The incidence of allergies in children has increased over the past few decades, especially in the West (Europe). In Sweden, 30 to 40 percent of children have some kind of allergy. A combination of environmental and lifestyle factors during pregnancy and early infancy are thought to be responsible for the sharp rise in allergic diseases.

“Psychosocial factors and the stress hormone cortisol are associated with allergic diseases,” says Dr Fredrik Stenius of the Department of Clinical Research and Education at Stockholm South General Hospital. “Our study found that children with low salivary cortisol levels as infants have a lower prevalence of allergies during the first two years of life, compared to other children.”

The team has previously described a link between a lower prevalence of allergies in school children and an anthroposophic lifestyle.

“And now we’ve found the same link in infants from families that follow anthroposophic lifestyles, and that they have relatively low levels of cortisol,” adds Dr Stenius, who earned his PhD earlier in the year with a thesis on the subject.

The researchers believe that factors related to stress regulation also influence the development of infant allergies and will now monitor the infants from the neonate period and into childhood.

Material adapted from Karolinska Institutet.

Reference / Abstract
Stenius F, Borres M, Bottai M, Lilja G, Lindblad F, Pershagen G, Scheynius A, Swartz J, Theorell T, Alm J. ‘Salivary cortisol levels and allergy in children: The ALADDIN birth cohort.’ Journal of Allergy and Clinical Immunology, epub ahead of print 27 aug 2011, paper issue 2011 Dec;128(6):1335-9.

The stress-control pathway, more technically known as the Hypothalamus-Pituitary-Adrenal (HPA) axis, determines the levels of cortisol and other stress hormones in the human body. In addition to being implicated in the types of emotional and psychological stress that can lead to major depression, disorders of the stress-control pathway are also associated with obesity, premenstrual syndrome, postpartum depression, Cushing’s syndrome (hypercortisolism) and diseases including epilepsy and osteoporosis.

“We have identified a novel mechanism regulating the body’s response to stress by determining that neurosteroids are required to mount the physiological response to stress. Moreover, we were able to completely block the physiological response to stress as well as prevent stress-induced anxiety,” said author Jamie Maguire, PhD, assistant professor in the department of neuroscience at Tufts University School of Medicine and a member of the Neuroscience and Pharmacology & Experimental Therapeutics program faculties at the Sackler School of Graduate Biomedical Sciences at Tufts.

Using the brain tissues of adult mice, the research team identified mechanisms controlling the activity of Corticotrophin Releasing Hormone (CRH) neurons involved in the control of the stress pathway. By monitoring the activity of CRH neurons following stress and measuring levels of corticosterone in the blood, they found that the production of stress hormones required the action of neurosteroids on specific receptors on CRH neurons.

Apart from the finding that stress causes a neurosteroid-induced increase in blood corticosterone levels, the researchers also found that blocking the synthesis of neurosteroids is sufficient to block the stress-induced elevations in corticosterone and prevent stress-induced, anxiety-like behavior in mice. Previous research had identified the presence of specialized CRH-nerve-cell receptors in the HPA axis, but the findings had been controversial because of limited studies showing any connection between these receptors and the regulation of the CRH nerve cells.

“We have found a definite role of neurosteroids on the receptors regulating CRH nerve cells and the stress response. The data suggest that these receptors may be novel targets for control of the stress-control pathway. Our next work will focus on modulating these receptors to treat disorders associated with stress, including epilepsy and depression-like behaviors,” said Maguire.

The first author on the study is Jhimly Sarkar, PhD, formerly a postdoctoral associate in the neuroscience department at TUSM. Additional authors are Seth Wakefield, BS, a neuroscience graduate student at the Sackler School; Georgina MacKenzie, PhD, a postdoctoral associate in neuroscience at TUSM; and Stephen Moss, PhD, professor of neuroscience at TUSM and a member of the neuroscience program faculty at the Sackler School.

This study was supported by grants from the American Federation for Aging Research and the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health.

Material adapted from Tufts University.

Reference
Sarkar J, Wakefield S, MacKenzie G, Moss SJ, Maguire J. The Journal of Neuroscience. “Neurosteroidogenesis is required for the physiological response to stress: role of neurosteroid-sensitive GABAA receptors.” Published December 14, 2011, doi:10.1523/JNEUROSCI.2560-11.2011

Olshansky became interested in the subject when, in the summer of 2011, President Obama celebrated his 50th birthday and a flurry of news reports focused on his graying hair, pronounced wrinkles, and rapidly aging appearance.

“In the world of biology we know that you can’t actually measure the aging of an individual,” says Olshansky, professor of epidemiology at the UIC School of Public Health. “There isn’t any single test to actually measure how long you’ve aged from point A to point B, nor is it possible to predict specifically how long an individual will live.”

Using the assumption that presidents age at twice the normal rate, Olshansky calculated how long U.S. presidents would have been expected to live based on their age and the year they were inaugurated – and compared it to how long they actually lived. Aging at twice the normal rate was estimated by removing two days of life for every day in office (for example, a 4-year term led to a reduction in estimated remaining lifespan of 8 years).

Olshansky found that 23 of the 34 U.S. presidents who died from natural causes lived longer, and in many instances significantly longer, than predicted. Their average age at inauguration was 55.1 years. Four presidents who were assassinated were removed from the analysis.

Conventional wisdom suggests that the longevity of U.S. presidents is shortened due to the stresses of the office, but the average lifespan of the first eight presidents was 79.8 years – during a time when life expectancy at birth for men was less than 40.

“This is about how long females born in the U.S. today live,” Olshansky said.

The study also found that living ex-presidents have either already exceeded their predicted longevity at the time of their inauguration, or are likely to do so.

“We know that socioeconomic status has an extremely powerful effect on longevity now,” Olshansky said, “and it was likely to have been a factor in the past.” All but 10 U.S. presidents were college educated; all were wealthy; and all had access to health care. “We don’t die from gray hair and wrinkled skin,” said Olshansky. “What we’re seeing in President Obama is really not inconsistent with what we see for any other man his age in the U.S. or elsewhere.”

Material adapted from University of Illinois at Chicago.

This study also confirms that symptoms associated with the development of PTSD in police officers can be attenuated or prevented with specific and adapted intervention. These symptoms include dissociative reactions, emotional and physical reactions, a state of acute stress, depressive symptoms, and emotional coping responses to stress.

“Providing police officers with interventional support shortly after and in the weeks following a TE improves the chances of preventing PTSD,” explained André Marchand, lead author of the study, researcher at the Fernand-Seguin Research Centre of Louis-H. Lafontaine Hospital and Associate Professor at Université de Montréal. “The strategies for adapting to trauma, such as developing a stress-resistant personality and obtaining social support, can be improved through prevention components of police officer training programs,” said Mr. Marchand.

The descriptive analysis results show that police offers have different adaptation methods and strategies at their disposal in order to deal with a critical work-related event. In fact, the police officers stated that talking to their colleagues, obtaining peer support and taking part in leisure activities are particularly helpful after a traumatic event.

“The police offers involved in this study even advise their colleagues who experience this kind of event to consult a psychologist and are themselves open to the idea of receiving psychological support if need be,” said Mélissa Martin, co-author and psychologist at the Trauma Study Centre at Louis-H. Lafontaine Hospital.

This study, the first of its kind in Quebec, could be used as a reference for further research using a sample of Quebec police officers. The knowledge gained will help screen for and prevent PTSD. Recommendations based on this research will help police departments create strategies to both develop mechanisms that protect police officers from TE and decrease risk factors. This study could also have a significant impact on other people with a high risk of experiencing work-related TE (firefighters, paramedics, first-aid workers, first responders, etc.).

About the Study
Eighty-three policemen (63 men and 20 women) from the Service de Police de la Ville de Montréal (SPVM) and other police forces who had experienced a traumatic event volunteered for this prospective study and were evaluated at four intervals. Among the participants, 64% had to draw their guns, 11% fired their guns, while 28% of them used another weapon. A feeling of powerlessness in relation to the TE was reported by 80% of the police officers, and 59% of them felt a reaction of intense fear. More than half of the police officers said they experienced anger, 17% felt guilt, and 2% felt shame when the TE occurred.

Material adapted from Université de Montréal.

Rising Stress Levels Affect Emotional and Physical Health
The percentage of students in the UCLA survey reporting good or above-average high school emotional health dropped from 55.3 percent in 2009 to 51.9 percent in 2010. This marks the lowest level within the past 25 years.

