Genetic Variation in Depressed Mothers Tied to Psychiatric Illnesss in Children

There appears to be a strong relationship between oxytocin dysfunction and adverse social outcomes, according to a study published July 12 in AJP in Advance.

Ruth Feldman, Ph.D., a professor of psychology at University Bar-Ilan in Israel, and colleagues at National University of Singapore found that variations in the allele of the oxytocin receptor gene (OXTR) may be a cause of long-term psychiatric disorders in children of women who suffer from postpartum and chronic depression.

Using the Beck Depression Inventory, the researchers evaluated 46 chronically depressed mothers who reported depressive symptoms two days after giving birth and compared them with 103 mothers reporting no depression. Six years later, children from each group were assessed for psychiatric disorders, social engagement, and empathy.

Results showed that 61 percent of children of depressed mothers were diagnosed with Axis I disorders using DSM-IV criteria; they primarily had anxiety, oppositional defiance, and attention-deficit/hyperactivity disorders.

In addition, the 6-year-olds displayed low levels of social engagement and empathy. Children of nondepressed mothers were four times less likely to develop psychopathologies and were more likely to be socially interactive and empathetic than those who mothers had depression.

“These are amazingly high numbers [associated with maternal depression] when there are no other comorbid conditions,” Feldman told Psychiatric News. She explained that all mothers in the study were required to be middle class, physically healthy, over age 21, and in a committed relationship and to have given birth at full term. These requirements were intended to eliminate factors that might contribute to chronic depression in mothers and adverse psychosocial patterns in children. “The study tapped only the effects of maternal depression per se,” she said.

Expanding beyond behavioral studies, the researchers investigated the significance of the oxytocin system in the setting of maternal depression. Oxytocin is a neurohormone that plays a key role in mammalian reproduction and is a predictor for major consequences in human social bonding, including intimate relationships and parent-child interaction.

Previous studies have linked adverse social outcomes in humans with low oxytocin levels and nucleotide variance among OXTR genes—in particular, the OXTR rs2254298 polymorphism.

Individuals possessing a single G variant of the OXTR rs2254298 polymorphism are at greater risk for autism and major depressive disorder, and those possessing two copies, the GG variant, are more likely to have emotional detachment. However, the presence of the A variant is associated with heightened emotional security. AA homozygous trait carriers have been shown to exhibit social synchrony and physical affection because they have higher levels of oxytocin.

To assess the impact of oxytocin levels and receptor variations on maternal depression and Axis I disorders in the offspring, Feldman and colleagues analyzed saliva from the mother and child pairs.

Data showed that depressed mothers and their children had significantly lower oxytocin levels and a greater incidence for the GG trait when compared with families of nondepressed mothers. Among the depressed mothers, the presence of the GG allele correlated with a 62 percent occurrence of child Axis I disorders, whereas the possession of a single A or AA allele, regardless of depression state, decreased the offsprings’ psychopathologies by at least half.

“What’s amazing is that this study is exquisitely sensitive to epigenetic effects,” said Eric Hollander, M.D., director of the Compulsive, Impulsive, and Autism Spectrum Disorder Program at Albert Einstein College of Medicine. “It’s seems that having the resilience [AA] allele, rather than the pathological [GG] allele, is more important, because the presence of the A allele rescued children of depressed mothers from psychiatric disorders,” he told Psychiatric News. Hollander was one of the first clinicians to show that oxytocin administration can alleviate adverse behaviors in humans in a 2003 study published in Neuropsychopharmacology.

As for Feldman, she is confident that her research will contribute to the implementation of “oxytocinergic” therapies for postbirth maternal depression, which affects 15 percent to18 percent of women in industrial societies. She concluded that researchers should search for biomarkers and positive environmental factors that reduce long-term adverse effects of maternal depression to provide affected children a better opportunity to adapt to their social world. ■