Category: Stress

 Psychology students at Queen's University have discovered similarities between child soldier trauma in Uganda and those children caught up in Northern Ireland's Troubles.

Post-graduate students from the Doctoral Programme in Educational, Child and Adolescent Psychology at Queen's recently travelled to Uganda to a school for ex-child soldiers. Their study analysed the levels of post-traumatic stress among ex-soldiers, explained the symptoms of trauma to the children and offered psychological therapy to the most traumatised children.

The children in the school were former abductees of the Lord's Resistance Army, a group notorious for kidnapping children, brutalising them and forcing them to become soldiers and sex slaves. Over 35,000 children are estimated to have been abducted over the last twenty-four years.

Paul O'Callaghan, one of the students leading the study said: "We screened 205 children for Post Traumatic Stress Disorder (PTSD), anxiety and depression. We found that even four years after witnessing traumatic war events, rates of psychological distress were very high with 58 per cent of the children showing PTSD symptoms and 34 per cent having depression and anxiety.

"The study highlighted a large prevalence of 'traumatic bonding' — where children adopt an abuser's views, attitudes and behaviours. The study found that over time some of the children began to identify more and more with the values and attitudes of their captors and even began to blame the victims for the violence they were subjected to.

He added: "Most remarkably our research showed that the most disturbing thing for the child soldiers was not the murders, massacres, torture or atrocities that they witnessed, instead, it was the death of their mothers during the war. The trauma and psychological distress of those who had lost their mother was much greater than those who had not.

"Although this research among child soldiers in Uganda may seem far removed from the lives of children in Northern Ireland there are strong parallels in the shifting sense of identity that can occur with children here who may initially have been coerced into joining criminal or paramilitary organisations but then go on to internalise the values, justifications and methods of these organisations over time."

The multi-disciplinary research team at Queen's School of Psychology are continuing their work pioneering a group-based mental health intervention specifically designed to treat psychological distress among child soldiers the Democratic Republic of Congo this summer.

Their work is being released in advance of 'Red Hand Day', a worldwide annual commemoration day on 12 February to draw attention to the plight of the 250,000 children who are currently forced to serve as soldiers in wars and armed conflicts, and to remember the thousands who have lost their lives as a result.

— Post-traumatic stress disorder can affect soldiers after combat or ordinary people who have undergone harrowing experiences. Of course, feelings of anxiety are normal and even desirable — they are part of what helps us survive in a world of real threats. But no less crucial is the return to normal — the slowing of the heartbeat and relaxation of tension — after the threat has passed. People who have a hard time "turning off" their stress response are candidates for post-traumatic stress syndrome, as well as anorexia, anxiety disorders and depression.

How does the body recover from responding to shock or acute stress? This question is at the heart of research conducted by Dr. Alon Chen of the Institute's Neurobiology Department. The response to stress begins in the brain, and Chen concentrates on a family of proteins that play a prominent role in regulating this mechanism. One protein in the family — CRF — is known to initiate a chain of events that occurs when we cope with pressure, and scientists have hypothesized that other members of the family are involved in shutting down that chain. In research that appeared in the Proceedings of the National Academy of Sciences (PNAS), Chen and his team have now, for the first time, provided sound evidence that three family members known as urocortin 1, 2 and 3 — are responsible for turning off the stress response.

The research group, including Adi Neufeld Cohen, Dr. Michael Tsoory, Dmitriy Getselter, and Shosh Gil, created genetically engineered mice that don't produce the three urocortin proteins. Before they were exposed to stress, these mice acted just like the control mice, showing no unusual anxiety. When the scientists stressed the mice, both groups reacted in the same way, showing clear signs of distress. Differences between the groups only appeared when they were checked 24 hours after the stressful episode: While the control mice had returned to their normal behavior, appearing to have recovered completely from the shock, the engineered mice were still showing the same levels of anxiety the scientists had observed immediately following their exposure to the stress.

Clearly, the urocortin proteins are crucial for returning to normal, but how, exactly, do they do this? To identify the mechanism for the proteins' activity, Chen and his team tested both groups of mice for expression levels of a number of genes known to be involved in the stress response. They found that gene expression levels remained constant during and after stress in the engineered mice, whereas patterns of gene expression in the control mice had changed quite a bit 24 hours after the fact. In other words, without the urocortin system, the "return to normal" program couldn't be activated.

