Stress in childhood and adulthood have combined impact on hormones and health

April 3, 2019

Science Daily/Association for Psychological Science

Adults who report high levels of stress and who also had stressful childhoods are most likely to show hormone patterns associated with negative health outcomes, according to findings published in Psychological Science, a journal of the Association for Psychological Science.

One of the ways that our brain responds to daily stressors is by releasing a hormone called cortisol -- typically, our cortisol levels peak in the morning and gradually decline throughout the day. But sometimes this system can become dysregulated, resulting in a flatter cortisol pattern that is associated with negative health outcomes.

"What we find is that the amount of a person's exposure to early life stress plays an important role in the development of unhealthy patterns of cortisol release. However, this is only true if individuals also are experiencing higher levels of current stress, indicating that the combination of higher early life stress and higher current life stress leads to the most unhealthy cortisol profiles," says psychological scientist Ethan Young, a researcher at the University of Minnesota.

For the study, Young and colleagues examined data from 90 individuals who were part of a high-risk birth cohort participating in the Minnesota Longitudinal Study of Risk and Adaptation.

The researchers specifically wanted to understand how stressful events affect the brain's stress-response system later in life. Is it the total amount of stress experienced across the lifespan that matters? Or does exposure to stress during sensitive periods of development, specifically in early childhood, have the biggest impact?

Young and colleagues wanted to investigate a third possibility: Early childhood stress makes our stress-response system more sensitive to stressors that emerge later in life.

The researchers assessed data from the Life Events Schedule (LES), which surveys individuals' stressful life events, including financial trouble, relationship problems, and physical danger and mortality. Trained coders rate the level of disruption of each event on a scale from 0 to 3 to create an overall score for that measurement period. The participants' mothers completed the interview when the participants were 12, 18, 30, 42, 48, 54, and 64 months old; when they were in Grades 1, 2, 3, and 6; and when they were 16 and 17 years old. The participants completed the LES themselves when they were 23, 26, 28, 32, 34, and 37 years old.

The researchers grouped participants' LES scores into specific periods: early childhood (1-5 years), middle childhood (Grades 1-6), adolescence (16 and 17 years), early adulthood (23-34 years), and current (37 years).

At age 37, the participants also provided daily cortisol data over a 2-day period. They collected a saliva sample immediately when they woke up and again 30 minutes and 1 hour later; they also took samples in the afternoon and before going to bed. They sent the saliva samples to a lab for cortisol-level testing.

The researchers found that neither total life stress nor early childhood stress predicted cortisol level patterns at age 37. Rather, cortisol patterns depended on both early childhood stress and stress at age 37. Participants who experienced relatively low levels of stress in early childhood showed relatively similar cortisol patterns regardless of their stress level in adulthood. On the other hand, participants who had been exposed to relatively high levels of early childhood stress showed flatter daily cortisol patterns, but only if they also reported high levels of stress as adults.

The researchers also investigated whether life stress in middle childhood, adolescence, and early adulthood were associated with adult cortisol patterns, and found no meaningful relationships.

These findings suggest that early childhood may be a particularly sensitive time in which stressful life events -- such as those related to trauma or poverty -- can calibrate the brain's stress-response system, with health consequences that last into adulthood.

Young and colleagues note that cortisol is one part of the human stress-response system, and they hope to investigate how other components, such as the microbiome in our gut, also play a role in long-term health outcomes.

https://www.sciencedaily.com/releases/2019/04/190403080454.htm

Modeling the microbiome

Physicists develop new mathematical approaches to analyze interactions between gut bacteria

December 5, 2018

Science Daily/University of California - Santa Barbara

The gut microbiome -- the world of microbes that inhabit the human intestinal tract -- has captured the interest of scientists and clinicians for its critical role in health. However, parsing which of those microbes are responsible for effects on our wellbeing remains a mystery.

Taking us one step closer to solving this puzzle, UC Santa Barbara physicists Eric Jones and Jean Carlson have developed a mathematical approach to analyze and model interactions between gut bacteria in fruit flies. This method could lead to a more sophisticated understanding of the complex interactions between human gut microbes.

Their finding appear in the Proceedings of the National Academy of Sciences.

"Especially over the past 20 years or so, scientists have been finding that the microbiome interacts with the rest of your body, with your immune system, with your brain," said Jones, a graduate student researcher in Carlson's lab. "Many diseases are associated with certain microbial compositions in the gut."

The human gut microbiome as yet is too diverse to fully analyze. Instead, the research team, led by Carnegie Institution for Science biologist Will Ludington, used the fruit fly as a model organism to tease apart how the presence of particular gut bacteria could lead to physical and behavioral effects in the host organism.

In their paper, "Microbiome interactions shape host fitness," Carlson, Jones, Ludington and colleagues examine the interactions between five core species of bacteria found in the fly gut, and calculate how the presence or absence of individual species influences aspects of the fly's fitness, including lifespan, fertility and development. "The classic way we think about bacterial species is in a black-and-white context as agents of disease -- either you have it or you don't," Ludington said. "Our work shows that isn't the case for the microbiome. The effects of a particular species depend on the context of which other species are also present."

Building on previous research that found the presence versus the absence of bacteria affected the longevity of an organism (sterile hosts lived longer), the researchers' work on this project revealed that the situation is far more nuanced. For example, the presence of certain bacteria might increase the host's fecundity, while others might decrease longevity. "As we examined the total of what we call a fly's fitness -- it's chances of surviving and creating offspring -- we found that there was a tradeoff between having a short lifespan with lots of offspring, versus having a long lifespan with few offspring," Ludington explained. "This tradeoff was mediated by microbiome interactions."

To decipher these interactions, Ludington performed a combinatorial assay, rearing 32 batches of flies each inhabited by a unique combination of the five bacteria. For each bacterial combination, Ludington measured the fly's development, fecundity and longevity. The analysis of the interactions required Carlson and Jones to develop new mathematical approaches.

"One model that often would be a starting point would be to consider the interactions between pairs of bacteria," said Carlson, whose research delves into the physics of complex systems. "This research shows us that a strictly pairwise model does not capture all of the observed fly traits."

What the study shows, the researchers said, is that the interactions between the bacterial populations are as significant to the host's overall fitness as their presence -- the microbiome's influence cannot be solely attributed to the presence or absence of individual species. "In a sense," said Jones, "the microbiome's influence on the host is more than the sum of its parts."

The newly developed models could be extended to better understand the interactions of the thousands of different species of bacteria in the human microbiome, which could, in turn, shed light on the many connections to microbiome-affiliated diseases including mood disorders, neurological dysfunctions, autoimmune diseases and antibiotic-resistant superbugs.

"In many cases infections are caused by bacteria that we all have in ourselves all the time, and are kept in check by native gut bacteria," Carlson said. It's not so much that the infection is some new, horrible bacteria, she explained, but that the populations of other bacteria have changed, resulting in unrestricted growth for the infectious bacteria.

"It's really about understanding the population dynamics of these systems," she said.

https://www.sciencedaily.com/releases/2018/12/181205152208.htm