Addiction is not simply genetics. IRISH TIMES Science Today

8 Mar 2012

It would be wonderful to attribute our penchant for addictive damaging activities, such as overeating, smoking cigarettes or binge drinking, wholly on our genetic make up. Then we could really blame our parents for everything. All current research suggests, however, that a variety of factors influence an individual’s propensity for compulsive behaviour.

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The recent Government campaign highlighting obesity has made more people aware of this increasing problem. The campaign aims to convince individuals to take responsibility for their own actions. But while no one is immune to addictive tendencies, some are more prone than others.

Research from the US suggests a preference for fatty foods may have a genetic basis. A study discovered that people with certain forms of the CD36 gene may like high-fat foods more than those with other forms of this gene.

“We have plenty of evidence to suggest that genetics and disease are linked but we’ve been trying to figure out if there’s any relationship between genetic variation and behaviour for a long time,” explains Dr James McInerney of the molecular evolution and bioinformatics unit at NUI Maynooth. “That’s what makes this research so significant.”

The study carried out by scientists from a number of US universities involved 317 African Americans. A DNA sample was taken from each volunteer. They were given salads, with dressings that had varying amounts of oil content – 5 per cent, 35 per cent and 55 per cent oil. It was hidden to them how much oil was in the salad.

“They were then asked to self report as to how oily the salad was, how much fat content they thought was in the salad, and how creamy it was,” says McInerney. “People with the particular CD36 genotype had a much higher acceptance of added fat and oils and didn’t find the 55 per cent dressing to be too oily.”

In other words, the CD36 gene has an effect on our perception of fat and gives carriers a higher tolerance and preference for fatty foods. So there is an argument for a genetic predisposition to obesity.

We know eating too much fatty food is bad for us and yet we still do it. Prof Paul Kenny is an Irish scientist based in the Scripps Research Institute in Florida. Much of the work carried out in his lab focuses on the links between addiction and genetics and Kenny has been involved in some fascinating recent discoveries.

“Thirty per cent of the US population are obese,” says Kenny. “Everyone here knows that if you eat certain foods, they will be harmful and yet they still do it.”

So it seems conscious awareness is not sufficient in some individuals.

“We carried out some simple tests where we gave rats extended access to junk food – cheesecake, bacon, cupcakes, etc – to see if they would develop compulsive behaviour,” he said.

Some of the animals had been modified, losing their ability to react to an important neurotransmitter, Dopamine D2. The loss was meant to mimic genetic variation found in humans addicted to drugs.

“These rats eventually had no control over their eating habits and became obese. We gave them the option of eating healthier food that they were brought up on but they always went for the junk,” Kenny said.

“We then took away the high-fat food and left standard food but they wouldn’t eat it. Instead, they starved themselves. The study demonstrates that over-consumption of high-fat food triggers addiction-like neuro adaptive responses in our brain-reward circuitry and drives the development of compulsive eating.”

Like everyone researching the area of genetics and addiction, Kenny is quick to point out that genetics plays but one part. “The compulsive behaviour in the animals came about after extended access to fatty foods,” he says.

“If we knocked out the D2 receptor and gave them bad food once, nothing would happen. But if we do it for a long time, then it has an effect. So genetics and environment are working together.”

While the idea that trying a drug once will lead to automatic addiction is a myth people tell their children to discourage experimentation (it is estimated that only 23 per cent of heroin users become dependent on the drug), some addictive substances only need to be consumed once for a permanent susceptibility to addiction to occur.

“We are interested in cocaine dependence as our model,” explains Prof John F Cryan of the Alimentary Pharmabiotic Centre in Cork. “Cocaine is both psychologically and physically addictive and causes long-term changes in the dopamine-reward pathway of the brain, some of which don’t become reversed following withdrawal. It means there’s a signature that remains in the brain that makes even the one-time user susceptible to relapse because of permanent molecular changes.”

This is not the case for all drugs. Others require longer exposure for dependence to develop. But preventing teenagers and young adults any access to drugs is always a good idea.

“Addiction is a disease of the young with alcohol being the only exception,” explains Prof William O’Connor of the University of Limerick.

“There’s a reason why you don’t find 60-year-old cocaine or heroin addicts. The different sections of the brain of a young person mature at different rates. Although they have fully formed reward pathways by 12-15 years old, they don’t have a fully formed frontal lobe, which is the decision-making centre in the brain. This doesn’t mature till your late 20s.”

Young people know what they like but they’re not good at judging the consequences. “This might seem like a major evolutionary flaw of human behaviour but it has its advantages,” says O’Connor. “Young people are prepared to take more risks, become entrepreneurs . . . We use this trait in young people by putting them on football teams, or into the army. There’s a place for risk-taking in our society.”

As biologically deterministic as that may sound, free will always prevails and the same is the case with addiction. “There was a study done that showed children of alcoholics are four times more likely to become addicted to drink, even if they’re brought up away from their natural parents,” says O’Connor.

“But the key point here is: we are not just our genetics, we all have aptitudes, traits, susceptibilities. Addiction is a three-legged stool – with biological, psychological and social elements. Genetics is just one part of it.”

The habenula: Our genetic guardian angel  

IN OLD MOVIES, characters with a dilemma are often depicted as having an angel on one shoulder telling them what they should do, and a devil on the other telling them what they shouldn’t. It seems the human brain has its own built-in anti-hero mechanism that tries to steer us on to the right path.

If free will wasn’t enough, it turns out our brains are trying to fight the human propensity for addiction too. Genetic predispositions may make some of us more inclined to make bad decisions but other physiological traits still try to protect us from ourselves.

Research from the Scripps Institute in Florida suggests that part of the brain known as the habenula triggers an inhibitory motivational signal that acts to limit intake in our brains after prolonged exposure to negative activities, such as smoking, heroin use or over-eating.

“When people develop a dependency to something, they don’t do it to feel bad,” says Prof Paul Kenny of the Scripps Institute. “They take a drug to feel good, or at least that’s how we typically think of the logic behind addictive behaviour.

“But what we have found is that when you smoke, for example, there’s only a small range of doses that feel pleasant. If you take a little more it becomes aversive and you don’t like it. This is because the habenula is being activated.

“When something good happens to you, your brain-reward centres turn on. The reason why they turn off when something bad happens is because of the habenula. It is like the evil twin of the brain reward centre or good twin in the context of addiction, depending on how you look at it.

“But it is essentially an anti-pleasure centre in terms of how it makes you feel. And it only works when you’re doing things that are bad for you.” – John Holden 

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