Normal hormone levels trigger severe depression in some women; researcher discovers mechanism

(Press-News.org) CHAPEL HILL, North Carolina, USA, 29 July 2025 – In a wide-ranging Genomic Press Interview published today in Brain Medicine, Dr. David R. Rubinow recounts the serendipitous path that led him to overturn decades of medical assumptions about hormone-related mood disorders in women.

The interview reveals how a chance phone call accepting a fellowship position he had initially rejected set Dr. Rubinow on a trajectory that would fundamentally change how medicine understands and treats reproductive mood disorders. His discovery that women with conditions like premenstrual dysphoric disorder (PMDD), postpartum depression, and perimenopausal depression have completely normal hormone levels challenged the prevailing wisdom of an entire field.

The Power of Saying Yes

"I called him right back and said that I would be grateful to accept his invitation," Dr. Rubinow recalls of the moment that changed his career trajectory. That decision to work with Dr. Bob Post at the National Institute of Mental Health launched a 27-year career at NIH that would validate the experiences of millions of women whose hormone-related mood symptoms had been dismissed or misunderstood.

Through meticulous research involving blinded hormone manipulation studies, Dr. Rubinow and colleague Dr. Peter Schmidt identified what they termed "differential sensitivity" – the phenomenon where susceptible women respond differently to normal hormonal fluctuations. This breakthrough shifted treatment approaches from attempting to normalize hormone levels to targeting the abnormal response mechanisms themselves.

From Bench to Bedside

The practical impact of Dr. Rubinow's work materialized when his insights contributed to developing brexanolone (Zulresso), the first FDA-approved medication specifically for postpartum depression. Unlike traditional antidepressants, this neurosteroid treatment directly addresses the differential sensitivity mechanisms his research had uncovered.

In the interview, Dr. Rubinow shares how his background in philosophy and history unexpectedly prepared him for scientific discovery. "What I enjoyed in those two areas were the discipline of questioning in philosophy and the opportunity for creative linking of ideas in history," he explains. This interdisciplinary thinking enabled him to identify novel connections that yielded significant physiological insights.

Building Legacy Through Leadership

After establishing himself as a researcher, Dr. Rubinow brought his vision to the University of North Carolina at Chapel Hill in 2006, serving as Chair of Psychiatry until 2019. During his tenure, he founded the UNC Center for Women's Mood Disorders, established (with Samantha Meltzer-Brody) the nation's first peripartum psychiatry inpatient unit, and created (with Susan Girdler) the first NIH-sponsored fellowship in women's mood disorders.

The interview also reveals Dr. Rubinow's parallel passions for music and woodworking, offering glimpses into the person behind the scientific achievements. His philosophy of "bringing the chisel when sent for the hammer" – inherited from his grandfather – reflects the thoughtful, comprehensive approach that characterized his research career.

Recognition and Reflection

A member of the National Academy of Medicine since 2012 and past president of both the Society of Biological Psychiatry and the American College of Neuropsychopharmacology, Dr. Rubinow has authored over 400 scientific publications. Yet in the interview, he attributes much of his success to serendipity and being open to unexpected opportunities.

His work has particular relevance as awareness of women's mental health continues to grow. By establishing reproductive psychiatry as a legitimate subspecialty with evidence-based treatments, Dr. Rubinow's research has provided hope and validation for women whose experiences were previously marginalized in medical settings.

Dr. David R. Rubinow's Genomic Press interview is part of a larger series called Innovators & Ideas that highlights the people behind today's most influential scientific breakthroughs. Each interview in the series offers a blend of cutting-edge research and personal reflections, providing readers with a comprehensive view of the scientists shaping the future. By combining a focus on professional achievements with personal insights, this interview style invites a richer narrative that both engages and educates readers. This format provides an ideal starting point for profiles that explore the scientist's impact on the field, while also touching on broader human themes. More information on the research leaders and rising stars featured in our Innovators & Ideas – Genomic Press Interview series can be found in our publications website: https://genomicpress.kglmeridian.com/.

The Genomic Press Interview in Brain Medicine titled "David R. Rubinow: Triggers and susceptibility–reproductive steroids and the regulation of affective state," is freely available via Open Access on 29 July 2025 in Brain Medicine at the following hyperlink: https://doi.org/10.61373/bm025k.0089.

About Brain Medicine: Brain Medicine (ISSN: 2997-2639, online and 2997-2647, print) is a peer-reviewed medical research journal published by Genomic Press, New York. Brain Medicine is a new home for the cross-disciplinary pathway from innovation in fundamental neuroscience to translational initiatives in brain medicine. The journal's scope includes the underlying science, causes, outcomes, treatments, and societal impact of brain disorders, across all clinical disciplines and their interface.

Visit the Genomic Press Virtual Library: https://issues.genomicpress.com/bookcase/gtvov/

Our full website is at: https://genomicpress.kglmeridian.com/

END