Monthly Archives: October 2019

PTSD: The Unknown Truth About the Sexes
Touré Jones
Junior, human health major
Emory University

My Research Project

Post-traumatic stress disorder (PTSD) is a debilitating mental illness that heavily impacts an individual’s physical, mental and emotional health. One overlooked, but very important, consequence of this illness is that individuals with PTSD have an increased risk of developing hypertension and cardiovascular disease1. Past research has revealed that those with PTSD have an exaggerated blood pressure and heart rate response and a blunted heart rate variability response to acute mental stress1. While these studies have improved our understanding of PTSD and the physiological effects it has, they don’t highlight a very important factor: the possibility that it affects men and women differently.

PTSD studies have typically been either all men, or a very few women included in a mostly male population. The research has produced results that primarily focus on male reactivity2, andhas neglected an entire demographic of PTSD victims that seem to have a different response. While men and women have a similar rate of experiencing traumatic events, women are twice as likely to be diagnosed with PTSD3. In addition, healthy premenopausal women have a lower risk of developing cardiovascular disease compared to men, although once diagnosed with PTSD, this risk increases three times, placing the women at higher risk3. Given these biological differences, the purpose of this study was to determine if there is also a sex difference in autonomic and cardiovascular responses to acute mental stress in individuals who have PTSD.

Our study consisted of 33 individuals— 15 women and 18 men—for a total of two visits. The first visit was a screening where we took the volunteers’ vital signs, gave them PTSD surveys to determine the severity of their condition and checked for exclusion criteria to ensure they could be in the study. The second visit was a micro visit, where we recorded experimental data. We measured the study subjects’ blood pressure, heart rate and muscle sympathetic nerve activity at baseline, then those same recordings during three minutes of mental stress. Beat-to- beat blood pressure was recorded using a continuous noninvasive arterial pressure (CNAP) monitor and heart rate was recorded via an electrocardiogram (EKG). Muscle sympathetic nerve activity (MSNA) was recorded via the microneurography procedure. Mental arithmetic served as our mental stressor: the participants subtracted a given number from a numbered index card continuously for three minutes while a “coach” was pressuring them to give an answer as quickly as possible. 

At baseline, measurements for age, body mass index, clinician-administered PTSD scale (CAPS) and PSTD checklist–military version (PCLM) survey scores, blood pressure and heart rate variability were all comparable between the sexes. However, MSNA was significantly different. This was a very interesting find, as we were not anticipating this result. In healthy populations, men have a higher MSNA at rest than women. Based on this data, it seems that women with PTSD have a higher resting MSNA than men. In response to mental stress, systolic arterial pressure was higher in women than men, while diastolic arterial pressure was comparable between the two groups. In addition, heart rate seemed to be higher in women than men, but had not reached significance, although MSNA in response to mental stress was significantly higher in women compared to men. Even more interesting was the root mean square of the successive differences (RMSSD), the time domain measurement of parasympathetic nervous system activity, was comparable between both groups, but the high frequency domain for parasympathetic response showed women having a decreased response to mental stress than men.

In conclusion, resting MSNA was significantly higher in the women than the men. Systolic arterial pressure reactivity to mental arithmetic as higher in women with PTSD compared to men, while diastolic arterial pressure reactivity was comparable between the groups. Heart rate was comparable between women and men with PTSD. MSNA reactivity to mental stress was higher in women than men while heart failure response was blunted in women compared to men suggesting greater dysregulation of the autonomic nervous system in women with PTSD. RMSSD was comparable between men and women in response to mental stress.

In summary, women with PTSD in our study have an increased blood pressure and sympathetic response in addition to a blunted parasympathetic response to acute mental stress. These results provide insight into the mechanisms that are associated with a higher risk of cardiovascular disease in women with PTSD.

Realities of Research

Doing research in a lab was very different from my high school research experiences. For one, this was a clinical lab, so I was working with people every day, which was a rewarding experience. Also, my lab team was made up of very intelligent, cohesive and welcoming individuals, so during every study I was able to learn something new while having a good time. I also had to learn how to set up the lab for the studies we would be conducting, so I had to understand the procedure being performed and how to prepare for it. For example, one procedure we performed was microneurography— a qualified lab member inserted a tungsten electrode into the participants’ peroneal nerve to record sympathetic activity. 

