Stress in small children separated from their parents may alter genes

February 18, 2020

Science Daily/SAGE

Several studies show that small children cared for outside the home, especially in poor quality care and for 30 or more hours per week, have higher levels of cortisol than children at home.

Experts in the emotional needs of small children say increased levels of the stress hormone cortisol in babies and small children who are separated from their parents, especially their mothers, could have a long-term genetic impact on future generations. In a commentary published by the Journal of the Royal Society of Medicine, the authors say that several studies show that small children cared for outside the home, especially in poor quality care and for 30 or more hours per week, have higher levels of cortisol than children at home.

Professor Sir Denis Pereira Gray, Emeritus Professor of General Practice at the University of Exeter, and President of the children's charity 'What About the Children?' who wrote the paper with two colleagues, said: "Cortisol release is a normal response to stress in mammals facing an emergency and is usually useful. However, sustained cortisol release over hours or days can be harmful."

The authors say that raised cortisol levels are a sign of stress and that the time children spend with their parents is biologically more important than is often realised. Stress has been associated with children, particularly boys, acting aggressively. Not all children are affected, but an important minority are. Raised cortisol levels are associated with reduced antibody levels and changes in those parts of the brain which are associated with emotional stability.

"Environmental factors interact with genes, so that genes can be altered, and once altered by adverse childhood experiences, can pass to future generations. Such epigenetic effects need urgent study," say the authors.

Sir Denis added: "Future research should explore the links between the care of small children in different settings, their cortisol levels, DNA, and behaviour."

https://www.sciencedaily.com/releases/2020/02/200218131850.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

Stress reduction benefits from petting dogs, cats

July 15, 2019

Science Daily/Washington State University

Just 10 minutes of interacting with cats and dogs produced a significant reduction in students' cortisol, a major stress hormone.

College is stressful. Students have classes, papers, and exams. But they also often have work, bills to pay, and so many other pressures common in modern life.

Many universities have instituted "Pet Your Stress Away" programs, where students can come in and interact with cats and/or dogs to help alleviate some of the strain.

Scientists at Washington State University have recently demonstrated that, in addition to improving students' moods, these programs can actually get "under the skin" and have stress-relieving physiological benefits.

"Just 10 minutes can have a significant impact," said Patricia Pendry, an associate professor in WSU's Department of Human Development. "Students in our study that interacted with cats and dogs had a significant reduction in cortisol, a major stress hormone."

Pendry published these findings with WSU graduate student Jaymie Vandagriff last month in AERA Open, an open access journal published by the American Educational Research Association.

This is the first study that has demonstrated reductions in students' cortisol levels during a real-life intervention rather than in a laboratory setting.

The study involved 249 college students randomly divided into four groups. The first group received hands-on interaction in small groups with cats and dogs for 10 minutes. They could pet, play with, and generally hang out with the animals as they wanted.

To compare effects of different exposures to animals, the second group observed other people petting animals while they waited in line for their turn. The third group watched a slideshow of the same animals available during the intervention, while the fourth group was "waitlisted."

Those students waited for their turn quietly for 10 minutes without their phones, reading materials, or other stimuli, but were told they would experience animal interaction soon.

Several salivary cortisol samples were collected from each participant, starting in the morning when they woke up. Once all the data was crunched from the various samples, the students who interacted directly with the pets showed significantly less cortisol in their saliva after the interaction. These results were found even while considering that some students may have had very high or low levels to begin with.

"We already knew that students enjoy interacting with animals, and that it helps them experience more positive emotions," Pendry said. "What we wanted to learn was whether this exposure would help students reduce their stress in a less subjective way. And it did, which is exciting because the reduction of stress hormones may, over time, have significant benefits for physical and mental health."