Dr. Charles Elder, MD, lead author of the TM study, and investigator at Kaiser Permanente Center for Health Research, emphasized the important implications of the findings on reduced stress. “It is vital that we start addressing the high levels of emotional stress being reported by high school and college students. Decreased stress can have a positive impact on mental health, and can also reduce the risk for hypertension, obesity, and diabetes—major risk factors for heart disease,” explained Dr. Elder.

Educational research has also linked student stress to negative school behavior and poor academic performance.

Promising Findings for Education
“These new findings on reduced stress, along with the recent research on academic achievement gains, hold tremendous promise for public education,” said Sanford Nidich, EdD, principal investigator, and professor of education at Maharishi University of Management. “There is a growing body of evidence showing Transcendental Meditation to be an easy to implement, value-added educational program that promotes emotional health and increases academic achievement in at-risk students,” said Dr. Nidich.

A total of 106 secondary school students, 87% racial and ethnic minorities, took part in the study. Results showed that over a four-month period, students practicing Transcendental Meditation as part of their schools’ Quiet Time program exhibited significant reductions in psychological distress factors compared to controls.

This graph shows a 36 percent reduction in psychological distress in 106 at-risk racial and ethnic minority students practicing the Transcendental Meditation technique compared to controls over a period of 4 months (p=.010). Significant decreases were also found in trait anxiety and depressive symptoms. Credit: Maharishi University of Management

According to James Dierke, 2008 National Association of Secondary School Principals—National Middle School Principal of the Year, “Stress is the number one enemy of public education, especially in inner-city schools. It creates tension, violence, and compromises the cognitive and psychological capacity of students to learn and grow. The TM/Quiet Time program is the most powerful, effective program I have come across in my 39 years as a public school educator for addressing this problem. It is nourishing children and providing them an immensely valuable tool for life. It is saving lives.”

A summary of the study results were as follows:

• This study evaluated change in psychological distress factors in students practicing the Transcendental Meditation program compared to non-meditating controls. A total of 106 students (68 meditating and 38 non-meditating students), took part in the study. The study included students from four public secondary schools.
• Eighty-seven percent were racial and ethnic minority students, including 26% Hispanic, 25% African American, and 19% American Indian.
• The Transcendental Meditation program was practiced in class twice a day as part of the schools’ Quiet Time program for four months prior to posttesting.
• The Transcendental Meditation program was taught in the context of school-wide Quiet Time programs in which students voluntarily chose the Quiet Time program in which they wanted to participate.
• Transcendental Meditation is a simple, natural, effortless technique that allows the mind to settle down and experience a silent yet awake state of awareness, a state of “restful alertness.” Practice of this stress-reduction program does not involve any change in beliefs, values, religion, or lifestyle.
• Compared to eyes-closed rest, research has found that Transcendental Meditation practice is characterized by decreased activation or arousal of the autonomic nervous system, as reflected in decreased breath rate and lower sympathetic nervous system activity. The Transcendental Meditation program has been shown to increase electroencephalographic (EEG) brain integration and coherence, especially in the frontal area of the brain, responsible for higher-order processing.
• Other published research on high school and college students has shown reduced psychological distress, improved positive coping ability, decreased blood pressure, reduced cardiovascular reactivity to stressful stimuli, reduced absenteeism, and decreased school suspensions.
• Results of the current study indicated significant reductions in overall psychological distress (p=.010) and trait anxiety (p=.035) compared to controls. Within-in group differences in depressive symptoms were found for meditating students (p=.003).

Material adapted from Maharishi University of Management.

“The findings suggest that if young people can get improvements from dietary supplements, then the elderly and people at high risk for certain diseases might benefit even more,” said Janice Kiecolt-Glaser, professor of psychiatry and author of the study, which was published this month in the journal Brain, Behavior and Immunity.

“The more we understand about the complex interplay between inflammation and immunity, the closer we’ll get to figuring out which lifestyle choices and changes have the biggest impact on long term health.”

Omega-3 polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have long been considered as positive additives to the diet.

Earlier research suggested that the compounds might play a role in reducing the level of cytokines in the body, compounds that promote inflammation, and perhaps even reduce depression. Psychological stress has repeatedly been shown to increase cytokine production so the researchers wondered if increasing omega-3 might mitigate that process, reducing inflammation.

To test their theory, they turned to a familiar group of research subjects – medical students. Some of the earliest work these scientists showed that stress from important medical school tests lowered students’ immune status.

“We hypothesized that giving some students omega-3 supplements would decrease their production of proinflammatory cytokines, compared to other students who only received a placebo,” explained Kiecolt-Glaser. “We thought the omega-3 would reduce the stress-induced increase in cytokines that normally arose from nervousness over the tests.”

The team assembled a field of 68 first- and second-year medical students who volunteered for the clinical trial. Half the students received omega-3 supplements while the other half were given placebo pills. The students were randomly divided into six groups, all of which were interviewed six times during the study.

At each visit, blood samples were drawn from the students who also completed a battery of psychological surveys intended to gauge their levels of stress, anxiety, or depression. The students also completed questionnaires about their diet during the previous weeks.

“The omega-3 supplement the students received was probably about four or five times the amount of fish oil you’d get from a daily serving of salmon,” explained Martha Belury, professor of human nutrition and co-author in the study.

Part of the study, however, didn’t go according to plans.

Changes in the medical curriculum and the distribution of major tests throughout the year, rather than during a tense three-day period as was done in the past, removed much of the stress that medical students had shown in past studies.

“These students were not anxious. They weren’t really stressed. They were actually sleeping well throughout this period, so we didn’t get the stress effect we had expected,” Kiecolt-Glaser said.

But the psychological surveys clearly showed an important change in anxiety among the students: Those receiving the omega-3 showed a 20 percent reduction in anxiety compared to the placebo group. An analysis of the of the blood samples from the medical students showed similar important results.

“We took measurements of the cytokines in the blood serum, as well as measured the productivity of cells that produced two important cytokines, interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFα),” said Ron Glaser, professor of molecular virology, immunology & medical genetics and director of the Institute for Behavioral Medicine Research.

“We saw a 14 percent reduction in the amounts of IL-6 among the students receiving the omega-3.” Since the cytokines foster inflammation, “anything we can do to reduce cytokines is a big plus in dealing with the overall health of people at risk for many diseases,” he said.

Inflammation is a natural immune response that helps the body heal, but it also can play a harmful role in a host of diseases ranging from arthritis to heart disease to cancer.
Even though the study showed omega-3 supplements can reduce both anxiety and inflammation – and some of the researchers said that they take omega-3 supplements – the researchers are not ready to recommend that the public start taking them daily.

“It may be too early to recommend a broad use of omega-3 supplements, especially considering the cost and the limited supplies of fish needed to supply the oil,” Belury said. “People should just consider increasing their omega-3 through their diet.”

Also working on the research with Kiecolt-Glaser, Glaser and Belury were William Malarkey, professor emeritus of internal medicine, and Rebecca Andridge, an assistant professor of public health.

Material adapted from Ohio State University Center for Clinical and Translational Science.

The study was published in the most recent issue of the journal Pharmacology, Biochemistry and Behaviour.

The study involved 58 healthy people who were divided into two groups on the basis of whether they came from a family with a drink problem or not. Both groups were randomly assigned to two experimental situations, one of which was more stressful and involved solving mathematical problems under timed conditions in public. The two groups were subsequently allowed to drink alcohol in an experimental consumption test or a placebo, depending on which situation they had been randomly assigned.

“The results show that people with parents who have a history of alcohol abuse drink more than others when exposed to stress,” says Söderpalm Gordh.

This behavior can have negative consequences in the long term. It is no secret that people who consume large quantities of alcohol every time they drink run a higher risk of developing a dependency in the future.

“If alcohol relaxes you when you’re stressed, then you should try to find other ways of calming yourself down – relaxation exercises, for example,” says Söderpalm Gordh.

About Alcoholism
Alcoholism is usually divided into two categories: type I and type II. Type I is largely dependent on our genes’ interaction with the environment, for example the people we socialise with or the crises in our lives, while type II involves a considerable genetic risk of developing a drink problem, irrespective of our environment. Around 40% of the Swedish population has a close relative with a history of alcohol abuse.

Material adapted from University of Gothenburg.

“Being a teetotaler and a smoker were risk factors for mortality,” said Carolyn Aldwin, lead author of the study and a professor of human development and family sciences at Oregon State University. “So perhaps trying to keep your major stress events to a minimum, being married and having a glass of wine every night is the secret to a long life.”

