09:51pm Thursday 04 June 2020

Sex Differences in Fetal Brain Development May Explain Risk of Co-Occurring Depression and Cardiovascular Disease

Co-occurring depression and cardiovascular disease is significantly more common in women than in men  and will be the number one cause of disability worldwide by 2020. The study was presented December 4, at the American College of Neuropsychopharmacology (ACNP) Annual Meeting.

Led by Jill Goldstein, PhD, director of research at the Connors Center for Women’s Health and Gender Biology at BWH, the research team found that adult women who were exposed  to preeclampsia, a pregnancy condition marked by a mother’s high blood pressure, or to conditions that restricted fetal growth during their prenatal development, were at significantly higher risk for the co-occurrence of depression and cardiovascular disease during adulthood.  Specifically, the researchers found that disruption during fetal development of the autonomic nervous system, the part of the central nervous system in the brain that helps regulate heart rate, is a risk factor for cardiovascular disease during adulthood .

“Understanding the early signs and pathways to this common co-occurrence will help us think about how we can intervene earlier, before adult onset of these disorders occurs,” said Goldstein.

This research expands on a National Institutes of Health (NIH) cohort study that systematically followed mothers through pregnancy and their children through the first seven years of life. During pregnancy, mothers’ blood was taken and stored at NIH for 40 years. Over the last 20 years, Goldstein and her colleagues have followed many of the adult offspring from this cohort into their late 40s.

In this study, Goldstein and her colleagues analyzed the mothers’ prenatal blood and identified indicators of immune activation (associated with preeclampsia and fetal growth restriction) to which the developing fetus was exposed. They looked at the impact of these immunological indicators on the development of the stress response circuitry in the male and female offspring’s brain. Stress response circuitry includes brain regions that show some of the largest sex differences in the brain.  These regions develop differently in males and females during fetal development and function differently in men and women in adulthood.

Given that these brain regions also regulate mood and cardiac function, Goldstein hypothesized that disruptions in the development of this brain circuitry during fetal development would result in the sex-specific vulnerability to depression and cardiac disease in adulthood.

Goldstein and her colleagues re-recruited adults who were exposed to prenatal immune activation, as well as unexposed adult siblings, to look at how these potential vulnerabilities developed over 40-50 years. Psychiatric interviews, cognitive testing, electrocardiocardiogram data, and blood were collected.  Participants also underwent functional brain imaging using a stress challenge task, during which hormones and heart rate measures were collected. 

Results showed significant associations between mother’s immunologic responses during fetal development and sex-specific deficits in exposed adults’ stress response brain activity, hormones and cardiac dysregulation 40 years later.

The studies were funded by the National Institute of Mental Health and NIH Office of Research on Women’s Health. 

Press release written and distributed by the American College of Neuropsychopharmacology.

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