Wrong genes in the right hands
Previously published by: http://www.smh.com.au
July 24, 2004

New genetic research has underlined the importance of nurturing children, writes Deborah Smith.
Mark Twain said of the weather that although a great deal had been said about it, very little had ever been done about it. How nature and nurture contribute to the complex ways humans behave has tended to fall into the same category, say scientists.

When a search for genes linked to violence was first proposed more than 12 years ago, there was an uproar, with opponents arguing it could lead to genetic discrimination and detract from the social causes of crime. Debate has raged since.

"Everyone was talking about behavioural genetics for donkeys years, but no one was doing anything about it," says a New Zealand researcher, Professor Richie Poulton.
Finally, however, things have changed. Scientists have recently begun to uncover the interactions between specific genes and life events that can lead to problems such as rage and antisocial behaviour, or to depression and suicide. And Poulton, of the University of Otago, has been leading the charge with British and New Zealand colleagues.

Two years ago this team discovered a genetic variation in men in New Zealand which made them more likely to be violent. But it had an effect only if the men had also been abused as children.

This month researchers in the United States confirmed this gene-environment interaction in a study of more than 500 boys. The same effect is seen in monkeys genetically predisposed to violence and deprived of their mothers' care from birth, researchers at a conference on genes and violence in London said this week.

Poulton's team has more recently identified a genetic variation that increases the risk of people becoming severely depressed, but again, it only comes into play if they have suffered stressful events - a find that was rated among the top 10 discoveries last year by the journal Science.

Poulton says the irony of the genetic revolution, and the newfound ability to identify the nature side of the equation, is that it has revealed how critical the nurture side is.

"The environment is the switch which turns the gene effect on or off," he says. "You're partly a product of your genetic endowment and partly of what happens to you in life."

Rather than put hope in high-tech solutions like designing new drugs or tinkering with genes to prevent antisocial behaviour, the answer is to "minimise the environmental risk".

To prevent violence, society must prevent maltreatment of children. "Parents who are struggling need to be supported in many ways," he says.

New Zealand has become a leader in the field partly because of an extraordinary 26-year health study of more than 1000 people that was begun in Dunedin in 1972 when very little was known about genes.

Every baby born in the city's only maternity hospital in a 12-month period was enrolled and to make sure people stayed in the study researchers flew them back for tests from wherever they were in the world.

Participants underwent extensive physical and psychological assessments every two years until the age of 15, and then again at 18, 21 and 26.

For the violence research, Poulton and his colleagues tested 442 men for variations in a gene called MAOA, which controls the level of an enzyme that breaks down three important brain chemicals.

They found that 85 per cent of men who had a low-activity version of the MAOA gene and who had also been severely maltreated as boys had gone on to develop antisocial behaviour such as violent criminal activity as adults. Men who had been maltreated as children but had a high-activity version of the gene were much less likely to become violent, a finding that helps explain why not all abused people end up abusing others.

To gain credence, replication was important. This month a US team led by Dr Debra Foley at Virginia Commonwealth University reported in the Archives of General Psychiatry that it had done this. It studied 514 white male twins aged eight to 17 years, and their parents.

Children with the low-activity version of the MAOA gene did not have an increased risk of conduct disorders, the Americans found, unless they had also been severely maltreated.

Foley says the search for genes linked to behaviour and mental health has had a disappointing history, and her study suggests this is because life experiences have been ignored. "In projects designed to identify genetic risk factors for psychiatric disorders ... it will be important to collect detailed environmental histories as well as DNA."
The ability of good parenting to counteract the effects of genes that predispose to violence - at least in monkeys - was outlined this week by Dr Stephen Suomi, of the National Institute of Child Health and Human Development in Bethesda, Maryland.

His team tested rhesus monkeys for a gene called 5HTT, which influences how the brain deals with the "feel good" neurotransmitter serotonin.

Monkeys with the "bad" genetic variation linked to aggression were normal if they had been raised by their mother. But they were very violent if they had been separated from her at birth.

Monkeys with a "good" version of the gene were placid, irrespective of their upbringing. "There is a buffering effect of good mothers," Suomi says.

Poulton's team studied the 5HTT gene too, in 847 people in the Dunedin study. Stressful life events between age 21 and 26, such as romantic break-ups, bereavements, serious illnesses and job crises, were counted. And depressive episode and suicidal tendencies in the previous 12 months were assessed at the age 26 check-up.
The risk of a severe depressive episode was twice as great in people with two copies of the "bad" version of the gene who had had four or more stressful events, compared with people with two copies of the "good" version of the gene whose lives had been similarly tumultuous.

Poulton says it may be possible in future to identify people with this genetic predisposition to depression and help them minimise stress.

But another worthwhile approach would be to try to determine the brain chemistry that protects part of the population from succumbing to depression and allows them to bounce back easily from life's vicissitudes.