In a first-of-its-kind study comparing younger and older biological females, researchers at the University of Arizona examine how shifts in estrogen levels can alter the brain’s fear-circuitry — offering new insights into why some women recover from trauma while others develop post-traumatic stress disorder.
The Neuroimaging Study of Fear Learning, led by principal investigator Ashley Huggins, Ph.D., from the department of psychology at the UA, uses advanced brain imaging to uncover how fear is processed differently across the female lifespan.
Huggins’ study is part of the Cognition, Affect and Traumatic Stress Lab, which aims to improve mental health outcomes for trauma survivors by identifying the biological mechanisms behind PTSD.
Prior to 1980, it wasn’t widely acknowledged that women could even be diagnosed with PTSD. Most early researchers on trauma and PTSD focused solely on samples of men, specifically men who were in combat. Recognition of symptoms related to sexual trauma led to increased research on women’s experiences.
Now, the American Psychological Association recognizes a profound disparity — biologically female individuals are twice as likely to develop PTSD than males.
Huggins acknowledged that sociodemographic factors, such as a higher risk of interpersonal violence or sexual assault that relate to PTSD symptoms, could explain that disparity. But according to Huggins, those gender differences don’t fully explain the disparity, which suggests there might be a reason related to biological sex.
According to Huggins, there are still some gaps in understanding PTSD, such as why some individuals recover from traumatic events and others live with lifelong stress and fear. While trauma is the immediate distress following an event, PTSD — recognized as a mental health disorder — involves intrusive and persistent symptoms.
Huggins explained that PTSD is far less common than experiencing trauma. “I think if we can know who’s the most at risk of PTSD biologically, we can be faster at preventing PTSD from manifesting after someone experiences trauma,” Huggins said. “It’s important that we can improve the lives of a lot of individuals who suffer from the disorder.”
“PTSD is kind of unique in that the better you understand the disorder, the more opportunity you have to prevent it from manifesting after a trauma occurs,” Huggins said. “You can’t prevent trauma, but you can have a lot of potential to intervene and help people reach better outcomes after they have that exposure.”
Huggins’ study focuses on a process known as fear generalization — how the brain learns fear from one experience and transfers that fear to other, similar stimuli. Clinically, according to Huggins, PTSD is associated with an overgeneralization of fear, meaning everyday experiences can trigger responses similar to those caused by trauma.
Huggins explained that previous non-human based studies suggest that estrogen may influence the brain regions involved in fear and emotion regulation, and that these effects can fluctuate throughout the menstrual cycle or decline sharply after menopause.
That’s why Huggins’ lab enrolls both younger females and older, post-menopausal females to explore how hormonal changes across the lifespan affect fear learning. Through comparison to post-menopausal females, researchers can examine brain activity patterns during periods of high versus low estrogen levels.
Participants enrolled in the study undergo functional MRI scans, self-reported questionnaires and provide saliva samples that measure hormone levels, stress markers like cortisol and inflammatory indicators.
“I do really prioritize research that employs multiple modalities because you get a richer picture of what’s going on with an individual,” Huggins said. “Even though we can look at the brain, looking at the self-report of psychological factors is always important to understand what someone actually feels or what they think.”
According to Huggins, the saliva samples in particular act as a snapshot of someone’s hormonal status. While the study is not longitudinal — meaning it doesn’t look at participants over a series of time — it does track where a participant is in their menstrual cycle during their time of data collection.
Although it’s too early to develop findings, Huggins explained that early analyses show notable differences in brain activation patterns between younger and older participants. This suggests that hormonal shifts could influence how the brain encodes and responds to fear.
Huggins explained that older adults are underrepresented in neuroimaging studies, so she’s excited to see data on these differences.
“If we know the parts of the brain that are going to be implicated in the potential development or maintenance of PTSD, that gives us a place to start, so that we can potentially have better treatments,” Huggins said.
Graduate students Jamie Terner and Katie Barlis from the Clinical Psychology Program at the UA help lead participant sessions, data analysis and MRI imaging for the study.
“It’s important to understand fear learning in the brain because fear is a universal human emotion, so to be able to have deeper insight and a better understanding of something that just about everyone experiences is always going to be impactful,” Terner said. “It is a core process implicated in individuals suffering from PTSD, so our work will hopefully serve important translational work, too.”
According to Terner, the gaps that this study addresses make it especially unique among other studies on fear learning or PTSD — particularly through comparing fear learning processes in young adults versus older adults, and having an entirely biologically-female sample.
For Barlis, the study represents a step toward connecting basic neuroscience research to real-world applications. Barlis explained that hormonal changes can influence attention, memory and other cognitive functions, but researchers still don’t understand how those changes affect daily life.
“Even though the fear-learning task is the same for everyone, participants seem to differ in how they experience the task,” Barlis said. “It’s a good reminder that individual differences, which may be shaped by a range of psychological and biological factors, make each person’s experience unique.”
Ultimately, Barlis hopes this work will lead to more personalized approaches to treatment and prevention. “By identifying specific biological and psychological processes linked to fear overgeneralization, we can tailor treatments more precisely,” Barlis said.
Huggins explained that the long-term goal of this research is to not only understand how fear works in the brain, but to use that knowledge to guide new interventions for trauma survivors.
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