Gene linked to how kids respond to abuse

New research identifies a genetic variation that might protect abused children from developing antisocial behavior.

Childhood abuse is a universal risk factor for antisocial behavior, says Terrie Moffitt, a UW–Madison psychologist who contributed to the study. Children who have suffered physical or sexual abuse are twice as likely to develop conduct disorders as adults, yet, as Moffitt explains, which of them will have behavior problems later on greatly varies.

The new findings, scheduled for publication in the Aug. 2 issue of the journal Science, suggest that a genetic variation associated with low levels of a certain brain enzyme may make some abused children nine times more likely to exhibit antisocial behavior.

As many psychologists search for environmental factors linking childhood maltreatment and adult antisocial behavior, the group from Wisconsin has looked to a gene that regulates levels of monoamine oxidase A (MAO A) – an enzyme that cleans up excess neurotransmitters, chemicals in the brain that transmit nerve signals. Previous studies of MAO A activity in both mice and humans have shown that low levels of this enzyme increase aggressive behavior.

“There are known genes that protect against malaria and other parasites,” says Moffitt. “We wanted to know if a particular MAO A genotype could protect maltreated children against antisocial behavior.”

The research group, led by UW–Madison psychology professor Avshalom Caspistudied 442 males living in New Zealand for 26 years beginning at their birth. The subjects were part of the longitudinal Dunedin Multidisciplinary Health and Development Study started in 1972.

The group looked for variations in the MAO A genotype in all participants and also periodically assessed the subjects’ history of abuse and criminal convictions, their penchant for violence and any symptoms of antisocial personality disorder.

Symptoms of this antisocial behavior include persistent fighting, bullying, lying, stealing and disobeying the rules during adolescence; as adults, the subjects may repeatedly violate the law, show no remorse for their actions and act impulsively and aggressively.

By age 11, 36 percent of the subjects had been maltreated (8 percent severely), as defined by frequent changes in primary caregiver, rejection by the mother and physical or sexual abuse. Although only 12 percent of the maltreated children had low activity levels of the MAO A, they accounted for 44 percent of their generation’s total convictions for assault and other violent crimes.

“As adults, 85 percent of the severely maltreated children who also had the gene for low MAO A activity developed antisocial outcomes, such as violent criminal behavior,” says Moffitt. “The combination of maltreatment and the genetic variation magnified the odds by nine times.”

On the other hand, the group found that children who had been maltreated but who had higher levels of MAO A were unlikely to develop behavior problems, suggesting that the gene regulating the enzyme does serve a protective function. “The genotype of high MAO A activity,” explains Moffitt, “may promote ‘trauma resistance.'”

Based on these initial findings, Moffitt says, “The combination of the low-activity MAO A genotype and maltreatment predicts antisocial behaviors about as well as high cholesterol predicts heart disease.”

Low levels of the MAO A enzyme may help explain why some abused children are more likely to develop aggressive or criminal behavior, but Moffitt stresses that it does not explain why people are violent: “Low levels of the enzyme did not predict antisocial outcomes in the whole population. It’s relation to aggression only emerged when we considered whether the children had been maltreated.”

However, the UW–Madison researchers suspect that the MAO A genetic variation may play a similar role in protecting people who have experienced other stressful events, such as car accidents or wars.

Besides showing the interaction of the MAO A enzyme and maltreatment on behavior, the group thinks its findings are important for another reason: methodology. Discovering the link between a gene and a disorder is hard, says Moffitt. “This problem has plagued research into genes for schizophrenia, autism, depression and hyperactivity.”

The key to finding the link, she says, is to focus on subjects who share an experience. “If researchers had not noticed that some people exposed to pathogens from mosquitoes escaped malaria, science would never have known about the gene for susceptibility to the disease,” Moffitt explains.

By turning to maltreatment — an environmental pathogen known to bring about antisocial behavior — the UW–Madison researchers were able to identify a genetic variable necessary to solve the equation of why only some maltreated children develop antisocial behavior.