brain makes more of them in an attempt to enable neurons to carry on with their work.
This overproduction and underproduction of receptors sows the seeds for tolerance, craving, dependence and addiction. More alcohol is needed to overcome the brain’s effort to reconfigure its balance of receptors. When drinking is stopped, brain cells send out desperate signals for either alcohol or their natural neurotransmitters, neither of which are available.
Neuronal communications turn to static. Nerves are jangled, the dark cloud of depression spreads, stress hormones churn, bad connections create deliriums, sweat pours–withdrawal is painful for the most-addicted individuals.
Although the American Medical Association declared alcoholism a “disease” in 1956, the topic has been hotly debated. Some contend it is a matter of willpower and moral backbone, while others cite the genetic propensity.
Alcoholism is beginning to be seen in the same category of such disorders as heart disease, cancer and other chronic ailments. People may have genes that make them vulnerable to these diseases, but they may never develop them if they avoid such environmental triggers as smoking, high fat diets and indolence.
“If you find a vulnerability or a variant of a gene that might predispose someone to alcoholism or some other disease and that places the person at risk for adverse consequences, then from that perspective alcoholism is a disease,” Li said.
Defining alcoholism as a disease that has its roots in both genetic and environmental influences opens the door to new treatments, Li said.
Prevention programs need to be focused on families and individuals who have a high genetic risk for alcohol abuse, he said. Studies show that intervention programs can foil genetic vulnerabilities. And although abstinence is necessary for hard-core alcoholics, less severe drinking problems can often be handled by curbing excessive drinking, he added.
Researchers are also trying to develop drugs to neutralize alcohol’s effects on the brain. Naltrexone, originally developed to combat heroin addiction, is used to treat alcoholics. It works by blunting alcohol’s ability to stimulate the release of dopamine in the brain’s reward center.
Antidepressants such as Prozac increase serotonin levels and are useful in helping some people reduce their dependence on alcohol.
“The message is that alcoholism is a heterogeneous genetic disease and it’s treatable,” Li said. “The success of alcoholism treatment is no worse than the treatment of heart disease, hypertension or asthma.”
