ASPEN, COLO. – A large twin registry study has replicated the findings of an earlier landmark New Zealand study showing that polymorphisms of the monoamine oxidase A gene modify the risk of antisocial behavior in boys exposed to familial adversity, Robert Emde, M.D., said at a psychiatry conference sponsored by the University of Colorado.
“These are impressive studies. They indicate our genetic influences get reordered depending on the environmental circumstances we're exposed to,” observed Dr. Emde, professor of psychiatry and director of the program for early developmental studies at the university in Denver.
The confirmatory work comes from the Virginia Twin Study of Adolescent Behavioral Development, in which Debra L. Foley, Ph.D., and her associates at Virginia Commonwealth University in Richmond reported on 514 male twins aged 8–17 years in the registry (Arch. Gen. Psychiatry 2004; 61:738–44).
All of the twins were genotyped as to their functional polymorphisms of the MAO-A gene and assessed for conduct disorder. The boys and their parents were interviewed regarding the presence or absence of familial adversity as defined by a history of known risk factors for conduct disorder: interparental violence, parental neglect, and inconsistent discipline.
The prevalence of conduct disorder among the boys was 11.5%. The prevalence of any of the low-activity MAO-A alleles previously linked to antisocial behavior was 29.4%. Inconsistent parental discipline was part of the upbringing of 17.3% of the boys, exposure to interparental violence occurred in 2.5%, and parental neglect in 12.6%.
As expected, each of the three familial adversities was independently associated with increased risk of conduct disorder in the boys. The key finding was that a low-activity MAO-A allele was also significantly associated with increased risk of developing conduct disorder, but only in the presence of an adverse childhood environment. A low-activity MAO-A genotype in the absence of familial adversity didn't confer significantly increased risk.
Dr. Emde noted that these findings agree with the Dunedin Multidisciplinary Health and Development Study, a prospective study of 1,037 children born in Dunedin, New Zealand, between April 1972 and March 1973. Only 12% of Dunedin males had both a low-activity MAO-A allele and a prospectively documented history of childhood maltreatment, but they accounted for 44% of court convictions for violent offenses through age 26 years among male study participants, he said at the conference, also sponsored by the Colorado Psychiatric Society and the Denver Institute for Psychoanalysis.
Low-activity MAO-A genotype Dunedin males with probable or severe childhood maltreatment were also 2.8-fold more likely than nonmaltreated males having the low-activity MAO-A polymorphism to be diagnosed with conduct disorder (Science 2002;297:851–4).
In Dunedin, as in the Virginia Twin Study, a low-activity MAO-A genotype in the absence of childhood adversity or maltreatment wasn't associated with significantly increased risk of being diagnosed with conduct disorder.
The Virginia investigators noted that one major implication of the consistent findings in their study and Dunedin is that the search for genetic risk factors for psychiatric disorders is likely to yield inconsistent results unless environmental exposures are also taken into account.
Frederick S. Wamboldt, M.D., said that the Dunedin and Virginia twin studies provide new insight into one of the great debates in psychiatry: the role of nature versus nurture in human development.
“It isn't really genes versus environment, it's genes and environment–but in a complex way. It's not a simple thing,” said Dr. Wamboldt, head of the division of psychosocial medicine at National Jewish Medical and Research Center, Denver, and professor of medicine and of psychiatry at the University of Colorado.