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A Sobering Story: Experts say genetics play key role in addictions

by on April 20, 2014 1:59 AM

Addiction isn’t a problem of mind over matter. Really, it’s a matter of the mind.

“(Addiction) looks like bad behavior, but in essence it’s a biological problem, a biological transformation, if you will, as a result of the drug use,” said Dr. Kenneth Thompson, medical director of the Caron Treatment Centers.

According to Thompson and other addiction specialists, the problem arises from a complicated mix of genetics, biology, psychology, peer influences, environment and lifestyle, and it perpetuates itself by impairing the parts of the brain that are critical to judgment, decision-making and behavior control.

But of those factors, genetics appear to play an especially significant role in the formation of addiction. In fact, genetics account for between 50 and 75 percent of the risk for it, according to a 2012 report by the National Center on Addiction and Substance Abuse at Columbia University (CASA).

“Whereas biological, psychological and environmental factors — such as impairments in the brain’s reward circuitry, compensation for trauma and mental health problems, easy access to addictive substances, substance use in the family or media and peer influences — play a large role in whether an individual starts to smoke, drink or use other drugs, genetic factors are more influential in determining who progresses to risky use or addiction,” it stated.

To be sure, there is no one single addiction gene, and how any given gene expresses itself depends on factors such as the environment, as is the case with someone who has a genetic predisposition to, say, cancer or diabetes.

Overall risk of developing a disease, including addiction, arises in part from variations in many different genes.

“Addiction is variable. It takes the right sort of genes in the right combination with the right exposure to the right drug at the right time,” said Thompson. “All of those factors have to be present in a way.”

Some, he said, may inherit a set of genes that may be “on” from the beginning. And for those people, their “like” of the drug is immediate.

“Love at first taste,” he said. “This often results in a rapid escalation of use, which results in addiction. In others the progression is much slower.”

Anecdotally, some report having become addicted to a substance from the initial use, but Carlton Erickson, a pharmacology professor at The University of Texas at Austin and director of its Addiction Science Research and Education Center, said that science has yet to show that can occur.

The case largely is that people develop addiction through persistent use of a substance, which leads to changes in the way brain functions.

“One of the things that we know is that there are certain genes that get turned on as exposure to the drug continues. And that gene plays a role in … some of that loss of control,” said Thompson.

These impacts to the brain are both a cause and consequence of addiction. And they are not conjecture — they have been observed, and the disruptions can be clearly and precisely mapped in the brain, said Rube Baler, a health science administrator with the National Institute on Drug Abuse.

“With more sophisticated machines, we have ways of entering the brain and seeing how the brain behaves in health and in disease, addiction included,” he said.

“We can very clearly pinpoint disruptions in the way the different parts of the brain communicate with each other, how the neurotransmitters are released in response to a stimuli and triggers from the environment or internal triggers,” he said.

Substance abuse impacts the part of the brain known as the limbic system, which drives motivation and emotion and houses the brain’s reward circuit. The circuit is important to human survival because it helps drive us to do things necessary for survival, such as to eat and have sex.

The circuit is activated when a person carries out one of those acts, providing a pleasurable feeling, a “reward.” The reward helps spur repetition of the action.

“Our brains are wired to ensure that we will repeat life-sustaining activities by associating those activities with pleasure or reward. Whenever (the) reward circuit is activated, the brain notes that something important is happening that needs to be remembered, and teaches us to do it again and again, without thinking about it,” according to NIDA.

Most drugs play on the limbic system in some way by flooding it with dopamine, a neurotransmitter. While an act that is naturally rewarding will cause dopamine levels to increase, drug use floods the system with dopamine, sometimes two to 10 times the amount released through a naturally rewarding act.

That puts the limbic system into overdrive, and the resulting effect easily overpowers the good feelings that arise from natural acts. And because the effect is so great, it strongly motivates people to use again.

In time and with enough use, the brain adapts to the constant flood by dialing back dopamine levels.

“Just as we turn down the volume on a radio that is too loud, the brain adjusts to the overwhelming surges in dopamine and other neurotransmitters by producing less dopamine or by reducing the number of receptors that can receive signals,” NIDA said.

In other words, the abuser eventually comes to feel, flat, lifeless and depressed. And when that happens, a person may have to use simply to feel normal. To reproduce the high, they wind up having to use an ever-increasing amount.

Dopamine isn’t the only neurotransmitter that’s involved in drug use. There are others, and specialists said they’ve found that certain drugs will work on certain neurotransmitters, producing different effects.

Erickson said cocaine and amphetamine are most associated with dopamine. LSD works on another, serotonin. And endorphins are most associated with opioids, such as heroin. And the neurotransmitter glutamate is associated with alcohol.

But no matter the neurotransmitter, they generally all tend to affect the limbic system.

Thompson said another key area of the brain affected by addiction is the prefrontal cortex, which is responsible for higher level decision-making, self-control and modulating the brain’s reward system. Abuse “hijacks” that part of the brain, he said.

And as result, the limbic system runs without a governor, compelling people to continue using. Even though fully cognizant that it’s illegal, dangerous and causing life problems.

“The pathways of feedback or control are damaged, such that a person no longer can predictably control their drug use,” he said. “Because of the disregulation of the brain, and the fact that the prefrontal cortex is impaired, the person uses again,” Thompson said.

Therefore, specialists say, those who are addicted can’t say no, even if they want to.

READ MORE: Read the rest of this week's pieces of "A Sobering Story: The Disease of Addiction here, as well as last week's articles.

Do you or a loved one need help with addiction? Local resources are available here.



Sam Kusic is a staff writer for The Indiana Gazette.
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