Prenatal antidepressants seem not to affect child
Friday, January 12, 2007

By David Douglas

NEW YORK (Reuters Health) - The use of antidepressant drugs during pregnancy does not appear to have a significant effect on the behavior of the child, Canadian and Korean researchers report in the Archives of Pediatrics and Adolescent Medicine.

Dr. Tim F. Oberlander of the University of British Columbia, Vancouver and colleagues compared behaviors of 22 children who were prenatally exposed to a selective serotonin uptake inhibitor (SSRI), one of a relatively new class of antidepressant drugs including Prozac and Zoloft, along with 14 unexposed children.

The researchers evaluated data for the children, all of whom were 4 years of age, using a combination of parent reports and direct observations of the child's activities.

"We observed that while the behaviors reported by the mothers did not differ between the two groups," Oberlander told Reuters Health, mothers experiencing mood problems were more likely to report increased activity and poor attention in their child.

On direct observation in the laboratory, he added, "inattentiveness was more common in exposed children. We also observed increased aggressive behaviors in children who had had withdrawal symptoms in the newborn period." However, the differences were not statistically significant.

Overall, said Dr. Oberlander, "the best predictors of attentional problems at age 4 were current reports of maternal mood and parental stress," regardless of SSRI treatment or depression during pregnancy.

Nevertheless, he added, it is still uncertain if "withdrawal behaviors in the newborn period can be excluded as a possible predictor of attentional problems in 4-year-olds with prenatal SSRI exposure."

Furthermore, Oberlander concluded, these findings suggest that despite prenatal antidepressive drug treatment during pregnancy, the "mothers' mental health continues to influence child development and behavior long after birth."

SOURCE: Archives of Pediatrics and Adolescent Medicine, January 2007.

Serotonin (5-HT) acts as a neurotransmitter, but also modulates brain maturation during early development. The demonstrated influence of genetic variants on brain function, personality traits, and susceptibility to neuropsychiatric disorders suggests a critical importance of developmental mechanisms. However, little is known about how and when developmentally perturbed 5-HT signaling affects circuitry and resulting behavior. The 5-HT transporter (5-HTT) is a key regulator of extracellular 5-HT levels and we used pharmacologic strategies to manipulate 5-HTT function during development and determine behavioral consequences. Transient exposure to the 5-HTT inhibitors fluoxetine, clomipramine, and citalopram from postnatal day 4 (P4) to P21 produced abnormal emotional behaviors in adult mice. Similar treatment with the norepinephrine transporter (NET) inhibitor, desipramine, did not adversely affect adult behavior, suggesting that 5-HT and norepinephrine (NE) do not share the same effects on brain development. Shifting our period of treatment/testing to P90/P185 failed to mimic the effect of earlier exposure, demonstrating that 5-HT effects on adult behavior are developmentally specific. We have hypothesized that early-life perturbations of 5-HT signaling affect corticolimbic circuits that do not reach maturity until the peri-adolescent period. In support of this idea, we found that abnormal behaviors resulting from postnatal fluoxetine exposure have a post-pubescent onset and persist long after reaching adult age. A better understanding of the underlying 5-HT sensitive circuits and how they are perturbed should lead to new insights into how various genetic polymorphisms confer their risk to carriers. Furthermore, these studies should help determine whether in utero exposure to 5-HTT blocking drugs poses a risk for behavioral abnormalities in later life.

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Conclusion
Our findings demonstrate that 5-HT signaling during early life has important effects on adult behavior that are not shared by NE. The developmental period sensitive to 5-HT perturbation approximately corresponds to the human third trimester and lasting up to the first years of life.

Our observations suggest that human exposure to 5-HTT inhibitors during early life (e.g., pregnancy or breast-feeding) might exert similar effects to those described here for mice. However, with breast feeding, infant exposure levels are far less than those occurring during pregnancy (Suri et al., 2002Go; Stowe et al., 2003Go; Berle et al., 2004Go) and are therefore likely to be less significant in their impact on brain development. Ultimately, understanding the effects of perturbed 5-HT signaling on CNS circuit development may provide useful insights into the mechanism by which genetic variants predispose to affective disorders and allow a better understanding of the safety of early-life exposure to 5-HTT inhibitors.