This is the first study to show a direct link between stress trajectories and mortality in an aging population. Unlike previous studies that were conducted in a relatively short term with smaller sample sizes, this study was modified to document major stressors – such as death of a spouse or a putting a parent into a retirement home – that specifically affect middle-aged and older people.

“Most studies look at typical stress events that are geared at younger people, such as graduation, losing a job, having your first child,” Aldwin said. “I modified the stress measure to reflect the kinds of stress that we know impacts us more as we age, and even we were surprised at how strong the correlation between stress trajectories and mortality was.”

Aldwin said that previous studies examined stress only at one time point, while this study documented patterns of stress over a number of years.

The study, out now in the Journal of Aging Research, used longitudinal data surveying almost 1,000 middle-class and working-class men for an 18-year period, from 1985 to 2003. All the men in the study were picked because they had good health when they first signed up to be part of the Boston VA Normative Aging Study in the 1960s.

Those in the low-stress group experienced an average of two or fewer major life events in a year, compared with an average of three for the moderate group and up to six for the high stress group. One of the study’s most surprising findings was that the mortality risk was similar for the moderate versus high stress group.

“It seems there is a threshold and perhaps with anything more than two major life events a year and people just max out,” Aldwin said. “We were surprised the effect was not linear and that the moderate group had a similar risk of death to the high-risk group.”

While this study looked specifically at major life events and stress trajectories, Aldwin said the research group will next explore chronic daily stress as well as coping strategies.

“People are hardy, and they can deal with a few major stress events each year,” Aldwin said. “But our research suggests that long-term, even moderate stress can have lethal effects.”

Michael Levenson, Heidi Igarashi, Nuoo-Ting Molitor and John Molitor with Oregon State University and Avron Spiro III with Boston University all contributed to this study, which was funded by the National Institute on Aging as well as an award from the U.S. Department of Veterans Affairs.

Material adapted from Oregon State University.

Researcher Melissa Sturge-Apple

“Stress gets under your skin,” explains Melissa Sturge-Apple, assistant professor of psychology at the University of Rochester and lead author on the Development and Psychopathology paper to be published October 19. “It literally changes the way a mother’s body responds to the normal demands of small children and those changes make it much harder to parent positively.”

Although the effects of stress have been well documented in children and linked to a variety of diseases in adults, this is one of the first studies to look specifically at stress and parenting, according to the researchers. The findings point to the corrosive effects of poverty or depression on an individual’s physiology and help to explain why people feel and act the way they do when faced with ongoing psychological or economic pressure, she says.

“Stress is not just in our heads, it’s in our bodies,” says Sturge-Apple.

Researcher Fred Rogosch

The new monitor could become an important tool for measuring stress outside of the lab, the authors write. For example, it could be used in clinical settings as a kind of emotional biofeedback monitor, giving therapists a way to quantitatively gage which therapies work best for alleviating negative emotions, according to the researchers.

In the study, the researchers observed 153 mothers and their 17-to-19-month-old children in individual two-hour sessions. Using the wireless ECG monitor, each mother’s stress response was measured during a mildly distressing situation in which her child was left with a stranger for a few minutes. Later the mother and toddler were videotaped during unstructured playtime together.

The study showed that a mother’s stress system can be compromised by becoming either overactive or underactive. In mothers with higher depressive symptoms, stress responses were “hyperactive”, the researchers found. These moms’ heart rate patterns began higher, then spiked when their toddler was upset. After the mom was reunited with the child, their heart rate pattern remained elevated. During the free-play sessions, mothers with hyperactive stress responses engaged in the highest levels of hostility with their toddler, including derogatory comments, angry tone of voice, and rough physical interaction.

Mothers with higher depressive symptoms exhibited overactive stress responses, the "hyperarousal" pattern shown in red, while moms who struggled with poverty had underactive responses, the "hypoarousal" patter shown in blue. Each extreme was associated with distinct types of problematic parenting, from neglect and hostility to insensitivity. Credit: University of Rocheste

Although the popular image of depression is of someone who is listless and sad, Sturge-Apple points out that the study confirms what clinicians have long observed: that depression in mothers sometimes is linked to harsh, highly reactive parenting, not subdued mothering. This study helps to explain the biological basis of such behavior; the stress response systems of moms suffering from depression are on high alert, oversensitive to social stressors and unable to calm down, explains Sturge-Apple.

By contrast, study participants who struggled with poverty and lived in high-crime neighborhoods exhibited underactive, or “hypoactive,” stress response systems. Their heart rates patterns began lower and rose little during their child’s distress. During free play, these parents showed the highest levels of disengagement along with intrusive parenting. Although instructed to play with their children, these mothers were more likely to ignore their little ones and not respond to children’s bids for attention or play. When they were engaged, mothers with hyporesponsive stress activity were overbearing. The researchers argue that the dampened physiological response to a child’s anguish results from the “cumulative wear and tear … of living in poverty and dangerous neighborhoods.” Faced with threats and concerns on a daily basis, these moms’ stress systems simply become overwhelmed, concludes Sturge-Apple.

Material adapted from University of Rochester.

“We found that after diagnosis, black and Hispanic breast cancer patients reported higher levels of stress than whites, and that stress was associated with tumor aggressiveness,” said Garth H. Rauscher, Ph.D., associate professor of epidemiology in the division of epidemiology and biostatistics at the School of Public Health, University of Illinois at Chicago.

Rauscher and colleagues studied patient-reported perceptions of fear, anxiety and isolation, together referred to as psychosocial stress, and associations with breast cancer aggressiveness. He cautioned that patients’ stress levels were examined two to three months post-diagnosis.

The study included 989 breast cancer patients who were recently diagnosed; of those, 411 were non-Hispanic black, 397 were non-Hispanic white, and 181 were Hispanic. Results showed that psychosocial stress scores were higher for both black and Hispanic patients compared to white patients.

“Those who reported higher levels of stress tended to have more aggressive tumors. However, what we don’t know is if we had asked them the same question a year or five years before diagnosis, would we have seen the same association between stress and breast cancer aggressiveness?

“It’s not clear what’s driving this association. It may be that the level of stress in these patients’ lives influenced tumor aggressiveness. It may be that being diagnosed with a more aggressive tumor, with a more worrisome diagnosis and more stressful treatments, influenced reports of stress. It may be that both of these are playing a role in the association. We don’t know the answer to that question,” Rauscher said.

Material adapted from American Association for Cancer Research.

The study was conducted by researchers at Arizona State University as part of the Pathways Project, a larger longitudinal investigation of children’s social, psychological, and scholastic adjustment in school that is supported by the National Institutes of Health. It appears in the journal Child Development.

Socially withdrawn children who are classified as anxious-solitary are believed to experience competing motivations — they want to interact with peers, but the prospect of doing so causes anxiety that interferes with such interactions. In contrast, unsociable children are seen as having what’s called low approach and low avoidance motives—that is, they have little desire to interact with peers but are not repelled by the prospect of doing so; for these children, the overtures of peers do not make them feel anxious.

To learn more about students’ classroom behavior, emotions, and relations with peers, researchers collected students’ reports in which they nominated or rated their peers on a number of criteria (such as withdrawn behavior, aggressive behavior, prosocial behavior, and emotional sensitivity); teachers also reported on the same criteria. Reports were collected toward the beginning of the academic year and then again toward the end of the academic year. Using these reports, researchers classified students as anxious-solitary withdrawn, unsociable withdrawn, or non-withdrawn.

Compared with unsociable withdrawn youths and those who are not withdrawn, anxious-solitary children were found to be more emotionally sensitive and more likely to be excluded and victimized by their peers. They are also less likely to have friends, and when they do have friends, to have fewer than their peers and to lose friendships over time.

The researchers suggest that peer interaction is harder for anxious-solitary children because their anxiety interferes with their ability to form and maintain friendships. In contrast, unsociable youths tend to have more friends and to maintain those ties over time.

The study also found that having stable friendships protects children from being victimized by peers—and that both withdrawn and non-withdrawn children benefit from friendships in this way.

“Understanding withdrawn children’s friendships is important because they have fewer contacts with children their own age,” according to Gary Ladd, Cowden Distinguished Professor of Family and Human Development at Arizona State University, who led the study. “Because the consequences of peer isolation can be severe, it may be particularly important for withdrawn youth to develop and participate in friendships through organized sports, play dates, and other such activities.”

Society for Research in Child Development

Rats exposed to stress during early development inherit the effects of that stress to their offspring, largely expressed in behavior impairments but also characteristics of resilience, shows a new study from the University of Haifa, published in the journal Developmental Psychobiology. Providing environmental enrichment to the future mother rats had a remedial role on some of the negative effects. “The similarities between rats and humans raise the question of whether similar effects might transpire in humans; for example, exposure to war or natural disasters might have heritable effects,” explains Prof. Micah Leshem who headed the study.

