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Stress-related inflammation may increase risk for depression

Preexisting differences in the sensitivity of a key part of each individual’s immune system to stress confer a greater risk of developing stress-related depression or anxiety, according to a study conducted at the Icahn School of Medicine at Mount Sinai and published October 20 in the Proceedings of the National Academy of Sciences (PNAS).

depressionInflammation is the immune system’s response to infection or disease, and has long been linked to stress. Previous studies have found depression and anxiety to be associated with elevated blood levels of inflammatory molecules and white blood cells after a confirmed diagnosis, but it has been unclear whether greater inflammation was present prior to the onset of disease or whether it is functionally related to depression symptomology.

Specifically, the new study measured the cytokine IL-6 in non-aggressive mice prior to and after repeated social stress invoked by an aggressive mouse. They found that IL-6 levels were higher in mice that were more susceptible to stress than in “stress-resilient” mice. They also found the levels of leukocytes (white blood cells that release IL-6) were higher in stress susceptible mice before stress exposure. The researchers then validated the increased levels of IL-6 in two separate groups of human patients diagnosed with treatment-resistant Major Depressive Disorder.

The Mount Sinai study results revolve around the peripheral immune system, a set of biological structures and processes in the lymph nodes and other tissues that protect against disease. Inflammation is a culprit of many disease conditions when it happens in the wrong context or goes too far. Under normal conditions when the immune system perceives a threat (e.g. invading virus), inflammatory proteins called interleukins are released by white blood cells as an adaptive mechanism to limit injury or infection. However, in some instances, the immune system may become hyper responsive to an “insult,” leading to chronic dysregulation of inflammatory processes that ultimately cause disease.

“Our data suggests that pre-existing individual differences in the peripheral immune system predict and promote stress susceptibility,” says lead author Georgia Hodes, PhD, Postdoctoral Researcher in Neuroscience. “Additionally, we found that when mice were given bone marrow transplants of stem cells that produce leukocytes lacking IL-6 or when injected with antibodies that block IL-6 prior to stress exposure, the development of social avoidance was reduced compared with their respective control groups, demonstrating that the emotional response to stress can be generated or blocked in the periphery.”

Evidence in the current study is the first to suggest that Interleukin 6 response prior to social stress exposure can predict individual differences in vulnerability to a subsequent social stressor.

The research team, led by Scott Russo, PhD, Associate Professor of Neuroscience, exposed mice to two social stress models that are translational to social stressors experienced by humans. They measured blood levels of cytokines in non-aggressive mice before and after repeated social defeat stress invoked by exposure to an aggressive mouse for 10 minutes daily for 10 days or after 10 days of witnessing defeat of another mouse, a purely emotional stressor. The researchers classified the non-aggressive mice as susceptible based on a preference to spend more time near an empty cage rather than near a new mouse on a subsequent social interaction test, whereas resilient mice showed the opposite pattern. Interleukin-6 was the only cytokine significantly elevated in susceptible mice compared with unstressed and resilient mice.

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Want to improve long-term memory? This will help…

Think that improving your long term memory is all brain training and omega-3 supplements? Think again. A new study from researchers at Georgia Institute of Technology in Atlanta suggests that working out at the gym for as little as 20 minutes can improve long-term memory.

Memory exercisePrevious studies have shown that memory may be improved by several months of aerobic exercises, such as running, cycling or swimming. However, the findings of the new study – published in the journal Acta Psychologica – demonstrate that a similar memory boost can be achieved in a much shorter period.

Exercise protects against depression

A new study, published in the journal Cell, investigates the mechanisms behind the protection from stress-induced depression offered by physical exercise. 

Support for depression and mental healthExercise has well-known benefits against symptoms of depression.

Last year, an updated systematic review by UK researchers analyzed 35 randomized controlled trials on the subject involving a total of 1,356 participants diagnosed with depression.

The systematic review found that exercising was as beneficial for people with depression as psychological therapy or taking antidepressants. However, the researchers cautioned that higher quality studies are needed to confirm the results.

Scientists know that during exercise, there is an increase in skeletal muscle of a protein called PGC-1a1. The researchers behind the new study – from the Karolinska Institutet in Sweden – wanted to see whether this protein increase might be implicated in the protective benefits of exercise.

Genetically modified mice with high levels of PGC-1a1 in skeletal muscle (that showed many characteristics of well-trained muscles) were exposed – along with normal mice – to a stressful environment in the lab. This involved being exposed to loud noises, flashing nights and having their circadian rhythm reversed at irregular intervals.

