The causes of addiction are complicated. They include childhood experiences, traumatic experiences, mental health issues, and learned behavior. One of the biggest factors in addiction appears to be genetics, accounting for about half of addiction risk. A number of genes have already been associated with a higher risk of addiction, and now there’s new research that gives us insight into the genetic causes of addiction.
A study led by researchers from Linköping University in Sweden has identified a gene that appears to be associated with alcohol addiction. The researchers trained rats to press a lever to receive alcohol, then they introduced sugar water as an alternative to the alcohol. When offered this new alternative, most of the rats preferred the sugar water, but about 15 percent of the rats still prefered the alcohol. This is roughly comparable to the percentage of humans who develop alcohol use disorders. This preference persisted even when the rats were given a mild shock whenever they pressed the lever to dispense the alcohol. This behavior is similar to addictive behavior in humans, who are often aware their substance use is hurting them, but persist anyway.
The team then examined hundreds of different gene expressions in five different regions of the rats’ brains, looking for notable differences. The most striking difference was in the genetic blueprint for a protein called GAT-3. GAT-3 is a transport protein responsible for clearing GABA away from neurons. The researchers found that GAT-3 levels were extremely low in the amygdalas of the rats that preferred to drink alcohol in spite of the shocks.
To test whether they had really found the right gene, the team then knocked out the GAT-3 gene in the mice that had previously preferred sugar water to alcohol and repeated the experiment. The mice that had previously preferred the sugar water now preferred alcohol.
This result makes sense in terms of what we already know about alcohol addiction. One of the main ways alcohol affects the brain is by enhancing the effect of GABA. GABA is an inhibitory neurotransmitter, which means it damps down the activity of neurons. This is one of the two main mechanisms by which alcohol makes you feel relaxed. The other is that alcohol inhibits the effect of the excitatory neurotransmitter glutamate.
The amygdala is a structure–or actually two structures, left and right–near the center of the brain. It plays a role in many different functions related to emotion and memory, but one of its most important functions is the fear response. The amygdala is important for recognizing threats and initiating the fight or flight response. The amygdala is hyperactive in people with anxiety disorders, bipolar disorder, and post-traumatic stress disorder, or PTSD.
This new research shows one possible reason a certain percentage of people find alcohol so appealing, while others can take it or leave it. If GABA accumulates around the amygdala because there isn’t enough GAT-3 to clear it away quickly, it could mean that in those people–and rats–that the anxiety generated by the amygdala gets the volume turned way down. That would be especially appealing for people with social anxiety disorder, bipolar disorder, and PTSD. And, in fact, we see a high rate of alcohol misuse among people with those conditions.
Of course, this is largely speculation, unless the same gene is found to serve the same purpose in humans. To test this, the Swedish team partnered with researchers at the University of Texas in Austin. The researchers in Texas tested GAT-3 levels in deceased humans and found that the brain tissues of people with documented alcohol addictions has lower levels of GAT-3. It’s unusual to find such strong evidence validating animal models in humans. The Texas team’s findings strongly indicate that low levels of GAT-3 contribute to alcohol addiction in humans.
This research may help point the way to new treatments for alcohol addiction in humans. The drug baclofen is currently being studied for use in treating alcohol withdrawal. Baclofen activates GABA receptors, causing a similar inhibitory effect. If excess accumulation of GABA in the amygdala does play a part in alcohol addiction, it could be that the excess GABA forces a dramatic downregulation of GABA, leading to the irritability, shaking, and seizures common in alcohol withdrawal. Baclofen or other drugs that affect GABA levels may help ease the transition to sobriety.
It’s worth noting that despite the strong evidence that GAT-3 plays a major role in alcohol addiction, we can’t simply say that one particular gene causes alcohol addiction. There may be environmental factors that influence how the gene is expressed. That is, much of our DNA can be turned on or off, so there may be other factors influencing how much GABA is present in the amygdala.
This study also doesn’t invalidate psychotherapeutic methods such as cognitive behavioral therapy, or CBT. It simply shows that some people are genetically predisposed to get more relief from anxiety when they drink. Similar results can be achieved with CBT and other research-backed forms of therapy. That’s because CBT helps you learn different ways to process threatening situations, which has the same result of calming the activity of the amygdala. By way of analogy, there are many ways to turn off your car. Most people prefer to use the ignition, but you could conceivably drive it into a pond and flood the engine. Using alcohol to relieve anxiety is much closer to the pond method, while therapy is like turning the key.
If you or someone you love is struggling with alcohol addiction or mental illness, The Dawn Medical Rehab and Wellness center can help. We are one of Thailand’s most respected addiction treatment and wellness centers. We use cutting-edge treatment modalities to provide personalized care to treat addiction, depression, anxiety, bipolar disorder, personality disorders, PTSD, and executive burnout. See our contact page to reach us by phone or email.