Saturday, March 03, 2007

Addict brain 'designed for drugs'

Physical differences in the brain may increase the chances of a person choosing to take drugs, say Cambridge University scientists.

A study of rats showed variations in brain structure pre-dated their first exposure to narcotics, and made them more likely to opt for cocaine.

Writing in Science, the team say genes may affect these differences in humans.

Treatments to reduce their effect may be found - but a test of vulnerability to drugs is unlikely, they add.

Up to 500,000 people are currently addicted to Class A drugs such as cocaine, heroin and amphetamines, according to government figures.

One of the most important questions in the science of addiction surrounds the origin of differences noticed in the brains of human drug users.

While these differences are thought to be important in the way humans respond to drugs, it is difficult to prove whether they are a part of the natural brain chemistry of that individual, or have developed as a result of taking the drugs themselves.

To unravel this problem, the Cambridge researchers scanned the brains of rats, and found similar differences in 'neurotransmitter receptors' in certain parts of the brain.

Some of the animals had far fewer 'dopamine receptors' - the brain structures onto which drugs such as cocaine and heroin latch to produce their effect.

The scientists used a game in which the rats had to wait to press a button and receive a reward, coupled with detailed brain scans, to see if those with the fewest dopamine receptors were impulsive, a type of behaviour often linked with drug use in humans.

This was the case - even in rats which had no contact with drugs.

When the 'impulsive' rats were introduced to the drugs, and given the opportunity to take them, they were much more likely to do so than the rats with more dopamine receptors.

Dr Jeff Dalley, who led the study funded by the Medical Research Council and the Wellcome Trust, said that this showed clearly that the brain differences, and the impulsivity linked to them, pre-dated any exposure to drugs, with the possibility that the situation in human drug users could be the same.

"What we are talking about here is a possible physical trait producing vulnerability to drug use.

"The next step is identifying the gene or genes that cause this diminished supply of brain receptors.

"This may provide important new leads in the search for improved therapies for attention deficit/hyperactivity disorder (ADHD) and compulsive brain disorders such as drug addiction and pathological gambling."

But he said that the reasons for humans becoming addicted to any drug were more complex than simply their genetic make-up, and that a test for any gene uncovered by further research would not necessarily work.

"There are lots of reasons unconnected to genes why people use drugs, and I can't see that any test would be useful."

Lesley King-Lewis, Chief Executive of Action on Addiction, said: "It is well known that some personality traits are associated with a vulnerability to cocaine and other addiction problems.

"This study is extremely interesting because it has identified a biological basis in rats for some of the behaviours that we know are associated and shows how they can lead to drug addiction."

Dr Gerome Breen, from the Institute of Psychiatry in London, said that the differences found in the rats were very likely to have their equivalent in the human brain.

"This is a very exciting study which has successfully identified the biological basis of some of the behaviours that we know are associated with higher risk of cocaine and other addictions in humans.

"It also pinpoints a potential cause of relapse in abstinent drug users - what makes them start taking a drug again despite all the problems they know it will cause them.

"This means that we can start to investigate treatments that, at least partially, correct this deficit in the hope that these will prove successful in preventing relapse."

Shyness and Genes

A related study on resilience and genes posted on on this weblog May 7th (see also the Dec. 2nd post on antisocial behavior) turns this relationship on its head. It too notes that a genetic predisposition to certain behavior--in this earlier report, the ability to tough it out in the face of adverse circumstances--is triggered or not by environmental influences.
In recent years, biological science has proposed a new paradigm. The latest research shows that resilience can best be understood as an interplay between particular genes and environment — GxE, in the lingo of the field. Researchers are discovering that a particular variation of a gene can help promote resilience in the people who have it, acting as a buffer against the ruinous effects of adversity. In the absence of an adverse environment, however, the gene doesn't express itself in this way. It drops out of the psychological picture. "We now have well-replicated findings showing that genes play a major role in influencing people's responses to adverse environments," says Sir Michael Rutter, a leading British psychiatrist ...

Genes and stressed-out parents lead to shy kids

New research from the Child Development Laboratory at the University of Maryland shows that shyness in kids could relate to the manner in which a stress-related gene in children interacts with being raised by stressed-out parents.

In a study published in the February issue of Current Directions in Psychological Science, Nathan Fox, professor and director of the Child Development Laboratory, and his team found that kids who are consistently shy while growing up are particularly likely to be raised by stressed-out parents, and to possess a genetic variant associated with stress sensitivity.

This suggests that shyness relates to interactions between genes and the environment, as opposed to either genes or the environment acting alone. "Moms who report being stressed are likely to act differently toward their child than moms who report little stress," said Fox. "A mom under stress transfers that stress to the child. However, each child reacts to that stress somewhat differently. Our study found that genes play a role in this variability, such that those children who have a stress-sensitive variant of a serotonin-related gene are particularly likely to appear shy while growing up when they also are raised by mothers with high levels of stress.

"We don't understand how the environment directly affects the gene, but we know that the gene shows particularly strong relationships to behavior in certain environments."

Like all genes, the particular serotonin-related gene examined in this study has 2 alleles, which can be long or short. The protein produced by the short form of the gene is known to predispose towards some forms of stress sensitivity.

Fox's research found that among children exposed to a mother's stress, it was only those who also inherited the short forms of the gene who showed consistently shy behavior.

"If you have two short alleles of this serotonin gene, but your mom is not stressed, you will be no more shy than your peers as a school age child," says Fox. "But we found that when stress enters the picture, the gene starts to show a strong relationship to the child's behavior," says Fox. "If you are raised in a stressful environment, and you inherit the short form of the gene, there is a higher likelihood that you will be fearful, anxious or depressed."

Fox's group studies how genes and the family environment work together to shape the development of social competence in infants and young children. "We are particularly interested in very shy children. What keeps them shy and what may change them from being shy to not being shy anymore?

"We identify these children early in the first years of life, but it's not enough to identify a child with a certain disposition or gene. We want to understand how the environment works together with genes, what are the mechanisms that shape behavior."

Source: Association of Psychological Science