Chen: "Our findings imply that the urocortin system plays a central role in regulating stress responses, and this may have implications for such diseases as anxiety disorders, depression and anorexia. The genetically engineered mice we created could be effective research models for these diseases."

Dr. Alon Chen's research is supported by the Nella and Leon Benoziyo Center for Neurosciences; the Nella and Leon Benoziyo Center for Neurological Diseases; the Carl and Micaela Einhorn-Dominic Brain Research Institute; the Irwin Green Alzheimer's Research Fund; the Mark Besen and the Pratt Foundation, Australia; the Roberto and Renata Ruhman, Brazil; and Martine Turcotte, Canada. Dr. Chen is the incumbent of the Philip Harris and Gerald Ronson Career Development Chair.

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Journal Reference:

1. A. Neufeld-Cohen, M. M. Tsoory, A. K. Evans, D. Getselter, S. Gil, C. A. Lowry, W. W. Vale, A. Chen. A triple urocortin knockout mouse model reveals an essential role for urocortins in stress recovery. Proceedings of the National Academy of Sciences, 2010; 107 (44): 19020 DOI: 10.1073/pnas.1013761107

A new study provides insight into how stress impacts the brain and may help to explain why some individuals are predisposed to depression when they experience chronic stress. The research, published by Cell Press in the January 27 issue of the journal Neuron, reveals complex molecular mechanisms associated with chronic stress and may help to guide new treatment strategies for depression.

"Many individuals exposed to stressful events do not show signs or symptoms of depression; however, some individuals exposed to psychological stress are predisposed to major depression," explains senior study author, Dr. Yoshifumi Watanabe, from Yamaguchi University in Japan. "Thus far, the molecular mechanisms underlying the susceptibility and adaptation to chronic stress within the brain are poorly understood."

Dr. Watanabe, coauthor Dr. Shusaku Uchida and their colleagues used two genetically distinct mouse strains that exhibit different behavioral responses to chronic stress to look for genetic mechanisms associated with vulnerability to stressful events. The researchers observed that, in contrast to the stress-resilient mice, the stress-vulnerable mice exhibited depression-like behaviors when exposed to chronic mild stress (environmental and social stressors that do not include food or water deprivation).

The stress-vulnerable mice had a lower level of gene expression for glial cell-derived neurotrophic factor (Gdnf). Neurotrophic factors are known to be important for regulation of brain plasticity and have been implicated in depression. The reduced level of Gdnf expression was the result of DNA methylation and histone modifications. These changes, called epigenetic modifications, and the depressive behaviors were reversed by treatment of the stress-vulnerable mice with antidepressants.

"Dynamic epigenetic regulations of the Gdnf gene play important roles in determining both the susceptibility and the adaptation responses to chronic stressful events," concludes Dr. Uchida. "Elucidation of the mechanisms underlying the modulations of HDAC2 expression, histone modifications, and DNA methylation influenced by chronic mild stress could lead to novel approaches for the treatment of depression."

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Journal Reference:

1. Shusaku Uchida, Kumiko Hara, Ayumi Kobayashi, Koji Otsuki, Hirotaka Yamagata, Teruyuki Hobara, Takayoshi Suzuki, Naoki Miyata, Yoshifumi Watanabe. Epigenetic Status of Gdnf in the Ventral Striatum Determines Susceptibility and Adaptation to Daily Stressful Events. Neuron, 2011; 69 (2): 359-372 DOI: 10.1016/j.neuron.2010.12.023

— A workplace's key employees may be at the greatest risk of experiencing high levels of work stress, according to a new study by the Centre for Addiction and Mental Health (CAMH).

In a survey of 2,737 workers, 18 per cent reported that their job was "highly stressful."

The odds of having high stress were greater if workers were managers or professionals, if they thought their poor job performance could negatively affect others, or if they worked long or variable hours. The study was published in this month's International Journal of Occupational and Environmental Medicine.

"The people who report high stress are the ones most invested in their jobs," says Dr. Carolyn Dewa, Senior Scientist and Head of CAMH's Work and Well-being Research and Evaluation Program. "Employers should be very concerned with keeping this population healthy. From a business perspective, it is in a company's best interest to support these workers."

