ECHO PATHWAYS investigators conducted a study of serum sex hormones in pregnant women and child behavioral assessments in the TIDES cohort, to be published in the March 2020 issue of Psychoneuroendocrinology. Estrogen and testosterone are known to play a key role in the fetal development of sex-differentiated brain structures and reproductive behaviors, but their role in the development of psychopathologic behaviors is not well understood. This TIDES study is the first study to use healthy pregnancies to evaluate maternal blood testosterone and multiple forms of estrogens as they relate to several dimensions of psychopathologic behavior in 4- to 5-year-old children: externalizing behaviors like aggression, internalizing behaviors like depression, adaptive skills, autism-related behaviors, and behaviors related to attention problems and withdrawal. We observed that maternal blood testosterone in early pregnancy was associated with increased internalizing behaviors and behaviors relating to attention problems and withdrawal for both boys and girls. Also, we observed that maternal blood estrone, a less potent form of estrogen, was associated with worse adaptive skills in girls. The association between testosterone and internalizing behaviors but not externalizing behaviors is surprising, and these findings may reflect complex sex hormone signaling and transformation on both the maternal and fetal sides of the womb that still remains to be fully characterized. These novel results suggest that normal variation in testosterone or estrogen in healthy pregnancies can influence the development of psychopathologic behaviors, and it offers clues into how factors that may affect those hormones may also influence behavioral development. Dr. Sheela Sathyanarayana, ECHO PATHWAYS PI, was senior author and Dr. Drew Day, ECHO PATHWAYS epidemiologist, was first author on this paper.
