Connors-BRI Symposium

Incorporating Sex as Biologic Variable to Advance Health

May 24, 2021 | 3-5PM

Virtual Event

Hyeonmin Ahn, PhD

Brigham and Women’s Hospital
Women’s Health


Background: Stress exposure triggers changes in hormones (cortisol, ghrelin) and large-scale resting state networks (salience; executive control), each associated with sex differences. However, sex differences in the relationships between hormones and brain connectivity under stress have not been well characterized. We investigated whether there are sex differences in the association between amygdala functional connectivity (FC) and cortisol/ghrelin responses to acute psychosocial stress.

Methods: 34 healthy adults (15F/19M) completed a study visit involving a laboratory psychosocial stress task (Maastricht Acute Stress Test, MAST), followed by a resting-state functional MRI (rs-fMRI) scan. Serial blood draws for assessment of cortisol and ghrelin were collected pre- (T0) and post-MAST (T20 min, T80 min, etc.). Maximum percentage change (MPC) from T0 was calculated for ghrelin and cortisol. rs-fMRI data preprocessing and analysis were performed using CONN.

Results: Post-stress cortisol MPC and ghrelin MPC were not significantly related (r=0.02, p=0.95). Both men and women showed negative correlations between cortisol MPC and amygdala – salience network FC, but with differences in the nodes of the salience network: posterior regions in men [left (r=-0.51) and right (r=-0.49) supramarginal gyrus (SMG); both p<0.05] and prefrontal regions in women (left rostral prefrontal cortex, BA10; r=-0.56, p<0.05). Women, but not men, also showed a negative correlation between cortisol and prefrontal regions of the executive control network (right lateral prefrontal cortex; r=-0.54, p<0.05). In men, ghrelin was positively correlated with amygdala-salience network FC (in a posterior region: right SMG; r=0.47, p<0.05); in women, this relationship was less robust (r=0.38, p=0.163).

Conclusion: We found distinct sex differences in associations between amygdala functional connectivity with large-scale brain networks and stress-related hormones, with stronger patterns in frontal regions for women and posterior regions for men. Further these novel findings provide the opportunity to target the treatments of stress-related psychiatric conditions in a sex-dependent way.

Implication for sex difference and women’s health research: Increased prevalence of stress-related disorders in women compared with men has been well documented; women are approximately twice as likely to be diagnosed with Major Depressive Disorder as men. The observed sex-specific difference may be partly attributed to the effects of sex differences in hormones. In response to acute stress, women have been shown to have greater hyperactivation of amygdala than men, while men showed higher cortisol response than women. Here, we sought to identify whether there are sex differences in neural networks that are functionally linked with stress-related hormones, including ghrelin, which has recently been implicated in the response to stress and has shown sex differences in secretory dynamics. Our findings provide novel evidence of sex differences in the association between these hormones and amygdala-salience/executive network connectivity, highlighting new pathways to target for treatment of stress-related psychiatric conditions.


3PM – Welcome Remarks
3:05PM – Keynote Address
3:45PM – Featured Short Talks
4:20PM – Lightning Talks
4:50PM – Closing Remarks

Keynote Speaker

Janine Austin Clayton, MD

Janine Austin Clayton, M.D., Associate Director for Research on Women’s Health and Director of the Office of Research on Women’s Health (ORWH) at the National Institutes of Health (NIH), is the architect of the NIH policy requiring scientists to consider sex as a biological variable across the research spectrum. This policy is part of NIH’s initiative to enhance reproducibility through rigor and transparency. As co-chair of the NIH Working Group on Women in Biomedical Careers with NIH Director Dr. Francis Collins, Dr. Clayton also leads NIH’s efforts to advance women in science careers.

Prior to joining the ORWH, Dr. Clayton was the Deputy Clinical Director of the National Eye Institute (NEI) for seven years. A board-certified ophthalmologist, Dr. Clayton’s research interests include autoimmune ocular diseases and the role of sex and gender in health and disease. She is the author of more than 120 scientific publications, journal articles, and book chapters.
Dr. Clayton, a native Washingtonian, received her undergraduate degree with honors from Johns Hopkins University and her medical degree from Howard University College of Medicine. She completed a residency in ophthalmology at the Medical College of Virginia. Dr. Clayton completed fellowship training in cornea and external disease at the Wilmer Eye Institute at Johns Hopkins Hospital and in uveitis and ocular immunology at NEI.

Dr. Clayton has received numerous awards, including the Senior Achievement Award from the Board of Trustees of the American Academy of Ophthalmology in 2008 and the European Uveitis Patient Interest Association Clinical Uveitis Research Award in 2010. She was selected as a 2010 Silver Fellow by the Association for Research in Vision and Ophthalmology. In 2015, she was awarded the American Medical Women’s Association Lila A. Wallis Women’s Health Award and the Wenger Award for Excellence in Public Service. Dr. Clayton was granted the Bernadine Healy Award for Visionary Leadership in Women’s Health in 2016. She was also selected as an honoree for the Woman’s Day Red Dress Awards and the American Medical Association’s Dr. Nathan Davis Awards for Outstanding Government Service in 2017.