The job characteristics associated with stress pointed to workers who were engaged and responsible. If workers felt their poor job performance could result in any physical injury, damage to company's equipment or reputation, or a financial loss, they were twice as likely to report high stress.

Having a worksite remote from their home, or having to entertain or travel for their jobs also increased the odds of being stressed. So did variable hours such as being on call, doing shift work or having a compressed work week.

Chronic stress can lead to burnout, and can worsen existing mental health problems or physical disability.

The study's goal was to learn how workers view their responsibilities and job characteristics, and their experience with stress. This information could be used to help develop interventions targeting both workers and their work environment, which is considered a more effective approach.

"It is important that employees have access to resources that address their mental health concerns. In the long run, these interventions can help save some of the annual $17 billion in lost productivity in Canada," said Dewa. "Employers should be asking, 'What am I doing to reduce stress in my most valuable people?'"

The survey included Alberta adults aged 18 to 65 who had worked the previous year in full range of settings, including offices, manufacturing, construction, farming and services, among others. Dewa notes, "These sources of stress that we identified will be the same for Canadian workers wherever they are based, as they held true across different locations and workplaces in our survey."

On the other end of the scale, 82 per cent of workers reported low or no stress. This group was more likely to be male, single, under the age of 25 or work in a small business. In addition, if workers were satisfied with their jobs, they were less likely to identify their jobs as being highly stressful.

Compared with the rest of Canada, Alberta reports slightly lower levels of stress than the rest of the country, the study notes.

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Journal Reference:

1. CS Dewa, AH Thompson, P Jacobs. Relationships between Job Stress and Worker Perceived Responsibilities and Job Characteristics. International Journal of Occupational and Environmental Medicine, Vol 2, No 1 January 2011

— A study of soldiers who took part in the ISAF mission in Afghanistan between 2008 and 2010 has found that their brains adapt when they are continuously exposed to stress. The perceived threat appears to be the major predictor of brain adaptation, rather than the actual events. In other words, if a roadside bomb goes off right in front of you, the degree to which you perceive this as threatening is what counts. This is what determines how the brain and the stress system adapt.

These results will be published in the journal Molecular Psychiatry on January 18.

Between 2008 and 2010 the researchers studied a group of 36 soldiers. Before and after taking part in the mission, the soldiers' brain activity was measured and compared with the brain activity of a control group of equal size who stayed at home. Unique to this study is that it is the first to use a control group. This control group, which stayed behind in the barracks in the Netherlands, had received similar combat training.

First study with control group

'Thanks to the design of our study, for the first time we can now conclude that the effects on the brain really are due to experiences in combat. The soldiers taking part in the ISAF mission in Afghanistan had their brains scanned twice. They also filled out questionnaires about their experiences during combat. The soldiers did not develop posttraumatic stress disorders (PTSD) but their experiences did have an effect on the neural circuits in the brain that regulate vigilance and that are also involved in controlling emotion. This effect persisted for at least two months after the soldiers returned home,' says Guido van Wingen of the Donders Institute for Brain, Cognition and Behaviour at Radboud University Nijmegen, first author of the study.

Military mental health study

This research is part of a long-term project in collaboration with the Military Mental Health Research Centre and the Rudolf Magnus Institute of Neuroscience in Utrecht. Activity in the amygdala and insula, the fear and vigilance centres in the brain, increases in all soldiers on mission. But the changes in the emotional control centre in the frontal lobe depend strongly on how they perceived threatening events during the mission. The researchers are now working on a follow-up study to see how long the changes in soldiers' heads remain, and whether or not those that perceived high levels of stress are also at higher risk of developing symptoms of posttraumatic stress.

Journal Reference:

1. G A van Wingen, E Geuze, E Vermetten, G Fernández. Perceived threat predicts the neural sequelae of combat stress. Molecular Psychiatry, 2011; DOI: 10.1038/mp.2010.132

 In the future, more and more products will be able to interpret what users are feeling and use that information in a smart way. To illustrate the power of this theory, researcher Miguel Bruns Alonso has developed a pen which can measure the stress levels of the person using it, and can actually help to reduce that stress. In experiments, the heart rate of people who used the anti-stress pen fell by an average of five percent.

On December 23, Miguel Bruns Alonso will receive his PhD degree from TU Delft based on his research into this subject.