After 5 weeks of being exposed to mild stress, the normal mice developed symptoms of depression, whereas the genetically modified mice displayed no depressive behavior.

“Our initial research hypothesis was that trained muscle would produce a substance with beneficial effects on the brain,” says Jorge Ruas, principal investigator at the Department of Physiology and Pharmacology, Karolinska Institutet.

Investigating the genetically modified mice further, the researchers made the discovery that – as well as the elevated levels of PGC-1a1 – the mice also had higher levels of KAT enzymes. These enzymes convert kynurenine – a substance formed during stress – into kynurenic acid. The exact function of this acid is not known, but patients with mental illness are known to have high levels of it.

Kynurenine conversion process ‘may be protective mechanism’

When normal mice were given kynurenine as part of the study, the researchers found that they exhibited symptoms of depression. However, when the elevated PGC-1a1 mice were given kynurenine, their behavior seemed unaffected.

The researchers also noticed that even when the PGC-1a1 mice were administered kynurenine, their blood did not show raised levels of kynurenine. This is because the KAT enzymes in the trained muscles of the PGC-1a1 mice were able to quickly convert it to kynurenic acid. The researchers think that this quick conversion process therefore, is a protective mechanism.

“In neurobiological terms, we actually still don’t know what depression is,” says Mia Lindskog, researcher at the Department of Neuroscience at Karolinska Institutet. “Our study represents another piece in the puzzle, since we provide an explanation for the protective biochemical changes induced by physical exercise that prevent the brain from being damaged during stress.”

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Stressful situations show the head and the heart don’t always agree

depressionThe head and the heart of people who suffer from high levels of anxiety react to stressful situations differently, researchers at the University of Birmingham have found.

The research, which was presented at the annual meeting of the American Psychosomatic Society, showed that the way people with high levels of anxiety feel that they are responding to a task and the way their body actually responds to the task are not related to each other.

Researchers from the School of Sport, Exercise and Rehabilitation Sciences, measured general everyday anxiety levels in 180 adolescents and then recorded their heart rate while they were resting and during a psychological stress task, such as a maths test under time pressure with social evaluation, in the laboratory. They used the difference between heart rate during the stress task compared to rest to determine their actual biological responses.

They found that people with higher anxiety in everyday life reported higher somatic symptoms (eg, feeling that their heart is racing) immediately before and during the stress task. However, there were no associations between people’s actual biological responses to stress and somatic symptoms during stress. There were also no associations between people’s biological responses and general anxiety.

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Study Reveals Working Moms Experience More Stress than Dads on Family Matters

Although working mothers and fathers are almost as likely to think about family matters throughout the day, only for mothers is this type of mental labor associated with increased stress and negative emotions, according to new research to be presented at the 108th Annual Meeting of the American Sociological Association.

“I assume that because mothers bear the major responsibility for childcare and family life, when they think about family matters, they tend to think about the less pleasant aspects of it — such as needing to pick up a child from daycare or having to schedule a doctor’s appointment for a sick kid — and are more likely to be worried,” said study author Shira Offer, an assistant professor in the Department of Sociology and Anthropology at Bar-Ilan University in Israel.

depressionMuch has been written about the unequal division of household labor and childcare, but the overwhelming majority of studies in this field examine specific behaviors, Offer said. “These studies focus on the physical aspect of tasks and demands, which can be measured and quantified relatively easily,” she said. “However, much of the work we do, both paid and unpaid, takes place in our mind. We are often preoccupied with the things we have to do, we often worry about them, and feel stressed not to forget to do them or to do them on time. These thoughts and concerns — mental labor — can impair our performance, make it difficult to focus on tasks, and even hurt our sleep. This mental labor is the focus of my study.”

The study relies on data from the 500 Family Study, a multi-method investigation of how middle-class families balance family and work experiences. The 500 Family Study collected comprehensive information from 1999 to 2000 on families living in eight urban and suburban communities across the United States. Most parents in the 500 Family Study are highly educated, employed in professional occupations, and work, on average, longer hours and report higher earnings than do middle-class families in other, nationally representative samples. Although the 500 Family Study is not a representative sample of families in the U.S., it reflects one of the most time pressured segments of the population. Offer’s study uses a subsample from the 500 Family Study, consisting of 402 mothers and 291 fathers in dual-earner families who completed a survey and a time diary that collects information about the content and context of individuals’ daily experiences, as well as the emotions associated with them, in the course of a week.

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