Now Pendry and her team are continuing this work by examining the impact of a four-week-long animal-assisted stress prevention program. Preliminary results are very positive, with a follow-up study showing that the findings of the recently published work hold up.

https://www.sciencedaily.com/releases/2019/07/190715114302.htm

Obesity, risk of cognitive dysfunction? Consider high-intensity interval exercise

Study first to use high-intensity interval exercise on obese individuals to test effects on cognitive dysfunction

Science Daily/December 10, 2018

Florida Atlantic University

Researchers have discovered what might be an effective strategy to prevent and combat cognitive dysfunction in obese individuals. They are the first to examine the modulatory role of an exercise-induced protein in the brain that promotes neuron survival and used high-intensity interval exercise (HIIE) in obese and normal-weight subjects. Obesity reduces the expression of this protein and lower levels are associated with Alzheimer's, Parkinson's and obesity. HIIE upregulated this protein in the obese subjects compared to normal-weight subjects.

It's fast-paced, takes less time to do, and burns a lot of calories. High-intensity interval exercise is widely recognized as the most time-efficient and effective way to exercise. In a first-of-its-kind study, researchers from Florida Atlantic University have discovered another important health benefit of these short bursts of intense exercise with rest intervals. It could also be an effective strategy to prevent and combat cognitive dysfunction in obese individuals.

Obesity reduces the expression of brain-derived neurotrophic factor (BDNF), a protein in the brain that promotes the survival of nerve cells or neurons. Lower levels of this protein are associated with Alzheimer's disease, Parkinson's disease, and obesity. Although studies have shown that obesity is a risk factor for cognitive dysfunction, the mechanisms of this relationship are not fully understood.

To-date, studies on exercise and BDNF response in obese populations have only used continuous moderate-intensity exercise without rest intervals. FAU researchers and collaborators from the University of Texas at Austin and Purdue University, are the first to examine the modulatory role of obesity on exercise-induced BDNF release and to use an acute high-intensity interval exercise protocol as a practical model to measure the phenomena of BDNF release in both obese and normal-weight subjects. They also examined the potential relationship of exercise-induced BDNF with blood lactate and cortisol.

Results of study, published in the journal Experimental Biology and Medicine, show that the BDNF response to acute high-intensity interval exercise was greater than continuous moderate-intensity exercise in obese subjects when compared to normal-weight subjects. Similarly, although acute high-intensity interval exercise induced greater blood lactate and plasma cortisol levels than continuous moderate-intensity exercise, obese subjects produced less blood lactate, but showed no difference in cortisol than normal-weight subjects.

These findings suggest that acute high-intensity interval exercise may be a more effective protocol to upregulate BDNF expression in an obese population, independent of increased lactate and cortisol levels.

"High-intensity interval exercise is a time-efficient strategy with similar or superior physiological benefits that promotes the expression of a growth factor typically associated with brain health, yet that appears to be down regulated in obesity," said Chun-Jung (Phil) Huang, Ph.D., lead author and an associate professor in the Exercise Biochemistry Laboratory, Department of Exercise Science and Health Promotion, in FAU's College of Education. "The relative simplicity and efficacy of high-intensity interval exercise supports its use as a preventive measure and as an intervention to combat obesity and other chronic disease conditions."

For the study, male subjects participated in a counterbalanced and caloric equated experiment of high-intensity interval exercise. The high-intensity interval exercise protocol consisted of a five minute walking or jogging warm-up, followed by four high-intensity intervals lasting four minutes each, followed by three minutes of active recovery followed by each high-intensity interval. Blood samples were collected prior to, immediately following exercise, and an hour into recovery for measurements of serum BDNF, blood lactate, and plasma cortisol.

Other findings from the study show statistically significant differences between the obese and normal-weight groups for body weight, BMI, systolic and diastolic blood pressures, and waist/hip circumferences and ratio. In addition, both the obese and normal-weight groups had comparable heart rate responses during both exercise protocols, demonstrating a similar relative exercise intensity and effort between groups. Therefore, the BDNF response was likely not influenced by disparities between aerobic fitness, with a greater level in obese subjects than normal-weight subjects following acute high-intensity interval exercise vs. continuous moderate-intensity exercise.

