Strong relationships in adulthood won't 'fix' effects of early childhood adversity
August 3, 2020
Science Daily/University of Notre Dame
Harsh conditions in early life are a fundamental cause of adult stress, and according to new research from the University of Notre Dame on wild baboons, this effect is not explained by a lack of social support in adulthood. The study is the first to present a comprehensive analysis of relationships between early life experiences, adult social bonds and adult stress responses within a single biological system.
Published in the Proceedings of the National Academy of Sciences, the research sheds light on the long-term effects of experiences such as famine, abuse, neglect or the death of a parent in early childhood. The researchers argue that dysregulated stress responses caused by those experiences -- including elevated stress hormones -- take a physiological toll on the body, and remain unaffected by healthy, supportive relationships in adulthood.
"Scientists have long believed that the link between early life adversity and adult stress could be due to a lack of social support in adulthood," said Elizabeth Archie, associate professor in the Department of Biological Sciences at Notre Dame and co-author of the study. "But what we've found through this study is that long-term effects of childhood hardships are more powerful than the near-term effects of social support -- even if those experiences took place many years in the past. The effects of early adversity and social support on stress appear to travel along independent physiological paths -- so 'fixing' one won't necessarily fix the other."
One of the challenges to fully understanding how early childhood adversity can manifest in adulthood is that it requires measuring and tracking experiences from birth over the course of several decades.
Archie's team analyzed data collected from 192 female baboons who were studied from birth through the Amboseli Baboon Research Project, an ongoing longitudinal effort that has been conducting research on the behavior of wild baboons in Kenya for almost 50 years. The animals are close evolutionary relatives to humans, and on average, they share a genetic similarity of 94 percent. Like many primates, baboons are highly social. They live in groups of around 20 to 150 animals, including several adult females, adult males and many offspring.
For the study, researchers measured life experience against levels of glucocorticoids (fGCs) -- hormones that regulate physiological functions such as metabolism and immune function, and moderate the body's response to stress.
"Dysregulations in stress hormones or stress response are major risk factors for depression, anxiety, chronic inflammation and other health problems, so the experience of early life adversity is thought to contribute to global health disparities," said Archie, who also serves as associate director of the Amboseli project.
Levels of fGCs in subjects who experienced three or more forms of childhood adversity were 9 percent higher than in those who experienced no hardships. Those who experienced two or more types of adversity showed fGC levels 14 percent higher than in peers who had endured only one form of hardship, and 21 percent higher than in peers who had experienced no hardship at all.
While previous research has shown experiencing hardships in childhood can make it harder to form strong, supportive relationships as adults, the Notre Dame study found that even when social bonds were developed in adulthood, it had a minor effect on fGC levels and physiological responses to stress.
"Social bonds can have a significant effect on adult health, stress and survival," Archie said, "but they cannot make up for the effects of early life adversity -- which means targeting early life adversity itself is crucial for improving adult health."
https://www.sciencedaily.com/releases/2020/08/200803184154.htm
What and how much we eat might change our internal clocks and hormone responses
November 8, 2019
Science Daily/Helmholtz Zentrum München - German Research Center for Environmental Health
For the first time, a study shows how glucocorticoid hormones, such as cortisol, control sugar and fat levels differently during day and night, feeding and fasting, rest and activity, over the course of 24 hours.
The research conducted in mice found that the time-of-day dependent metabolic cycle is altered by high caloric diet. Since glucocorticoids are widely used drugs for the treatment of inflammatory diseases, these findings published in Molecular Cell suggest that lean and obese patients might respond differently to steroid therapy. Finally, it reveals the biological function of daily rhythms of hormone secretion (high before awakening and feeding, low when sleeping and fasting) as well as daily cycles of sugar and fat storage or release by the liver.
Each cell in the human body is driven by an internal clock which follows the circadian rhythm of 24 hours. It is synchronized with the natural cycle of day and night mainly by sunlight, but also through social habits. In a healthy system, glucocorticoid stress hormones, are produced every morning by the adrenal gland. The secretion of glucocorticoidpeaks before awakening, prompting the body to use fatty acids and sugar as sources of energy, and enabling us to start our daily activities. When the circadian rhythm is disrupted (e.g. through shift work or jetlag) and/or when the glucocorticoid level alters (e.g. through Cushing syndrome or long-term clinical application), profound metabolic dysregulation can be caused -- like obesity, type 2 diabetes, and fatty liver disease. The researcher's goal therefore was to understand the relevance of these daily peaks of stress hormone secretion, the impact of these hormones on our "internal clock" and their role for daily cycles of metabolism.
Glucocorticoids' metabolic actions in the liver
To study glucocorticoids' metabolic actions in the liver, the researchers characterized the activity of their receptor, called the glucocorticoid receptor, using novel high throughput techniques. They analyzed mouse livers every 4 hours during day and night. The mice were either in normal condition or fed with high-fat diet. They then used cutting-edge technologies in genomics, proteomics, and bioinformatics to picture when and where the glucocorticoid receptor exerts its metabolic effects. The researchers dissected the impact of daily surges of glucocorticoid release in the 24-hour-cycle of liver metabolism. They could illustrate how glucocorticoids regulate metabolism differently during fasting (when the mice sleep) and during feeding (when they are active), by time-dependent binding to the genome. Furthermore, they showed how the majority of rhythmic gene activity is controlled by these hormones. When this control is lost (in so-called knockout mice), blood levels of sugar and fat are affected. This explains how the liver controls blood levels of sugar and fat differently during day and night.
In a next step, as the glucocorticoid receptor is a widely-used drug target in immune therapies, they investigated its genomics effects after the injection of the drug dexamethasone, a synthetic glucocorticoid that also activates this receptor. "With this experiment," explains Dr. Fabiana Quagliarini, "we found that the drug response was different in obese mice compared to lean mice. It is the first time to show that diet can change hormonal and drug responses of metabolic tissues."
New insights for Chronomedicine and metabolic disease therapy
Glucocorticoids are a group of natural and synthetic steroid hormones such as cortisol. They have potent anti-inflammatory and immunosuppressive properties which can control the activity of the immune system. This is why they are widely exploited in medicine. The major drawback is that glucocorticoids also cause severe side effects by virtue of their ability to modulate sugar and fat metabolism: Patients may develop obesity, hypertriglyceridemia, fatty liver, hypertension or type 2 diabetes.
"Understanding how glucocorticoids control 24-hour-cycles of gene activity in the liver and consequently blood levels of sugar and fat, provides new insights into 'Chronomedicine' and the development of metabolic disease. We could describe a new link between lifestyle, hormones and physiology at the molecular level, suggesting that obese people may respond differently to daily hormone secretion or to glucocorticoid drugs. These mechanisms are the basis for the design of future therapeutic approaches," highlights Prof. Henriette Uhlenhaut.
https://www.sciencedaily.com/releases/2019/11/191108171637.htm