What surprised me about the experience was how often research doesn’t go as planned, especially when working with people. Some study participants wouldn’t come in to the lab as scheduled, or if they did, they didn’t want to go forward with certain procedures for a variety of reasons. Because of this, some patients didn’t have all of the data I anticipated collecting, but that was just a part of the research process.

As for our results, it was very rewarding to see my hard time and effort come to fruition. Some of the results I expected, but others I wasn’t expecting at all. Honestly, each result made the experience all the more exciting.

Life as a Scientist

Life this summer was challenging, but rewarding. I experience many exciting things that have provided me with good memories. The feeling that I felt once I formed graphs based on my data was great and was the best part of the experience; it was the result of my hard work and dedication to my project.

The worst part of the experience would have to be the hours I spent trying to understand certain topics by myself. While learning more about what I am doing interested me, there was some information I needed to know but took me a little while to grasp, which often annoyed me. However, once I did understand it, the passion I had for my project increased. Finally, my lab team was instrumental in me developing this project, especially my mentor. Her mentorship has taught me so much during the weeks I spent with her this summer and I am excited to learn even more.

References:

    1. Edmondson D, von Kanel R. Post-traumatic stress disorder and cardiovascular disease. The Lancet Psychiatry 2017;4:320-9.
    2. Park, J., Marvar, P. J., Liao, P., et al. (2017). Baroreflex dysfunction and augmented sympathetic nerve responses during mental stress in veterans with post-traumatic stress disorder. The Journal of Physiology, 595(14), 4893–4908. doi:10.1113/JP274269
    3. Kubzansky LD, Koenen KC, Jones C, Eaton WW. A prospective study of posttraumatic stress disorder symptoms and coronary heart disease in women. Health psychology : Official Journal of the Division of Health Psychology, American Psychological Association 2009;28:125-30.

Touré Jones is a junior majoring in human health at Emory University in Atlanta. He is a 2019 Short-Term Research Education Program to Increase Diversity in Health-Related Research (STRIDE) Fellow working in Dr. Jeanie Park’s lab also at Emory University. Touré’s fellowship is funded by APS and a grant from the National Heart, Lung, and Blood Institute (Grant #1: R25 HL115473-01). After graduation, Touré plans on attending medical school to pursue his dreams of being a physician.

Some Serious Monkey Business
Lucas Barrett
Senior, biology major
University of Kentucky

My Research Project

My research project was focused on using the African green monkey as a translational animal model for human disease. I was particularly interested in the gene that encodes for a protein known to be a component of cholesterol transport. The protein also has a natural ability to protect against certain parasites. In humans, two different versions of this gene have been associated with early-onset kidney disease. Our lab found a version of this gene in the African green monkey that is associated with high blood pressure, and I continued this discovery by looking for additional monkey species that have a similar version of the gene.

In order to find more monkeys with the insertion, I took tissue samples from animals at our vivarium, from which I then extracted DNA.  I also followed the kidney function of monkeys with different variations of the gene to discover whether it was associated with kidney disease in the African green monkey. I assessed kidney function by measuring chemical levels from blood and urine samples which helped determine whether this gene was a marker for kidney disease in this animal model. The main goal of this summer’s project was to identify the African green monkey as a model to study this specific type of kidney disease in humans through the investigation of alternate versions of this gene.

Realities of Research

Doing research has been both the most rewarding and most frustrating endeavor that I have ever undertaken. Being engaged in new scientific discovery is exciting, but the time and effort that go into research can be exhausting. A particularly difficult part of research this summer was troubleshooting why an experiment or laboratory technique did not work as expected.

I was most surprised at how acceptable and common it is to be wrong. Amazingly, in the scientific community, there is nothing inherently bad about being wrong as long as you learn from and adapt to the information you uncover. Working as part of a team in the lab was one of the best parts of this experience. Being able to discuss different projects and rely on others for help as they rely on you was enjoyable, and pushed me to be an expert on my assigned tasks. At the same time, I learned to be competent and well-versed in the other tasks going on in the lab.

