Elizabeth LucasA UAB assistant professor in the Department of Psychiatry and Behavioral Neurobiology has received a $3.5 million grant to study how hormones influence the female brain’s response to trauma. , Ph.D., assistant professor in the University of Alabama at Birmingham Marnix E. Heersink School of Medicine, Department of Psychiatry and Behavioral Neurobiology, recently received a $3.5 million grant to study post-traumatic stress disorder, or PTSD, in women.

“Women are twice as likely as men to be diagnosed with PTSD,” Lucas said. “They also tend to have higher rates of anxiety and depression compared to men with PTSD.”

Filling the research gap 

The amygdala, a part of the brain that processes emotions, plays a key role in how people respond to both positive and negative experiences. It acts as an emotional radar, helping the body determine whether something is good or bad and signaling how to respond.

Research has shown that female hormones, particularly one called estradiol, affect how the amygdala functions. When estradiol levels are high, such as during the ovulatory phase of the menstrual cycle, women tend to feel less negative and more positive.

Until now, no research has examined how certain brain cells behave differently in men and women or how hormones influence those changes. Lucas’ study will explore how brain cells in the amygdala differ between men and women and how they fluctuate throughout the female reproductive cycle.

The research will focus on Rspo2 neurons, which are linked to negative emotions, and interneurons, which control other brain cells, including Rspo2 neurons. These cells contain receptors for estradiol, meaning they respond to this hormone. Lucas believes these cells work together in a unique way to influence how people respond to positive and negative experiences.

According to Lucas, the study has three primary goals:

• Explore how estradiol changes this brain circuit using advanced neuroscience tools.
• Test how these changes affect positive and negative emotions.
• Determine how estradiol may protect against the development of PTSD symptoms after a traumatic event.

If successful, this research could explain why women respond differently to stress depending on their hormone levels and could lead to better treatments for PTSD and related disorders such as anxiety and depression.

The role of valence processing 

Valence processing is the way the brain determines whether an experience feels good or bad. Positive valence experiences make a person feel happy, excited or safe. Negative valence experiences can cause fear, sadness or stress.

PTSD occurs after a person experiences an extremely negative event, or trauma. However, not everyone who experiences trauma develops PTSD. Lucas says she believes the way the brain processes trauma may help predict whether someone develops PTSD.

“Once a person is diagnosed with PTSD, they often feel scared or anxious even when they are safe,” Lucas said. “They can be triggered by reminders of the trauma, which causes negative valence to take over the brain. It is like being stuck in a constant state of panic.”

Why studying the female brain matters 

Lucas says there is still much to learn about the female brain, especially regarding hormones.

“We know very little about how ovarian hormones enter the brain and affect its function,” Lucas said. “This process changes across the menstrual cycle, but we do not fully understand how it works on a biological level.”

Lucas says she is most excited about using this study to connect patient observations with biological research.

“We know women are more susceptible to PTSD and that symptoms are influenced by hormone changes across the menstrual cycle,” she said. “What we don’t know is how this happens. Our goal is to uncover the biological mechanisms behind these observations. Once we understand that, we can begin developing therapeutic tools to improve treatment options.”