The study, conducted by Prof. Leshem of the Department of Psychology at the University of Haifa along with Prof. Jay Schulkin of Georgetown University and postgraduate students Hiba Zaidan and Neta Kvetniy-Ferdman, set out to examine the cross-generational effects of early exposure to stress and enrichment. The researchers examined rats because of their resemblance to humans and their rapid rate of development and reproduction, which facilitates cross-generational studies.

The researchers studied 40 female rats weaned at 27 days of age. One group of these females – the control group – was then raised normally in individual cages; the second group was exposed to different stressors; the third was enriched; and the fourth group was both stressed and enriched. The matured rats were mated at 60 days, had normal pregnancies and births, and their offspring pups were divided into two groups – one raised normally, and the other raised in an enriched environment, so that the effect of “therapy” on the next generation could also be evaluated. The offspring groups were then evaluated with respect to social interaction, anxiety levels, ability to learn and capacity to cope with fear.

The study’s main findings showed that the early treatment of the mothers impacted their offspring behavior. Stress to the mothers reduced social interaction in their offspring, but improved their ability to learn to avoid distress. Male offspring were also better at coping with fear. Some of these changes were mitigated by enrichment to the mothers, so that stressing the mothers and then providing them with a “therapeutic” (enriched) environment, prevented some, but not all, of the effects in the next generation. Providing enrichment to the offspring also offset some of the inherited effects.

According to the researchers, their study, with other evidence, “suggests that evolution equipped the parent generation to sample its environment, and then, possibly via heritable epigenetic changes, to prepare the next generation to better cope with this environment,” Prof. Leshem explains. “It is important to investigate whether stressful experiences at a young age affect the next generation, and whether therapeutic experiences can minimize the trans-generational effects in humans too. As our study shows that the inheritance of the effects of adversity can be modified by timely intervention, this may have important educational and therapeutic implications,” he concludes.

Material adapted from University of Haifa.

Researcher Amy Przeworski, PhD

Individuals with GAD frequently put social relationships with family, friends, or coworkers at the top of their lists of worries, but the negative methods they use to cope — from over nurturing to extreme detachment—may be destructive.

Przeworski and colleagues at Penn State University observed that people in therapy for GAD manifested their worries in different ways based on how they interact with other people. In two studies, the researchers found four distinct interactive styles prominent among people with GAD — intrusive, cold, nonassertive, and exploitable.  Both studies supported the presence of these four interpersonal styles and their significant role in how people with GAD manifested their worrying.

“All individuals with these styles worried to the same extent and extreme, but manifested those worries in different ways,” Przeworski said.

Take the examples of two people with similar worries about someone’s health and safety. One person may exhibit that worry through frequent intrusive expressions of concern for the other person. Think of the parent or spouse who calls every five minutes to get an update on what’s happening. Another person may exhibit the worry by criticizing the behaviors that the person believes to be careless or reckless.

“The worry may be similar, but the impact of the worry on their interpersonal relationships would be extremely different. This suggests that interpersonal problems and worry may be intertwined,” Przeworski says.

She suggests that therapies to treat GAD should target both the worry and the related interpersonal problems.

Most treatments for GAD rely on cognitive behavioral therapy, a treatment that is usually successful for about 60 percent of people, a percentage considered successful in therapy. However, one way to improve therapy for worriers may be to integrate techniques that target the interpersonal relationship problems.

The researchers published their findings in the article, “Interpersonal Pathoplasticity in Individuals With Generalized Anxiety Disorder,” in the Journal of Abnormal Psychology and called for integrating the therapies for worrying and relationship issues.

In addition to Przeworski, contributing to the study were Pennsylvania State University researchers: Michelle G. Newman, Aaron L. Pincus, Michele B. Kasoff, Alissa S. Yamasaki and Louis G. Castonguay. The research was part of larger study supported by the National Institute of Mental Health.

Material adapted from Case Western Reserve University.

A new study found significant physiological instability one hour before patients reported feeling a panic attack. Credit: SMU Research

In a rare study in which patients were monitored around-the-clock, portable recorders captured changes in respiration, heart rate and other bodily functions, said Meuret, lead researcher on the study.

The new findings suggest sufferers of panic attacks may be highly sensitive to — but unaware of — an accumulating pattern of subtle physiological instabilities that occur before an attack, Meuret said. Monitoring data also showed patients were hyperventilating on a chronic basis.

“The results were just amazing,” Meuret said. “We found that in this hour preceding naturally occurring panic attacks, there was a lot of physiological instability. These significant physiological instabilities were not present during other times when the patient wasn’t about to have a panic attack.”

It is notable that patients reported the attacks as unexpected, lacking awareness of either the coming attack or their changing physiology.

“The changes don’t seem to enter the patient’s awareness,” Meuret said. “What they report is what happens at the end of the 60 minutes — that they’re having an out-of-the blue panic attack with a lot of intense physical sensations. We had expected the majority of the physiological activation would occur during and following the onset of the panic attack. But what we actually found was very little additional physiological change at that time.”

Unexpected attacks have been a mystery; little research to explain them
The diagnostic standard for psychological disorders, the DSM-IV, defines panic attacks as either expected or unexpected. Those that are expected, or cued, occur when a patient feels an attack is likely, such as in closed spaces, while driving or in a crowded place.

“But in an unexpected panic attack, the patient reports the attack to occur out-of-the-blue,” Meuret said. “They would say they were sitting watching TV when they were suddenly hit by a rush of symptoms, and there wasn’t anything that made it predictable.”

To sufferers and researchers alike, the attacks are a mystery.

Change-point analysis uncovered physiological instabilities one hour before attacks
Meuret and her colleagues discovered the significant physiological instabilities using change-point analysis, a statistical method that searches for points when changes occur in a “process” over time.

“This analysis allowed us to search through patients’ physiological data recorded in the hour before the onset of their panic attacks to determine if there were points at which the signals changed significantly,” said psychologist David Rosenfield of SMU, lead statistician on the project.

The study is significant not only for panic disorder, but also for other medical problems where symptoms and events have seemingly “out-of-the blue” onsets, such as seizures, strokes and even manic episodes.

“I think this method and study will ultimately help detect what’s going on before these unexpected events and help determine how to prevent them,” Meuret said. “If we know what’s happening before the event, it’s easier to treat it.”

Meuret, an assistant professor in the SMU Department of Psychology, reported the results in the journal Biological Psychiatry in the article “Do Unexpected Panic Attacks Occur Spontaneously?” Rosenfield is an associate professor in SMU’s Department of Psychology.

A multi-disciplinary collaboration, other authors on the study were psychologist Thomas Ritz, SMU Department of Psychology; psychologist Frank H. Wilhelm, University of Salzburg, Austria; electrical engineer Enlu Zhou, University of Illinois at Urbana-Champaign; and psychologist Ansgar Conrad and psychiatrist Walton T. Roth, both of Stanford University.

Subtle physical changes impact panic sufferers more severely
People with panic disorder probably won’t be surprised by the results, Meuret said.

By definition, the majority of the 13 symptoms of panic attack are physiological: shortness of breath, heart racing, dizziness, chest pain, sweating, hot flashes, trembling, choking, nausea and numbness. Only three are psychological: feeling of unreality, fear of losing control and fear of dying.

“Most patients obviously feel that there must be something going on physically,” Meuret said. “They worry they’re having a heart attack, suffocating or going to pass out. Our data doesn’t indicate there’s something inherently wrong with them physically, neither when they are at rest nor during panic. The fluctuations that we discovered are not extreme; they are subtle. But they seem to build up and may result in a notion that something catastrophic is going on.”

Notably, the researchers found that patients’ carbon dioxide, or C02, levels were in an abnormally low range, indicating the patients were chronically hyperventilating. These levels rose significantly shortly before panic onset and correlated with reports of anxiety, fear of dying and chest pain.

“It has been speculated, but never verified with data recordings in daily life, that increases in CO2 cause feelings of suffocation and can be panic triggers,” Meuret said.

Ambulatory monitoring of panic attack sufferers (simulated in this image) found that panic attacks that seem to strike out-of-the-blue are not without warning after all, according to new research from Southern Methodist University. Credit: SMU

Fanny pack monitor tracked physiological changes before, during and after attacks
To capture the physiological data, 43 patients wore the monitoring devices for 24 hours on two separate occasions. The researchers collected 1,960 hours of ambulatory monitoring data, including 13 unexpected panic attacks.

