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Understanding the Depression Gender Gap

Doctoral student Zachary Rosinger and colleagues found that the hypothalamus (where the stress pathway begins) was more vulnerable to stress chemicals being released in females than in males.

ALBANY, N.Y. (Aug. 29, 2017) — In the United States, women are twice as likely as men to be diagnosed with a form of depression, according to the Mayo Clinic. The stress and anxiety gender gap exists in similar ratios all over the world.

Discovering the biological roots of such a stark difference based on one’s sex is comprises the key motivation for doctoral student Zachary Rosinger’s work in Damian Zuloaga’s lab.

Zuloaga, an assistant professor of psychology, specializes in behavioral neuroscience. He and his team of researchers are interested in the stress response pathway and how it is regulated by sex hormones, with the goal of better understanding how men and women are differentially impacted by stress.

Rosinger, Zuloaga and colleagues from UAlbany and the University of Texas have just published their findings on how a chemical released in the brain may contribute to observed age- and sex-dependent differences in stress regulation. Their article in the journal Neuroscience is now available online.

When someone experiences stress, physical or psychological, they release a chemical called corticotropin-releasing factor (CRF). After it is released, it binds to its receptor, CRF receptor 1 (CRFR1) to trigger the rest of the stress response.

Doctoral student Zachary Rosinger
Doctoral student Zachary Rosinger

"There is currently a lack of information regarding CRFR1 distribution throughout the mouse brain, which led to our investigation," said Rosinger. "We chose development because it is a time in which the brain is more vulnerable to environmental influence, and may likely shape how the developed brain functions in response to adulthood stressors."

As Rosinger points out, the work done in mice provides a method for the research to be eventually translated to human medicine.

"Our investigation uncovered many differences across development, suggesting that different portions of the brain are vulnerable to CRF at different time points. When we discovered a clear sex difference in the expression of CRFR1 for one region of the brain, we got very excited," said Rosinger.

The region where the difference was found? The hypothalamus, a small yet vitally important part of the brain that serves as a critical link between the nervous system and the endocrine system by way of the pituitary gland.

In their findings, the researchers found numerous cells affected by CRFR1 present in females and are largely absent in males.

"This means that one part of the brain is vulnerable to stress chemicals being released in females and not in males. We think we are onto something, because this brain region is located within the hypothalamus, which is where the stress pathway begins," said Rosinger.

Going forward, the researchers hope to get a better understanding of how this difference in CRFR1 forms, as well as how this difference may impact anxiety- and depression-like behavior in males and females. Their discovery could also potentially open doors up for future therapeutic targets, and to better understand and treat these difficult conditions.

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