Aggressive driving

There are already devices which can detect what the user is doing and feeling, and use this information in a smart way. This has now become a primary goal for product developers, and one which has already been achieved in automobiles, to some extent. For example, some cars can detect aggressive driving and intervene to counteract it. Delft PhD student Miguel Bruns Alonso decided to develop an anti-stress pen to demonstrate the potential of this relatively new concept in product design.

Nervous

Bruns, who studies industrial design, carried out various experiments during the course of his research, which showed that people tend to play with their pens in their hands when they are tense. It also seems that when they are encouraged to check these nervous movements, or make more gentle movements, it is possible to gain more control over a situation. 'Sensors in a pen could provide an unobtrusive way of measuring stress levels. Giving users the right feedback could then help them deal with their stress in a constructive way,' says Bruns.

Heart rate

'That is why I have developed a pen which can detect 'nervous' movements and determine whether the user is stressed. The pen also provides a counterweight to these movements using built-in electronics and electromagnets. When it detects the quicker movements associated with stress, the pen gradually becomes more difficult to move around. This encourages users to move in a more relaxed way, which in turn makes the pen yield more easily again.

Experiment

When the pen was evaluated in an experiment, people who received feedback on their behaviour had a lower heart rate (around 5 percent lower) than those who received no feedback. They experienced less psychological stress. However, neither were they aware that they were actually receiving any feedback on their behaviour. They also said that they did not feel any less stress.

Unobtrusive

'The conclusion to be drawn from this is that products which seek to reduce short-term stress should, preferably, intervene directly to modify that behaviour, rather than warning the user about their stress levels, for instance. This could allow products to reduce stress in an unobtrusive way.'

The anti-stress pen is at present a prototype and not (yet) available for purchase.

Studies on genetically engineered mice show that social stress activates the immune system and accelerates the development of atherosclerosis. Commonly used drugs to reduce blood pressure, however, may stop this process. This is the conclusion of a thesis presented at the University of Gothenburg, Sweden.

Several large studies have clearly shown that there is a correlation between psychosocial stress and the risk of developing cardiovascular disease. However, little is known about why this is the case.

"The aim of my thesis was to study the underlying mechanisms by which stress leads to atherosclerosis and subsequent cardiovascular disease," explains Evelina Bernberg, researcher at the Department of Molecular and Clinical Medicine, at the Sahlgrenska Academy.

The study has been conducted using mice that have been genetically modified to spontaneously develop atherosclerosis. Using mice as experimental animals allows the scientists to study cause and effect relationships in a controlled situation.

"We found that situations that disrupt the social environment in which the mice normally live increased atherosclerosis, while more physical forms of stress did not," explains Evelina Bernberg.

The scientists discovered that social stress increased blood levels of different markers of inflammation — which previously have been shown to accelerate the development of atherosclerosis.

"When the sympathetic nervous system is activated, adrenalin is released and this increases the heart rate. We also found some evidence that the sympathetic nervous system is responsible for the release of these inflammatory markers," Evelina Bernberg relates.

This release could be reduced by commonly used blood pressure medication, beta-blockers. The same beta-blockers also reduced atherosclerosis and the release of inflammatory markers in unstressed mice, showing that the sympathetic nervous system plays an important role in the development of atherosclerosis.

"Our studies suggest that social stress that activates the immune system is also the type of stress that can lead to the development of atherosclerosis, but we need to confirm whether our studies on gene-modified mice also reflect the situation in humans. It is possible that commonly used beta-blockers to a certain extent may prevent stress from leading to atherosclerosis," says Evelina Bernberg.

Atherosclerosis is initiated when cholesterol enters the blood vessel wall and atherosclerotic plaques are formed. Atherosclerosis is the major underlying cause of cardiovascular disease, such as angina, myocardial infarction and stroke.

— Five U.S. federal agencies recently cosponsored a set of expert work groups to formulate common data elements for research related to psychological adjustment and traumatic brain injury (TBI). Danny G. Kaloupek, PhD, associate professor of psychiatry and behavioral neuroscience at Boston University School of Medicine, chaired the work group on posttraumatic stress disorder (PTSD). Dr. Kaloupek's work at the National Center for PTSD at VA Boston Healthcare helped to guide identification of key PTSD-related characteristics and evidence-based measures that might be used in future research.