Participants, all of whom suffer from panic disorder, were each outfitted with an array of electrodes and sensors attached to various parts of their bodies.

The ambulatory monitoring device was toted in a small waist pack the patients wore. Also included was a portable capnometer to measure CO2 collected from exhaled breath. The physiological responses were recorded continuously as digital data in a time series.

Each monitoring pack included a “panic button.” Patients were instructed to press the button if they had an attack and to write down their symptoms. By triggering the panic button, patients inserted a marker into the time-series data, marking the moment the attack began.

The sensors measured eight physiological indices, including changes in respiration, such as how deep, fast or irregular people were breathing; cardiac activity; and evidence of sweating.

Data analysis found strikingly significant changes in the hour before attacks
From the nearly 2,000 hours of data, the change-point analysis program allowed the researchers to slice out 70-minute periods around each of the 13 panic attacks — from one hour before onset until 10 minutes after the attacks began.

For each index, the program checked for any significant change in the signal that remained stable over a specified period of time.

Those results were collapsed across all 13 panic attacks, with minute-by-minute averages. The information was then compared to a 70-minute control period randomly chosen during non-panic periods.

“We found 15 subtle but significant changes an hour before the onset of the panic attacks that followed a logical physiological pattern. These weren’t present during the non-panic period,” Meuret said.

“Why they occurred, we don’t know. We also can’t say necessarily they were causal for the panic attacks. But the changes were strikingly and significantly different to what was observed in the non-panic control period,” she said.

Findings prompt look at “panic” definition and treatment
The study’s results invite a reconsideration of the DSM diagnostic definition that separates “expected” from “unexpected” attacks, Meuret said.

Also, the study might explain why medication or interventions aimed at normalizing respiration for treating panic are effective, she said. Medication generally buffers arousal, keeping it low and regular, thereby preventing unexpected panic attacks.

For psychological treatments such as Cognitive Behavior Therapy (CBT), the results are more challenging. CBT requires a patient to focus on examining thoughts to prevent an attack.

“But a patient can’t work on something they don’t know is going to happen,” Meuret said.

New methodology can be universalized to other unexpected medical problems
The study’s use of change-point analysis can be applied to other medical issues. Traditional statistics are ineffective at analyzing such data, Meuret said, because they look only at level differences at pre-determined times and won’t find a signal for an unknown point.

“This study is a step toward more understanding and hopefully opening more doors for research on medical events that are difficult to predict. The hope is that we can then translate these findings into new therapies,” she said.

Material adapted from Southern Methodist University.

Previous research has found that women with fibromyalgia have lower-than-average cortisol levels, which contribute to pain, fatigue, and stress sensitivity. According to the study, participants’ saliva revealed elevated levels of total cortisol following a program of 75 minutes of hatha yoga twice weekly over the course of eight weeks.

“Ideally, our cortisol levels peak about 30-40 minutes after we get up in the morning and decline throughout the day until we’re ready to go to sleep,” says the study’s lead author, Kathryn Curtis, a PhD student in York’s Department of Psychology, Faculty of Health. “The secretion of the hormone, cortisol, is dysregulated in women with fibromyalgia” she says.

Cortisol is a steroid hormone that is produced and released by the adrenal gland and functions as a component of the hypothalamic-pituitary-adrenal (HPA) axis in response to stress.

“Hatha yoga promotes physical relaxation by decreasing activity of the sympathetic nervous system, which lowers heart rate and increases breath volume. We believe this in turn has a positive effect on the HPA axis,” says Curtis.

Participants completed questionnaires to determine pain intensity pre- and post-study; they reported significant reductions in pain and associated symptoms, as well as psychological benefits. They felt less helpless, were more accepting of their condition, and were less likely to “catastrophize” over current or future symptoms.

“We saw their levels of mindfulness increase – they were better able to detach from their psychological experience of pain,” Curtis says. Mindfulness is a form of active mental awareness rooted in Buddhist traditions; it is achieved by paying total attention to the present moment with a non-judgmental awareness of inner and outer experiences.

“Yoga promotes this concept – that we are not our bodies, our experiences, or our pain. This is extremely useful in the management of pain,” she says. “Moreover, our findings strongly suggest that psychological changes in turn affect our experience of physical pain.”

The study – Curtis’ thesis – was published yesterday in the Journal of Pain Research. It is co-authored by her supervisor, York professor Joel Katz, Canada Research Chair in Health Psychology, and Anna Osadchuk, a York University undergraduate student.

Material adapted from York University.

“Anecdotal reports suggest that alcohol dampens the physiological or negative emotional effects of stress but this has been hard to demonstrate in the lab,” said Emma Childs, research associate at The University of Chicago and corresponding author for the study. “Another way that stress could increase drinking is by altering alcohol’s effects. For example, if stress reduces the intoxicating effects of alcohol, individuals may drink more alcohol to produce the same effect.

Childs explained that the body’s reaction to stress involves separate physiological and emotional consequences that occur at different times after the stress. “For example,” she said, “the increase in heart rate and blood pressure, the release of cortisol, and also the increased feelings of tension and negative mood each reach a climax and dissipate at a different rate. Therefore, drinking more alcohol might have different effects, depending on how long after the stress a person drinks.”

Study subjects comprised 25 healthy men who participated in two sessions, one where they performed a stressful public speaking task and one with a non-stressful control task.

“The public speaking task we used is standardized and used by many researchers,” said Childs. “It reliably produces significant stress reactions, including increases in heart rate, blood pressure, cortisol, and feelings of tension. Moreover, because it is so widely used, the results can be compared directly to those from other studies. The public speaking task is also ecologically valid in that it represents a stressful event that many people experience outside the laboratory.”

After each task, participants received intravenously administered infusions containing alcohol (the equivalent of 2 standard drinks) and placebo. One group of participants (n = 11) received alcohol within one minute of completing the tasks, followed by the placebo 30 minutes later. The other group (n = 14) received the placebo infusion first, followed by the alcohol. Researchers measured subjective effects such as anxiety, stimulation, and desire for more alcohol, as well as physiological measures such as heart rate, blood pressure, and salivary cortisol before and at repeated intervals after the tasks and infusions.

“The results demonstrated bi-directional relationships between alcohol and stress,” said Childs. “Alcohol can change the way that the body deals with stress: it can decrease the hormone cortisol which the body releases to respond to stress, and it can prolong the feelings of tension produced by the stress. Stress can also change how alcohol makes a person feel: it can reduce the pleasant effects of alcohol or increase craving for more alcohol.”

Childs added that it is often hard to separate alcohol’s effects upon stress reactions from its effects on the perception of how stressful an experience is. “However, in our study we administered alcohol after the stressful experience, then examined the effects of alcohol on stress responses so ruling out any effect of alcohol upon perception of the stress. We showed that alcohol decreases the hormonal response to the stress, but also extends the negative subjective experience of the event. We also showed that stress decreased the pleasant effects of the alcohol. These findings illustrate a complex bi-directional interactions between stress and alcohol.”

In summary, said Childs, using alcohol to cope with stress may actually make a person’s response to stress worse, and prolong recovery from a stressor. “Stress may also alter the way that alcohol makes us feel in a way that increases the likelihood of drinking more alcohol,” she said. “Stress responses are beneficial in that they help us to react to adverse events. By altering the way that our bodies deal with stress, we may be increasing the risks of developing stress-related diseases, not the least of which is alcohol addiction.”

Material adapted from Alcoholism: Clinical & Experimental Research.

Researcher Patrick Davies

“Divergent reactions – both behaviorally and chemically – may be an evolutionary response to stress,” says Patrick Davies, professor of psychology at the University of Rochester and the lead author of the study. “These biological reactions may have provided our human ancestors with adaptive survival advantages. For example, dovish compliance may work better under some challenging family conditions, while hawkish aggression could be an asset in others.” This evolutionary perspective, says Davies, provides an important counterpoint to the prevailing idea in psychology that “there is one healthy way of being and that all behaviors are either adaptive or maladaptive.”

Coauthor Melissa Sturge-Apple agrees: “When it comes to healthy psychological behavior, one size does not fit all.” The assistant professor of psychology at the University of Rochester adds that the findings “give us insight into how basic behavioral patterns are also chemical patterns.”

Researcher Melissa Sturge-Apple

The study looked at 201 two-year-old toddlers, all from impoverished families with similar socio-economic profiles. Based on interviews and questionnaires with the mothers, the authors assessed children’s exposure to levels of aggression between parents.

