Gender Matters When Times Get Tough
Louis Zamperini was a 23 year old Olympic runner when he enlisted in the US Air Force in 1941. His plane was shot down over the Pacific in 1943, forcing him to spend 47 days on a raft drifting southwest, only to spend the next two years in Japanese war camps enduring torture and hardship daily. Unlike most of his prison comrades, he survived to tell his tale—read Unbroken: A World War II Story of Survival, Resilience, and Redemption (2014) by Laura Hillenbrand. Zamperini died at 97, now an icon of resilience.
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Most soldiers don’t do so well under those demands. Yet it has been our custom to ask young men, and now women, in late adolescence to serve in combat situations that expose some of them to such hardships for months or years, with unpredictable consequences for their health. Given the size of the Veterans Administration’s health service, we might assume that our government knows what the health consequences across the lifespan are for people who have been repeatedly exposed to trauma, but that’s a hard and expensive question to answer.
The Vietnam-Era Twin Registry offers a start at addressing some of these kinds of questions. But this registry includes no women. And the lifespans of humans are long and messy and hard to study.
So about six years ago, while wondering about how childhood adversity turns into risks for heart disease and diabetes thirty years later, I found a group of researchers in my own department who were interested in asking similar questions of Sprague-Dawley rats, who pack a lifespan into about two years—a big advantage when asking about effects across the lifespan. Brent Myers, PhD, and I applied for a small grant that supports the translation of findings in basic science (often rats) into useful clinical approaches in humans. I served as the clinician on this team, and last week we published our first paper based on this project.
We designed a study that approximated putting 60 late adolescent rats, both males and females, through an experience similar to what Louis Zamperini went through. Our experimental groups suddenly found themselves exposed twice a day to a random series of tough events: being restrained in a plastic tube for 30 minutes, being shaken at 100 reps a minute for an hour, forced lying in damp bedding for an hour, sitting in the cold (38 degrees Fahrenheit) for an hour, breathing low oxygen air for 30 minutes, sleeping with a stranger, or spending the night alone. And this went on for 20 days, which is like five human years in a war camp. Then we let the rats resume their routines undisturbed until old age (15 months), when we sacrificed them and their luckier comparison groups, who had never endured what we called “chronic variable stress.”
This study carved new ground in two ways. First, it followed the rats for most of their lives, much longer than most stress studies, which only measure the immediate or early effects of stress exposures. Second, this study included females, who often have been excluded from rat research because their estrous cycle complicates some common physiologic measurements. We included females because we wanted to know if they respond to stress differently than males. Some of the wide variation in how humans respond to stress may be driven by gender. How much and what kinds of differences?
We found that the female Sprague-Dawley rats responded to the chronic variable stress with a different coping style (dubbed “passive”) and more rapid reactions with higher amounts of the stress hormone corticosterone than their male counterparts. And in old age the females still showed more rapid stress responses than the old guys. However, the females had more trouble with glucose tolerance over the years, suggesting that they may have been more at risk for metabolic disorders, like diabetes. We concluded that these animal data suggest the possibility that human females may react differently from males to chronic stress in adolescence. And maybe we should consider treating girls and women differently from boys and men, paying close attention to their coping styles, their stress hormone levels, and their glucose tolerance.
This study moves us another few inches closer to understanding the marvels of human variation in how we cope with adversity. We have been reminded that gender counts when times get tough, and women respond differently than men. Is this also true in children exposed to trauma at younger ages? As brutal as our chronic variable stress condition may seem for these rats, it may not match the duration or severity of the exposures of children who spend most of their formative years living in unsafe settings that deliver threats and trauma in random fashion on a daily basis. So much to learn about stress and resilience.