The results have been published in the November 2010 issue of Archives of Physical Medicine and Rehabilitation.

PTSD has an estimated prevalence of approximately 8 percent among U.S. adults, with much higher rates in subpopulations that include combat exposed military personnel. Potential for co-occurrence of psychological trauma and TBI exists because the same types of violent and life-threatening experiences can cause both conditions. In addition, some of the ways that PTSD can affect functioning are similar to the effects of an increasingly recognized condition labeled mild TBI. For these reasons, PTSD-related measures are likely to be relevant for many studies focusing on TBI.

The work group members were experts from across the U.S. selected to provide a wide range of PTSD expertise. Individual members reviewed published evidence and held discussions to determine which characteristics and factors are most important to future research. Eight categories were identified and reviewed including exposure to traumatic stressors, factors that moderate life stress, PTSD symptoms, mental health history, and domains of functioning.

The work group agreed with several previous recommendations on PTSD measurement but also expanded the scope and updated coverage of the evidence. They described common trends such as greater prevalence of PTSD in women than men and elevated risk for PTSD among ethnic minorities in the U.S. They also noted that childhood adversity involving abuse or serious deprivation has increasingly been recognized as an element in the lives of many people who subsequently develop PTSD. The work group was careful to recognize that the scientific advantages associated with a common set of measures must be balanced with the benefits of innovation and emerging evidence. As Dr. Kaloupek comments, "the work group effort contributes to greater integration of knowledge regarding PTSD and TBI, with the ultimate aim of benefiting the lives of those who experience trauma.

 — Disrupting the stress response in zebrafish generates behaviors that resemble depression, according to new research presented at Neuroscience 2010, the annual meeting of the Society for Neuroscience, held in San Diego.

"Our findings offer a molecular basis for the intuition that long-term emotional well-being depends on an individual's ability to cope with stress," said Herwig Baier, PhD, of the University of California, San Francisco, who led the study.

Zebrafish are popular model systems in many areas of biomedical research, but this is the first discovery of a zebrafish mutant with an apparent psychiatric disorder. When faced repeatedly with a stressful situation — isolation from others — the mutant fish stop swimming and hide in the corner of the tank for many minutes. This abnormal behavior was reversed by bathing the fish in water containing fluoxetine (Prozac), a selective serotonin reuptake inhibitor (SSRI) commonly prescribed for people with depression.

Baier and his colleagues found that the "depressed" zebrafish had a genetic mutation in the glucocorticoid receptor (GR) gene. One of the functions of GR is to "dial down" the secretion of stress hormones from the brain. Both too much and too little GR activity has been implicated in depression. The zebrafish mutant had little to no GR activity.

"We do not know yet if all this also holds true for people. But if it does, then strategies aimed at finding new antidepressant therapies should try to resurrect, rather than block, GR activity," Baier said.

Research was supported by the National Institutes of Health.

Oxytocin reduces anxiety in stressed animals, according to new research, but only if they recover in the presence of a friend.

The study was presented at Neuroscience 2010, the annual meeting of the Society for Neuroscience, held in San Diego.

"Work in the last two decades has propelled oxytocin toward the top of a list of potentially effective stress- and anxiety-reducing agents, largely due to its positive associations with mental health," said Jason Yee, PhD, a postdoctoral fellow in the laboratory of Sue Carter, PhD, at the University of Illinois at Chicago.

To explore oxytocin's effectiveness in relieving stress, Yee and his colleagues treated voles with oxytocin and then placed them in a wet cage, a stressor that mimics a flooded burrow the voles might experience in the wild. Then the researchers allowed the voles to recover in a dry cage, either by themselves or with another vole.

Most of the voles tried to escape the dry cage — an anxious behavior. However, the voles that received oxytocin and recovered with a companion showed less escape behaviors. These voles had high levels of oxytocin in their blood. In contrast, oxytocin was less effective at reducing anxious behaviors in voles that recovered by themselves. These voles had lower levels of oxytocin in their blood.

"When animals receive oxytocin and are given an opportunity to recuperate in the presence of a familiar partner, their bodies may release extra oxytocin, which in turn appears to facilitate a less anxious pattern of behavior," Yee said. The findings suggest that social contact is an important factor in oxytocin's ability to reduce anxiety.

Research was supported by the National Institute of Mental Health and the National Institute on Aging.