The researchers also documented the dove or hawk tendencies of the toddlers in a variety of unfamiliar situations. Children who showed dovish tendencies were vigilant and submissive in the face of novelty. The toddlers clung to their mothers, cried, or froze when encountering new surroundings. Hawks used bold, aggressive, and dominating strategies for coping with challenge. They fearlessly explored unknown objects and new environments.

When the researchers exposed the children to a mildly stressful simulated telephone argument between their parents, distinct patterns of hormonal reactions emerged. Children exposed to high levels of interparental aggression at home showed different reactions to the telephone quarrel. Doves with parents who fought violently produced elevated levels of cortisol, a hormone that is thought to increase a person’s sensitivity to stress. Hawks from such stressful home environments put the breaks on cortisol production, which is regarded as a marker for diminishing experiences of danger and alarm.

This high-and-low-cortisol reactivity provides different developmental advantages and disadvantages, the authors write. Heightened cortisol levels characteristic of the doves were related to lower attention problems, but also put them at risk for developing anxiety and depression over time. By contrast, the lower cortisol levels for hawks in aggressive families were associated with lower anxiety problems; however, at the same time, these children were more prone to risky behavior, including attention and hyperactivity problems.

Material adapted from University of Rochester .

Drs. Jeffrey Zigman (right) and Jen-Chieh Chuang

“This helps explain certain complex eating behaviors and may be one of the mechanisms by which obesity develops in people exposed to psychosocial stress,” said Dr. Jeffrey Zigman, assistant professor of internal medicine and psychiatry and senior author of the study. “We think these findings are not just abstract and relevant only to mice, but likely are also relevant to humans.”

Scientists know that fasting causes ghrelin to be released from the gastrointestinal tract, and that the hormone then plays a role in sending hunger signals to the brain. Dr. Zigman’s laboratory has previously shown that chronic stress also causes elevated ghrelin levels, and that behaviors generally associated with depression and anxiety are minimized when ghrelin levels rise. In mice, these stress-induced rises in ghrelin lead to overeating and increased body weight, suggesting a mechanism for the increased prevalence of weight-related issues observed in humans with chronic stress and depression.

For this investigation, the researchers developed a mouse model to determine which hormones and what parts of the brain may play a role in controlling more complex eating behaviors that occur upon stress, particularly those that lead to the indulgence of comfort foods.

They subjected mice to a standard laboratory technique that induces social stress by exposure to more dominant “bully” mice. Such animals have been shown to be good models for studying depression and the effects of chronic stress and depression in humans.

Wild-type mice subjected to the stress gravitated toward a chamber where they had been trained to find pleasurable, fatty food – the mouse equivalent of “comfort food.” However, genetically-engineered mice, which were not able to respond to stress-induced increases in ghrelin, showed no preference toward the fatty food-paired chamber, and when exposed to the fatty food, did not eat as much as the wild-type animals.

“Our findings show that ghrelin signaling is crucial to this particular behavior and that the increase in ghrelin which occurs as a result of chronic stress is probably behind these food-reward behaviors,” Dr. Zigman said.

The study also showed that these effects of ghrelin are due to direct interaction with a subset of neurons that use catecholamines as a neurotransmitter. These include dopaminergic neurons in the brain’s ventral tegmental area, which is known to be associated with pleasure and reward behaviors.

The findings, he said, may make sense when considered from an evolutionary standpoint.

Our hunter-gatherer ancestors needed to be as calm as possible when it was time to venture out in search of food or risk becoming dinner themselves, said Dr. Zigman, who pointed out that ghrelin’s anti-depressant effects and its actions to help efficiently secure calorically-dense, tasty foods may have provided a survival advantage.

“Though it might have been beneficial to have these actions of ghrelin linked, now it seems to be a cause of a lot of morbidity in our modern society,” Dr. Zigman said. “Ultimately, these linkages also may present a large challenge to the development of therapeutics to treat and/or prevent obesity.”

The researchers next plan to investigate the molecular mechanisms by which ghrelin acts to cause these stress-associated food-reward behaviors.

Other UT Southwestern researchers involved in the study were Dr. Jen-Chieh Chuang, co-lead author and postdoctoral researcher in internal medicine; Sherri Osborne-Lawrence, senior research scientist; Dr. Michael Lutter, assistant professor of psychiatry; Dr. Ichiro Sakata, former postdoctoral researcher in internal medicine; and Dr. Mario Perello, co-lead author and former postdoctoral researcher in internal medicine. Dr. Perello currently works at the Multidisciplinary Institute of Cell Biology in Buenos Aires, Argentina. A researcher from Johns Hopkins University School of Medicine also contributed.

Material adapted from UT Southwestern Medical Center.

Researcher Ethan Moitra

“We definitely expected the symptoms to get worse over time, but we also thought the symptoms would get worse right away,” said Ethan Moitra, a postdoctoral researcher in the Department of Psychiatry and Human Behavior at the Warren Alpert Medical School of Brown University.

But even if the events do not seem to trigger an immediate panic attack, said Dr. Martin Keller, professor of psychiatry and human behavior and principal investigator of the research, patients, family members, or their psychiatrists need to keep their guard up.

“If they have the event and they are not feeling much different then maybe the vigilance on the individual’s part decreases somewhat,” Keller said. “With the knowledge we have, you may need to stay vigilant for three months or maybe longer. This is something you have to watch for.”

In their study, published in advance June 11 in the Journal of Affective Disorders, lead author Moitra, Keller, and their co-authors also found that panic symptoms did not seem to increase in advance of stressful life events, even if they were predictable, such as a divorce becoming official.

The study is based annual assessments of 418 adults with panic disorder or panic disorder with agoraphobia, who were enrolled in the Harvard/Brown Anxiety Research Project (HARP) between 1998 and 2004. Research staff asked the volunteers detailed, standardized questions about important events in their lives and their levels of anxiety.

A statistical analysis of the results found that for stressful life events in the categories of “work,” such as a demotion or layoff, or “friends/family/household,” such as a family argument, panic symptoms that had meandering severity before the event, increased steadily but gradually for at least 12 weeks afterward.

A stressful event occurred at week zero. The PSR (psychiatric status rating) shows no acute reaction, but the trend line increases steadily through week 12.

Stressful events in seven other categories, such as “crime/legal” or “deaths” did not seem to affect panic symptoms at all.

While the findings about the effect of some stressful life events on symptoms of people already diagnosed with panic disorder are new, other researchers have connected stress to panic attacks before. Stressful events are associated with the onset of panic disorder in the vast majority of cases, Moitra said.

Moitra said a possible biological explanation for the association is that stressful life events might exacerbate an underlying proclivity in people with panic disorder to perceive oncoming bouts of hyperventilation, which in turn lead to panic responses.

But while some stressful events have proven to be associated with changes in panic symptom levels, more research is needed to determine what kind of causal role stressful events may have.

“This may be one of those reasons why panic disorders can get worse,” Moitra said.

In addition to Moitra and Keller, other authors include Brown psychiatry and human behavior researchers Ingryd Dyck, Courtney Beard, Andri Bjornsson, and Nicholas Sibrava. Author Risa Weisberg is also affiliated with the Alpert Medical School’s Department of Family Medicine. The National Institutes of Health funded the research.

Material adapted from Brown University.

Stephen Mitroff, an assistant professor of psychology and neuroscience who led the experiment, says this area of cognitive psychology is important for improving homeland security and healthcare. He’s begun collaborating with the Transportation Security Agency at RDU airport and radiologists at Duke.

In earlier studies of this type, Mitroff’s team had wondered if the anxiety produced by being visible to a long line of frustrated travelers or having to interpret an image in a medical emergency might change a person’s performance on these sorts of tasks.

To simulate a stressful situation in this study, the researchers told the participants they might receive an unpredictable electrical shock for half of the trials that would be unrelated to their performance. Annoying but not painful electrical shocks are a well-established means of inducing anxiety in the lab. Only tests run without a shock were analyzed, focusing the research on the anxiety produced by anticipating a negative event. On the other half of the trials, participants heard a harmless tone.

Subjects performed about the same when searching for a single object whether anxious or not. But when the researchers added a second target, participants were more likely to miss the second object when anxious, despite spending the same amount of time looking at the image.

Missing a second target is a well-known issue called “satisfaction of search,” Mitroff said, and it is believed to account for about 40 percent of radiology misses. A person finds the first object and then simply fails to see the second one, even though they’re still looking.

Anxiety heightened the satisfaction-of-search problem, a finding which has important implications for the way we train and test searchers, Mitroff said.

