Prenatal Stress, Gene Variant Interact To Raise Conduct Disorder Risk

Prenatal stress can contribute to development of conduct disorder in children if they possess a particular variant of the dopamine receptor gene, a study published online September 14 in the Journal of Child Psychology and Psychiatry suggests.

The lead researcher was Katrin Zohsel, Ph.D., of the Central Institute of Mental Health in Mannheim, Germany. Adelaide Robb, M.D., a professor of psychiatry and pediatrics at George Washington University, told Psychiatric News that she found the study interesting because the results suggest that “reduction in prenatal stress might be a primary-prevention measure for the development of externalizing disorders.”

The study subjects were women who had recently given birth and who were more likely to have children who would eventually develop conduct disorder on the basis of various risk factors that the mothers possessed—for example, a low educational level, a history of family adversity, being a single parent, or experiencing obstetric complications.

Three months after the women gave birth, the researchers used a standardized parent interview instrument to assess the extent of their prenatal anxiety and symptoms of depression.

The researchers also genotyped the children to see which variant of the dopamine receptor gene they possessed, since one of the variants—7r—had been shown in other research to confer susceptibility to developing externalizing behaviors, especially in the presence of adverse environmental factors. Out of the 308 children, 182 had no 7r variant, 103 had one 7r variant, and 23 had two 7r variants.

The researchers followed the children to age 15 to see how many developed DSM-IV conduct disorder and/or oppositional defiant disorder. A total of 102 of the children—a third of those studied—did develop the disorder. Significantly more boys than girls warranted such diagnoses.

The researchers then evaluated whether prenatal stress alone or in combination with the dopamine receptor gene variant 7r had any influence on whether the children developed conduct disorder and/or oppositional defiant disorder. During the analyses, potential confounders, such as maternal smoking during pregnancy, psychosocial adversity, and postpartum depression were considered.

When children had been exposed to prenatal stress, but did not have any copies of the 7r gene variant, they were not at a significantly higher risk of developing conduct disorder and/or oppositional defiant disorder. But when they had been exposed to prenatal stress and possessed one or two copies of the 7r variant, they were at increased risk of having conduct disorder and/or oppositional defiant disorder.

“We were quite surprised to find (in a subgroup of children) an effect of the prenatal environment on an outcome that was measured many years after pregnancy,” Zohsel told Psychiatric News. “Even more surprising was the fact that the interaction effect of prenatal maternal stress and the dopamine receptor gene on externalizing behavior turned out to be stable after controlling for many possible confounders such as the distress that mothers were undergoing shortly after birth and throughout the childhood of their offspring.”

Thus, “prevention of childhood antisocial behavior may start as early as pregnancy,” Zohsel asserted. “Although measures reducing prenatal maternal stress—such as counseling for risk groups, stress management training, treatment of psychiatric problems during pregnancy—may not be effective in reducing antisocial behavior problems in all children, this might be the case in subgroups of children with a certain genotype. Clinical studies assessing this assumption would be desirable.”

The study was funded by the German Research Foundation. ■

An abstract of “Mothers’ Prenatal Stress and Their Children’s Antisocial Outcomes—A Moderating Role for the Dopamine D4 Receptor (DRD4) Gene” is posted at http://onlinelibrary.wiley.com/doi/10.1111/jcpp.12138/abstract.