Exposure to maternal prenatal depression represents one of the most common forms of early adversity. In the United States, approximately one in five infants is exposed to elevated maternal depressive symptoms, with most depressed women remaining untreated during pregnancy. Exposure to maternal depressive symptoms and prenatal major depressive disorder have been associated with adverse physical health and behavioral outcomes across development, including preterm delivery, low birth weight, and alterations in fetal heart rate and activity in the fetal period, and alterations in brain structure, cognition, and growth from the newborn period into childhood. However, despite relatively consistent associations across development, the mechanism and moderators of long-term outcomes after exposure to maternal depression remain unclear.
[Photo: Dr. Laura Stroud]
Fetal programming of offspring brain and stress systems is a prominent proposed mechanism underlying links between prenatal adversity and offspring health and behavioral outcomes. In particular, placental enzymes regulating maternal-fetal glucocorticoid and serotonin transfer have been proposed as key modulators of fetal programming effects of maternal depression. The purpose of this study, led by Dr. Laura Stroud, associate professor of behavioral and social Sciences and faculty member in the Centers for Behavioral and Preventative Medicine, was to test the association between maternal prenatal major depressive disorder and infant cortisol regulation, as well as evaluate placenta glucocorticoid and serotonin signaling as moderators of this relationship. Participants were 153 mother-infant pairs from a low-income, diverse sample. Participants were categorized as having prenatal major depressive disorder, preconception-only major depressive disorder, or no major depressive disorder (controls).
The researchers found that daughters of mothers with prenatal major depressive disorder had 51% higher baseline and 64 percent higher stress response cortisol than daughters of controls, and 75 percent higher stress-responsive cortisol than daughters of mothers with preconception-only major depressive disorder. Methylation of HSD11B2, a regulator of fetal glucocorticoid exposure, moderated links between prenatal major depressive disorder and cortisol, with 1 percent methylation decreases associated with 9 percent increased baseline cortisol in infants of mothers who had prenatal major depressive disorder. The expression of SLC6A4, a gene which encodes the serotonin transporter, moderated links between prenatal major depressive disorder and cortisol response among boys alone, with 10-fold increases in expression associated with threefold increases in stress-responsive cortisol in sons of control mothers.
The results of this study highlight the specificity of associations between prenatal and preconception major depressive disorder and cortisol regulation, and the importance and complexity of placenta glucocorticoid and serotonergic pathways underlying the intergenerational transmission of risk from maternal adversity.
This study was published in Psychosomatic Medicine, Volume 78, Issue 92016.
For more information: https://www.ncbi.nlm.nih.gov/pubmed/27763986