The research was published online June 13 in Psychological Science. It was supported by the Army Research Office and the Institute for Homeland Security Solutions.

Material adapted from Duke University.

Reference
“Anticipatory anxiety hinders detection of a second target in dual-target search,” Matthew S. Cain, Joseph E. Dunsmoor, Kevin S. LaBar and Stephen R. Mitroff. Psychological Science, June 13, 2011. doi:10.1177/0956797611412393

Besides the personal impacts of this bias in the brain, it also makes people, and nations, vulnerable to being manipulated by threats, both real ones and “paper tigers.” Colbert is mocking those who play on fear, since we surely don’t need more efforts to keep fear alive.

Your Brain on Negative
Painful experiences range from subtle discomfort to extreme anguish — and there is a place for them. Sorrow can open the heart, anger can highlight injustices, fear can alert you to real threats, and remorse can help you take the high road next time.

But is there really any shortage of suffering in this world? Look at the faces of others, or your own, in the mirror, and see the marks of weariness, irritation, stress, disappointment, longing and worry. There’s plenty of challenge in life already — including unavoidable illness, loss of loved ones, old age and death — without needing a bias in your brain to give you an extra dose of pain each day.

Yet as my last post explored, your brain evolved exactly such a “negativity bias” in order to help your ancestors pass on their genes — a bias that produces lots of collateral damage today.

The Price of Pain
Painful experiences are more than passing discomforts. They produce lasting harms to your physical and mental health. When you’re feeling frazzled, pressured, down, hard on yourself or simply frustrated, that:

• Weakens your immune system
• Impairs nutrient absorption in your gastrointestinal system
• Increases vulnerabilities in your cardiovascular system
• Decreases your reproductive hormones; exacerbates PMS
• Disturbs your nervous system

Consider the famous saying: “Neurons that fire together, wire together.” This means that repeated painful experiences — even mild ones — tend to:

• Increase pessimism, anxiety and irritability
• Lower your mood
• Reduce ambition and positive risk-taking

In a couple, upsetting experiences foster mistrust, heightened sensitivity to relatively small issues, distance and vicious cycles. At much larger scales — between groups or nations — they do much the same.

So don’t take painful experiences lightly, neither the ones you get nor, honestly, the ones you give. Prevent them when you can, and help them pass through when you can’t.

Tilting Positive
Reducing negative experiences entails taking action in three domains: in the world (including your relationships), in your body and in your mind. All are important. In this brief post, I’m focusing on some things you can do in your mind — and those things are just a small fraction of all the resources available in the self help section of any bookstore.

For starters, take a stand for yourself, for feeling as good as you reasonably can. A stand for bearing painful experiences when they walk through the door — and a stand for encouraging them to keep on walking, all the way out of your mind.

This is not being at war with discomfort or distress, which would just add negativity, like trying to put out a fire with gasoline. Instead, it is being kind to yourself, wise and realistic about the toxic effects of painful experiences.

In effect, you’re simply saying to yourself something you’d say to a dear friend in pain: I want you to feel better, and I’m going to help you. Try saying that to yourself in your mind right now. How does it feel?

When emotional pain does come, even softly, try to hold it in a large space of awareness. In a traditional metaphor, imagine stirring a big spoon of salt into a cup of water and then drinking it: yuck. But then imagine stirring that spoonful into a clean bucket of water and then drinking a cup: it’s the same amount of salt — the same amount of worry or frustration, feeling inadequate or blue — but held in a larger context. Notice that awareness is without any edges, boundless like the sky, with thoughts and feelings passing through.

In your mind, watch out for how negative information, events or experiences can seem to overpower positive ones. For example, researchers have found that people typically will work harder or put up with more crud to avoid losing something than to gain the same thing. And they feel more contaminated by one fault than they feel cleansed or elevated by several virtues. Try to switch this around; for instance, pick some of your good qualities and keep seeing how they show up in your life this week.

Be careful whenever you feel stymied, frustrated or disappointed. As Martin Seligman and others have shown, humans (and other mammals) are very vulnerable to what’s called “learned helplessness” — developing a sense of futility, immobilization and passivity. Focus on where you can make a difference, where you do have power; it may only be inside your own mind, but that’s better than nothing at all.

In your relationships, be mindful of reacting more strongly to one negative event than to a bunch of positive ones. For example, studies have shown that it typically takes several positive interactions to make up for a single negative encounter. Pick an important relationship, and then really pay attention to what’s working in it; let yourself feel good about these things. Deal with the problems in this relationship, sure, but keep them in perspective.

Overall, whenever you remember, deliberately tilt toward the positive in your mind. That’s not looking at the world through rose-colored glasses. Given the negativity bias in the brain, you’re only leveling the playing field.

My next post will tackle a key consequence of the negativity bias: threat reactivity, which has many bad effects, including “paper tiger paranoia.” Following posts will explore more ways to address the negativity bias, from activating the soothing and recharging parasympathetic nervous system to mobilizing more of your inner resources to address the real challenges our planet faces.

* * *

Rick Hanson, Ph.D., is a neuropsychologist and founder of the Wellspring Institute for Neuroscience and Contemplative Wisdom. His work has been featured on the BBC, NPR, Consumer Reports Health, U.S. News and World Report, and Huffington Post, and he is the author of the best-selling Buddha’s Brain: The Practical Neuroscience of Happiness, Love, and Wisdom. He writes a weekly newsletter – Just One Thing – that suggests a simple practice each week that will bring you more joy, more fulfilling relationships, and more peace of mind and heart. If you wish, you can subscribe to Just One Thing here.

Some of those messages are true and worth heeding. For example, dumping carbon into the atmosphere must inevitably make the planet hotter; it’s basic physics.

But others are wildly exaggerated: the actual odds of a bad event on your airplane flight are “Threat Level Chartreuse” — a bucket of green paint with a drop of yellow.

How do we tell the difference between real threats and bogus ones? (This is important for many reasons; for one, chasing fake threats takes away resources from real issues.)

But it’s tough to do, since evolution has given us a brain with what scientists call a “negativity bias” that makes it prone to feeling threatened. This bias developed because the ancient mammals, primates, and early humans that were all mellow and fearless did not notice the shadow overhead or slither nearby that CHOMP! killed them. The ones that survived to pass on their genes were nervous and cranky, and we are their great-grandchildren, sitting atop the food chain, armed with nuclear weapons.

Stephen Colbert, relax: Mother Nature is on your side, already working hard to keep fear alive.

Your brain is continually looking for bad news. As soon as it finds some, it fixates on it with tunnel vision, fast-tracks it into memory storage, and then reactivates it at the least hint of anything even vaguely similar. But good news gets a kind of neural shrug: “uh, whatever.”

In effect, the brain is like Velcro for negative experiences but Teflon for positive ones.

All this makes human beings super-sensitive to apparent threats. Basically, in evolution, there are two kinds of mistakes: (1) You think there is a tiger in the bushes but there isn’t one, and (2) You think the coast is clear, no tiger in the bushes, but there really is one about to pounce.

These mistakes have very different consequences. The first one will make you anxious, but the second one will kill you. That’s why Mother Nature wants you to make the first mistake a thousand times over in order to avoid making the second mistake even once.

This hard-wired tendency toward fear affects individuals, groups (from couples to multinational corporations), and nations. It makes them overestimate threats, underestimate opportunities, and underestimate resources.

Of course we need to deal with real tigers, real threats, ranging from leaky roofs to the shaky economy, national debt, terrorism, and global warming. But “keeping fear alive” for tigers that are nonexistent, manageably small, or made out of paper has huge costs.

At the personal level, fear feels bad, wears down physical and mental health, and makes people duck for cover in life and play small. (These individual costs also drag down the economy.)

Nationally, feeling threatened gets intensified by the classic drumbeat of alarms about inner and outer enemies from people who are good at trumping hope with fear. The result? Paper tiger paranoia – which makes us over-invest in threat protection, under-invest in infrastructure, miss real tigers because we’re flooded with warnings about illusory or exaggerated ones, and over-react in ways that create new real tigers (like America’s longest war, in Iraq).

The solution? It’s to have the courage to see real tigers clearly and to deal with them effectively – and to refuse to be frightened and cowed by boys and girls crying tiger.

It also helps to get more skillful with your own brain: to understand how it makes you needlessly afraid, whether you’re talking with a family member, doing a project at work, or watching the news – and most importantly, what you can do about that by using your mind alone to change your brain for the better.

