[abstract below]
The likelihood that an abused child will become antisocial or violent as an adult hinges partly on a gene that influences brain chemistry, scientists report today, suggesting that some children carry a built-in shield against trauma and stress.
In a provocative study that tracked 442 New Zealand boys from birth into their mid-20s, an international team of researchers found evidence of a potent interaction between child abuse and a gene known as MAO-A. The study appears today in the journal Science.
The results highlight the importance of tying gene function to factors in the environment, particularly during early childhood, that can powerfully shape just how and when a gene kicks in. It's often the interaction, more than the gene itself, that really counts, even though that can be an elusive area to conduct research.
"This is one of the first demonstrations of an interaction between a gene and an environmental pathogen," said Terrie Moffitt, a psychologist at the University of Wisconsin at Madison and a co-author of the study. "Looking for a direct one-to-one interaction between a gene and a disorder is usually the wrong way to go."
The MAO-A gene produces a brain enzyme called monoamine oxidase A, long known to soak up excess quantities of the neurotransmitters dopamine, serotonin and norepinephrine, all key chemical messengers in the brain.
The same gene can come in a high-activity or low-activity form. Previous studies in humans as well as animals have documented a clear link between violent tendencies and the low-activity form of the gene.
In the new study, 85 percent of the severely maltreated boys who also had the low-activity form exhibited some kind of antisocial behavior later in life.
The combination of maltreatment and a low-activity MAO-A gene was found in only 12 percent of all the boys in the study, but was a factor in 44 percent of their violent crimes.
All told, the odds of an abused child with the low-activity MAO-A gene developing antisocial problems worked out to be roughly equivalent to the risk of someone with high cholesterol developing cardiovascular disease.
However, the researchers emphasized that the MAO-A factor was not strong enough to predict which abused children might develop antisocial problems. Instead, the presence of one gene form or another merely shifts the odds -- leaving plenty of room for variation among individuals.
The data was drawn from a large and continuing health study begun in 1972 by the New Zealand government, designed initially to examine the long-term effects of birth complications.
Nearly 1,100 children -- all those born in a certain hospital during a one- year period -- were evaluated repeatedly for health and behavior patterns through age 26. Another study is planned based on the participants at age 32.
In today's study, researchers focused mainly on the males, who proved easier to study in part because they exhibited more antisocial behavior than the females. Also, boys inherit only one copy of the MAO-A gene, while girls have two copies.
Scientists speculated that one reason females tend to exhibit less antisocial behavior could be that females have twice the odds of inheriting at least one high-activity form of the MAO-A gene.
Independent experts called the study one of the most ambitious attempts yet to unmask the complex genetics of human behavior.
"People have to get used to the idea that there are probably genetic influences on many kinds of behavior," said Dr. Hans Steiner, a psychiatry professor at Stanford University School of Medicine. "That's not a bad thing. It's not the whole story, but it's certainly plausible that genes are involved.
The question is not do they or don't they have an influence, but how much."
The study does not seem likely to lead to any new strategy for treating those with a history of child abuse, whatever their genetic makeup. There are no drugs known to boost the brain's stores of high-activity MAO-A -- and none are likely to be developed anytime soon given such a minuscule market.
Abstract
Avshalom Caspi,12 Joseph McClay,1 Terrie E. Moffitt,12* Jonathan Mill,1 Judy Martin,3 Ian W. Craig,1 Alan Taylor,1 Richie Poulton3
We studied a large sample of male children from birth to adulthood to determine why some children who are maltreated grow up to develop antisocial behavior, whereas others do not. A functional polymorphism in the gene encoding the neurotransmitter-metabolizing enzyme monoamine oxidase A (MAOA) was found to moderate the effect of maltreatment. Maltreated children with a genotype conferring high levels of MAOA expression were less likely to develop antisocial problems. These findings may partly explain why not all victims of maltreatment grow up to victimize others, and they provide epidemiological evidence that genotypes can moderate children's sensitivity to environmental insults.
1 Medical Research Council Social, Genetic, and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College, London SE5 8AF, UK.
2 Department of Psychology, University of Wisconsin, Madison, WI 53706, USA.
3 Dunedin School of Medicine, Box 913, University of Otago, New Zealand.
* To whom correspondence should be addressed. E-mail: t.moffitt@iop.kcl.ac.uk
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