Life as a Scientist

Working and living as a scientist for the summer was an experience full of joy and fun, but I also learned a lot that I didn’t know about the day-to-day life conducting research. I was fortunate to go for three weeks to the island of Saint Kitts in the Caribbean islands to do field work that involved collecting data and samples for the lab.

Most people I told about this trip assumed that a stay in the Caribbean would be laid back and more akin to a vacation than a work trip, but nothing could have been further from reality. Out of the 20 days we were on the island, we only took one day completely off from work and I did not anticipate how tiring it would be to work outside in a tropical climate. Despite falling into bed most days from exhaustion, I learned more every day and was fascinated by working with our live animal model; instead of simply working with blood, urine and tissue in the lab.

Lucas Barrett is a senior majoring in biology at the University of Kentucky in Lexington. He is a 2019 Undergraduate Summer Research Fellow (UGSRF) working in the laboratory of Dr. Jeffrey Osborn at the University of Kentucky.  Lucas’ fellowship is funded by the American Physiological Society. After graduation, Lucas plans to pursue a career as a physician-scientist studying human disease. He plans to enroll in a medical scientist program after finishing his degree at the University of Kentucky.

PoWeRful mice and the effect of satellite cell depletion
Alec Dupont
Junior, biomedical science major
Auburn University

My Research Project

My project involved examining the adaptation of skeletal muscle to resistance exercise in mice that had been depleted of muscle stem cells (satellite cells). Generally, muscle growth is accompanied by an increase in protein synthesis and the differentiation of satellite cells into muscle nuclei. During this project, we examined if growth happens without the addition of satellite cells into muscle. As certain clinical populations have reduced satellite cell content and muscle mass, our project aimed to provide insights into how muscles respond to a growth stimulus with the loss of this cell population.

We used Progressive Weighted Wheel running (PoWeR) as a model for resistance exercise. PoWeR involves voluntary running activity of the mice in weighted running wheels. The weight placed on the running wheel is gradually increased over the course of four to eight weeks, overloading the musculature and causing a growth response called muscle hypertrophy. Using a genetic mouse model that allowed for the selective depletion of satellite cells, we compared sedentary- and resistance-exercised mice in groups of satellite cell-replete (vehicle treated) and -depleted (tamoxifen treated) mice. We compared muscle hypertrophy and other physiological adaptations between groups to determine the effects of satellite cell depletion. At the completion of this project, we hoped to gain a further understanding of the role satellite cells play in muscle growth.

Realities of Research

My main focus for the summer was using muscle tissue from the PoWeR mice, and making it possible to obtain data and useful information. I accomplished this through immunohistochemistry, a laboratory technique where we cut cross sections of the muscle and stain them for proteins of interest. This staining allowed us to visualize the sections under the microscope, image them and quantify the images using different forms of software. This technique presented certain challenges because the tissue must be carefully prepared and stored to prevent degradation. Poor quality tissue introduced variability outside of what is normal to the mice models. For example, having to overcome challenges and work to optimize a stain meant visualizing newly formed RNA in muscle nuclei. The stain can appear too dull and the quality would not be high enough to draw conclusions unless the procedure was optimized. Overcoming these challenges provided stunning images and reliable data. We found that although satellite cells were not absolutely required for muscle growth in response to weighted wheel running, there was a decrease in growth in the satellite cell depleted mice.

Life as a Scientist

The day-to-day life of a research scientist presented me with a constantly changing experience that was more engaging than the traditional classroom setting. There was always a new aspect of the project to investigate. It was incredibly satisfying to see your work come together in data that tell a cohesive story. The process of getting there was occasionally tedious though. For example, we’d normalize our data to the number of fibers in the muscle cross section and when the software couldn’t count for us, we were forced to count by hand. When the sections were between 600 and 800 fibers in a study with 48 mice, that part of research tended to drag. But that was only a minor inconvenience to a necessary bump in the road towards a satisfying research project.

Alec Dupont is a junior at Auburn University in Auburn, Alabama, studying biomedical science. He is a 2019 Undergraduate Summer Research Fellow (UGSRF) working under Dr. Charlotte Peterson at the Center for Muscle Biology at the University of Kentucky in Lexington. Alec’s work is funded by the American Physiological Society’s UGSRF program and a grant from the National Institute of Health to Dr. Charlotte Peterson and Dr. John McCarthy (AR060701).