"Increased levels of cortisol have been shown to down regulate BDNF expression, however, this relationship in response to exercise still remains equivocal," Huang. "Specifically, our study and others, did not observe any correlation between cortisol and BDNF following either acute high-intensity exercise or continuous moderate-intensity exercise protocol, yet, the report of such is opposite."

Aerobic training has been shown to not only provide beneficial anti-inflammatory and cardiovascular benefits, but also reductions in age-related cognitive decline. It also has been shown to preserve brain volume and potentially improve blood flow.

The Centers for Disease Control and Prevention estimates that about 93.3 million Americans were classified as obese in 2016. The annual medical costs of obesity were estimated at around $147 billion in 2008.

https://www.sciencedaily.com/releases/2018/12/181210091027.htm

Hair cortisol levels predict which mothers are more likely to suffer postpartum depression

November 13, 2017

Science Daily/University of Granada

Researchers from the University of Granada (UGR), who belong to the Brain, Mind and Behavior Research Center (CIMCYC, from its abbreviation in Spanish) and the Faculty of Psychology, have proven that cortisol levels (a steroid hormone secreted as a response to stress) present in the hair of pregnant women during the first or third trimesters of pregnancy may indicate which of them are more likely to suffer postpartum depression.

Their work, published in the PLoS ONE journal, showed that hair cortisol levels in women who developed postpartum depression were higher throughout pregnancy than those seen in women who hadn't developed it, being that difference statistically more significant during the first and third trimesters.

The UGR researchers carried out their study doing a follow-up on 44 pregnant women throughout the whole gestation period and after giving birth. Each trimester the mothers underwent a series of tests that evaluated their stress and psychopathological symptoms while simultaneously taking hair samples from which the researchers extracted the cortisol corresponding to the last three months.

The following days after labor the researchers evaluated the mothers' emotional state in order to assess who among them had developed postpartum depression.

Quarterly psychopathological symptoms

Additionally, the results of the study showed that the participants which developed postpartum depression showed higher levels of somatization during the first trimester. During the second trimester they showed higher levels of somatization, obsession-compulsion, depression and anxiety, and during the third trimester they showed higher levels of somatization and pregnancy-specific stress. Therefore, all those symptoms along with higher levels of cortisol would be indicators of a future postpartum depression.

As María Isabel Peralta Ramírez, lead researcher of the project says, the consequences of those results are very important in the prevention of postpartum depression, "since they show that there are various altered psychological and hormonal variables throughout the whole gestation period in comparison to those women who will not suffer postpartum depression. Detecting those differences is the key to anticipate the psychological state of the mother as well as the consequences for the baby that said state could mean."

This study belongs to the GESTASTRESS research project, in the research excellence framework of the Spanish Ministry of Economy and Competitiveness. Its primary goal has been to assess the effects of psychological stress on the mother throughout the whole gestation period as well as on birth variables, and on the baby's stress and neurodevelopment.

https://www.sciencedaily.com/releases/2017/11/171113111040.htm

Depression and chronic stress accelerates aging

November 10, 2011

Science Daily/Umeå University

People with recurrent depressions or those exposed to chronic stress exhibits shorter telomeres in white blood cells.

The telomere is the outermost part of the chromosome. With increasing age, telomeres shorten, and studies have shown that oxidative stress and inflammation accelerates this shortening. On this basis it has been suggested that telomere length is a measure of biological aging, and telomere length has subsequently been linked to age-related diseases, unhealthy lifestyle, and longevity.

The research team shows that shorter telomere length is associated with both recurrent depression and cortisol levels indicative of exposure to chronic stress.

"The test revealed that cortisol levels indicative of chronic stress stress are associated with shorter telomeres in both depressed and healthy individuals," says Mikael Wikgren, a doctoral candidate in the research group.

The fact that depressed patients as a group have shorter telomere lengths compared to healthy individuals can be largely explained by the fact that more depressed people than healthy people have disturbed cortisol regulation, which underscores that cortisol regulation and stress play a major role in depressive disorders.

http://www.sciencedaily.com/releases/2011/11/111109093729.htm