SUNY Downstate Publishes New Study In Brain Research Linking Stress Resilience To Prevention of Psychiatric Disorders
By SUNY Downstate Press Office | Sep 10, 2025
Brooklyn, NY – SUNY Downstate Health Sciences University today announced the publication of a new study in Brain Research, a peer-reviewed neuroscience journal. The study, titled Sex differences in resilience at puberty depend upon divergent effects of a stress steroid at α4βδ GABA-A receptors, was led by Sheryl Smith, Ph.D., a distinguished professor at SUNY Downstate Health Sciences University.
Developing resilience is a critical skill to deal with the stress of daily life. The study demonstrates how adolescent stress resilience improves mental health in adulthood. Using a rodent model, internationally known neuroscience researcher Dr. Smith, identified a novel sub-type of GABA-A receptor, α4βδ, which emerges in the brain at puberty and is a target for the stress steroid allopregnanolone.
"It is surprising that predictable, mild stress results in resilience. This suggests that some forms of stress may actually be beneficial for mental health. It was also not expected that allopregnanolone would produce different effects in two areas of the brain that play a role in stress responses, but this dual effect allowed for the development of resilience,” said Dr. Smith. “Depression affects 18-20 percent of the population. Our results may suggest a novel therapeutic use for allopregnanolone during adolescence beyond its current use for post-partum depression, which would impact mental health even in adulthood.”
The paper represents the thesis work of first author Lindsay Kenney, Ph.D., a medical student at Downstate. She and the research team evaluated stress resilience using the forced swim test, which measures swimming, floating, and escape behaviors during a four-minute trial following a two-week program of daily, predictable restraint stress. Resilience, the ability of the mice to recover from stress, emerged only in pubertal female mice. When the stress steroid allopregnanolone was released during the test, it produced a 50 percent increase in coping behavior in this group.
However, male and adult female mice did not show improved coping in response to the same stressor. In addition to behavioral tests, researchers used state-of-the-art confocal microscopy and stacked image acquisition. This allowed them to visualize α4βδ GABA-A receptors and nerve cell connections in the brain, which exhibit an inverse relationship when interacting with allopregnanolone. These results are consistent with prior research that finds increased activity of the prefrontal cortex and reduced activity of the amygdala are associated with improved resilience.
Ultimately, adolescent girls respond to stress and experience depressive symptoms more than adolescent boys. Since 1 in 5 adolescents experience these symptoms, this study suggests that exposure to predictable stress may serve as a novel therapeutic approach to prevent future psychiatric disorders in adulthood.
The full study is available in the October edition of the Brain Research Journal, and can be accessed here.
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About SUNY Downstate Health Sciences University
SUNY Downstate Health Sciences University, located in Brooklyn, is one of four academic
medical centers in the 64-campus SUNY system, and the only one in New York City. With
a mission to educate health professionals, advance research, and provide care to Brooklyn’s
2.7 million residents, Downstate is deeply rooted in its community.
Its teaching hospital, University Hospital at Downstate (UHD), offers high-quality, comprehensive care across 53 specialties and subspecialties. UHD is home to Brooklyn’s only kidney transplant program and is recognized for excellence in high-risk neonatal care, pediatric nephrology, and dialysis.
Downstate also encompasses five schools: Medicine, Nursing, Health Professions, Graduate Studies, and Public Health. It fosters biotech innovation through its Biotechnology Incubator and BioBAT and is committed to #KeepCareClose for the communities it serves through its clinical, academic, and research missions. Click here for more information.