More and more women are taking antidepressants—particularly selective serotonin reuptake inhibitors (SSRIs)—during pregnancy, and many in the field consider this safe. However, some studies, including a new paper published in JAMA Pediatrics by researchers at Columbia University Vagelos College of Physicians and Surgeons, suggest that SSRIs may affect emotional learning, potentially raising the risk of depression later during puberty. We asked the study leaders, Jonathan Posner, MD, and Jay Gingrich, MD, PhD, about the latest research on the risks and benefits of these drugs during pregnancy.

What does the latest research say about the effect of prenatal antidepressant exposure on children?

Posner: The evidence in humans is limited and unclear. A few studies concluded that SSRIs have little or no impact on children. But this may be because they didn’t focus on adolescence, when animal data suggest that the effects begin to emerge.

Gingrich: Our mouse studies, dating back to 2004, show that inhibiting the uptake of the neurotransmitter serotonin—which is what SSRIs do—during pregnancy has profound effects on fetal brain circuitry. But we don’t see behavioral changes in these mice right away. In mice, it looks like SSRIs set the stage for increased anxiety and depressive-like behaviors that emerge later in adolescence.

Indeed, we observed this delayed effect in a prior study of health records from more than 15,000 people in Finland. We found that rates of depression in early adolescence were two to three times higher among those who had prenatal exposure to SSRIs compared with those who did not.

What’s happening to their brains that might explain this connection?

Posner: That was the focus of our new study, in which we performed MRIs on infants born to mothers with depression, including those who had been treated with SSRIs and those who had not.

In the infants with prenatal SSRI exposure, we found significant increases in the volume of the amygdala and the insula and increased connectivity between those brain regions.

Gingrich: The amygdala and the insula play a critical role in emotional processing. We see these changes in mice after early-life SSRI exposure and have tied these changes to behavioral abnormalities that appear later in adolescence.

What can you recommend to expectant mothers struggling with depression, and how should these findings be used by their doctors?

Posner: It’s a difficult clinical decision. We know that maternal depression in and of itself can impact the health of the fetus and the relationship between mother and infant. So, doing nothing is not necessarily the answer. But other interventions, such as non-SSRI antidepressants and psychotherapy, can help depressed moms get through pregnancy.

Gingrich: Our mouse studies suggest that the timing of SSRI use matters tremendously. There appears to be less risk in the first and second trimesters. So perhaps you could reduce the dose during the third trimester or switch to a non-SSRI antidepressant. We’ve tested non-SSRI antidepressants in mice and they don’t seem to have any effect on the developing brain.

What needs to be done to get more definitive answers?

Posner: A long-term clinical study, in which we would randomize pregnant women with depression to SSRIs or other therapies and then follow their children through adolescence, would be ideal, but that is not an easy undertaking. Instead, we can engage in a combination of epidemiologic, rodent, primate, and human studies to identify the biological steps leading from prenatal SSRI exposure to depression in adolescence.

It’s critical that we find more answers. Our new findings suggest that SSRIs may be having an effect on offspring, but more research is needed to confirm that. This is not an insignificant problem. Studies show that 8% to 10% of women in the US use SSRIs during pregnancy, which means that between 300,000 and 400,000 kids are being exposed to these drugs each year. If we’re doubling or tripling the rate of depression in these children, from 20%, to 40%, or 60%, that’s adding a significant burden of unnecessary depression.