$2.6 Million Grant Funds Study of Early Sex Differences in Human Health, Disease

Nov. 5, 2015


Sex differences in human health and disease are well-documented: autism and attention deficit disorder are much more common in boys, and starting around adolescence, depression is much more common in girls. Recent animal studies suggest that these sex differences may begin in a mother’s womb.
With a $2.6 million grant from the National Institutes of Health, scientists at the University of Rochester School of Medicine and Dentistry will look for an explanation for these differences. Their focus: maternal anxiety during pregnancy. 
Anxiety, defined as excessive worry and the inability to manage or control the worry, is common, and mothers-to-be are no exception. Consistent findings across many studies demonstrate that significant elevations in maternal anxiety during pregnancy can have long-lasting effects on children’s development. The research team, led by Emily S. Barrett, Ph.D., will test the idea that anxiety in pregnancy alters sex hormones in the fetus–how they are produced and how they act–leading to differences in physical, cognitive and social behaviors. The team hypothesizes that these changes may affect males and females differently.

 “There are sex differences in a range of health outcomes and they can be evident very early on, even in infancy,” said Thomas G. O’Connor, Ph.D., professor in the Department of Psychiatry, director of the Wynne Center for Family Research at the University of Rochester Medical Center and a member of the research team. “What’s interesting is that levels of sex hormones are very low in babies, so there must be something happening in utero that is leading to different outcomes in the sexes. We think prenatal maternal anxiety may have some influence.” 

The team will recruit around 290 pregnant women and follow them from the first trimester until their children are 15 months old. They will collect blood and salive samples to measure cortisol -- the primary stress hormone and most robust biomarker of anxiety -- and will administer questionnaires to gauge a woman's level of anxiety throughout her pregnancy.

To understand the activity of sex hormones in utero, the team will measure hormone levels in maternal blood throughout pregnancy, as well as in cord blood (the blood that remains in the umbilical cord following birth). They will also examine genes related to hormone production in the placenta, the organ that allows mom and baby’s bodies to communicate and is considered a valuable window into what takes place before birth.
The investigators will examine the degree to which mothers’ anxiety and sex and stress hormone levels before birth predict specific physical, neurological and social behavior measures at birth, 9 and 15 months of age. The team selected measures that show sex differences in infancy or that have been associated with early sex hormone levels, including mental rotation (the ability to rotate an object in space) and play behavior. The goal is to determine how sex differences in various behaviors can be tied to maternal anxiety in pregnancy.
“This study is important because it will improve our understanding of sex differences in health and disease, which is a priority for the National Institutes of Health,” said Barrett, principal investigator of the study and an assistant professor in the Department of Obstetrics and Gynecology. “In the future, this information could help with the early diagnosis and treatment of conditions that predominantly affect one sex or the other.”
The study will take place over the next five years. In addition to Barrett and O’Connor, Richard K. Miller, Ph.D. and Christopher J. Stodgell, Ph.D. in the Department of Obstetrics and Gynecology, Philip J. Katzman, M.D. in the Department of Pathology and Laboratory Medicine and Sally W. Thurston, Ph.D. in the Department of Biostatistics and Computational Biology will work on the study.