Which is what I’ll be exploring in my upcoming posts, including how to calm down threat reactivity, feel stronger and safer, recognize both real tigers and paper ones, and realize that in most situations most of the time, it is not “Threat Level Orange.”

Meanwhile, let’s not do anything more to keep fear alive. Mother Nature and Fox News are already doing a very good job there. Instead, let’s do more to keep courage alive.

A great first step is to laugh at paper tigers.

***

Rick Hanson, Ph.D., is a neuropsychologist and founder of the Wellspring Institute for Neuroscience and Contemplative Wisdom. His work has been featured on the BBC, NPR, Consumer Reports Health, U.S. News and World Report, and Huffington Post, and he is the author of the best-selling Buddha’s Brain: The Practical Neuroscience of Happiness, Love, and Wisdom. He writes a weekly newsletter – Just One Thing – that suggests a simple practice each week that will bring you more joy, more fulfilling relationships, and more peace of mind and heart. If you wish, you can subscribe to Just One Thing here.

“The exciting results provide stimulus for further investigating a microbial component to the causation of behavioral illnesses,” said Stephen Collins, professor of medicine and associate dean research, Michael G. DeGroote School of Medicine. Collins and Premysl Bercik, assistant professor of medicine, undertook the research in the Farncombe Family Digestive Health Research Institute.

For each person, the gut is home to about 1,000 trillium bacteria with which we live in harmony. These bacteria perform a number of functions vital to health: They harvest energy from the diet, protect against infections, and provide nutrition to cells in the gut. Any disruption can result in life-threatening conditions, such as antibiotic-induced colitis from infection with the “superbug” Clostridium difficile.

Working with healthy adult mice, the researchers showed that disrupting the normal bacterial content of the gut with antibiotics produced changes in behavior; the mice became less cautious or anxious. This change was accompanied by an increase in brain derived neurotrophic factor (BDNF), which has been linked to depression and anxiety.

When oral antibiotics were discontinued, bacteria in the gut returned to normal. “This was accompanied by restoration of normal behavior and brain chemistry,” Collins said.

To confirm that bacteria can influence behavior, the researchers colonized germ-free mice with bacteria taken from mice with a different behavioral pattern. They found that when germ-free mice with a genetic background associated with passive behavior were colonized with bacteria from mice with higher exploratory behavior, they became more active and daring. Similarly, normally active mice became more passive after receiving bacteria from mice whose genetic background is associated with passive behavior.

While previous research has focused on the role bacteria play in brain development early in life, Collins said this latest research indicates that while many factors determine behavior, the nature and stability of bacteria in the gut appear to influence behavior and any disruption from antibiotics or infection might produce changes in behavior.

Bercik said that these results lay the foundation for investigating the therapeutic potential of probiotic bacteria and their products in the treatment of behavioral disorders, particularly those associated with gastrointestinal conditions such as irritable bowel syndrome.

Material adapted from McMaster University.

“Previous research has shown that children of parents with bipolar disorder are four times as likely to develop mood disorders as those from parents without the condition,” says senior author Mark Ellenbogen, Canada Research Chair in Developmental Psychopathology at Concordia University and a member of the Centre for Research in Human Development. “The goal of our study was to determine how this is happening.”

Cortisol, the telltale hormone
Ellenbogen and colleagues had previously shown that cortisol levels in children with a parent affected by bipolar disorder were higher than kids whose parents were unaffected by the condition. The current study measured cortisol levels in these same individuals during chronic and episodic stress periods. In both circumstances, children of parents with bipolar disorder showed a greater increase in cortisol than those of parents without the disorder.

“Our study demonstrates that affected children are biologically more sensitive to the experience of stress in their natural and normal environment compared to unaffected peers,” says Ellenbogen. “This higher reactivity to stress might be one explanation of why these offspring end up developing disorders and is a clear risk factor to becoming ill later on.”

“We think we might be beginning to understand where we can intervene to actually prevent this increased sensitivity from developing,” continues Ellenbogen. “We believe this sensitivity develops during childhood and our suspicion is that if you could teach both parents and their offspring on how to cope with stress, how to deal with problems before they turn into larger significant stressors and difficulties, this would have a profound impact.”

About cortisol:
Cortisol is a hormone that is produced by the body in response to anxiety and researchers use cortisol to monitor the biological response to stress.

About bipolar disorder:
Bipolar disorder, which is also known as manic depression, is a treatable illness marked by extreme changes in mood, thought, energy and behavior. Bipolar disorder is also known as manic depression because a person’s mood can alternate between mania (highs) and depression (lows). These changes in mood, or “mood swings,” can last for hours, days, weeks or months.

Material adapted from Concordia University.

Scientists from Ohio State University’s Institute of Behavioral Medicine Research reported their results in the latest issue of the Journal of Neuroscience.

John Sheridan, professor of oral biology, and Jonathan Godbout, an assistant professor of molecular virology, immunology and medical genetics, turned to colonies of mice to make their discoveries.

Groups of mice living together quickly adopt a hierarchy ranging from dominant to subordinate. This vaguely political system controls the interaction among the animals. Once these patterns had been established, the researchers then added an additional, highly aggressive mouse to the mix for a two-hour period each day to disrupt the social hierarchy.

With no place to retreat, the mice were forced into conflicts with the new aggressor. After as few as three episodes with the aggressor, the original mice showed distinct signs of what the researchers considered “anxiety-like behaviors.” This kind of experiment creates a “social disruption” within the group of mice and is widely used to mimic psychological stress.

“These animals can’t flee, so they have to stand and fight,” Sheridan explained. “In doing so, they’re repeatedly defeated, creating a condition called “learned helplessness,” a condition closely linked to depression.

What Sheridan and Godbout saw was that the animals’ anxiety continued for a long time after the termination of the stressful episodes of defeat. “For two weeks or more after we stopped the stressor, we could still see this anxiety-like behavior,” Sheridan said.

The real discoveries came when the researchers analyzed what was happening in the animals’ brains and in their immune response.

“We found that in the stressed animals, a certain type of immune cell (myeloid progenitor cell, or MPC), produced in the bone marrow, entered the circulatory system and migrated to the brain,” explained Godbout.

These MPCs might normally relocate in this way to deal with an infection or an injury in the brain, but in this case, they moved solely because of the response to a social stressor, he said. The experiments showed that the number of these cells more than tripled in the brain following the stress.

Other immune cells called microglia, normally residing in the brain, also triggered an inflammatory response because of the stress. The researchers also noted that the stressor caused a particular activation pattern of neurons, or nerve cells, within the brain.

The response to social stress also caused an increase in the amounts of some inflammatory cytokines in the brain, including interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-a) which are linked to inflammation. These cytokine responses correlated with an insensitivity of MPCs to glucocorticoids, hormones that normally inhibit inflammation in the body.

So the research team saw these and other cellular changes occurring in the brain following the stress, at the same time they were seeing the behavioral changes – the anxiety-like behavior.

The findings are evidence of a two-way communication that’s existing between the body and the brain in times of stress, Sheridan said.

To test that apparent connection, they gave the mice injections of propranolol – a so-called “beta-blocker” drug often used for cardiac conditions – before they encountered the more aggressive mouse. In this case, the researchers saw no increase in IL-1 or TNF-a, no glucocorticoid insensitivity, and no long-lasting anxiety-like behavior in the test animals.

“If we treated the animal with a beta-blocker each night before we put the intruder in, it completely blocked the signal. The anxiety-like behavior never developed,” Godbout said.

“What this basically argues is that we may now have a new target for individuals who have extended anxiety-like behavior,” Sheridan said. “We may have a new target cell to think about in terms of new therapies.

“And since that cell (the MPCs traveling from the bone marrow) is coming from the periphery of the body, we might not need to resort to psychoactive drugs that can have adverse effects on the brain.”

Proving that, however, will take more animal studies and subsequent large studies using humans before this approach could be used clinically, he said.

Working with Sheridan and Godbout on the research were Eric Wohleb, Mark Hanke, Angela Corona, Nicole Powell, LaTonia Stiner, Michael Bailey and Randy Nelson, all of Ohio State.

Material adapted from Ohio State University.

The advance offers new hope for targeted treatment, or even prevention, of stress-related psychiatric disorders.

About 20% of the population experience some form of anxiety disorder at least once in their lives. The cumulative lifetime prevalence of all stress-related disorders is difficult to estimate but is probably higher than 30%.

Dr. Robert Pawlak, from the University of Leicester who led the UK team, said: “Stress-related disorders affect a large percentage of the population and generate an enormous personal, social and economic impact. It was previously known that certain individuals are more susceptible to detrimental effects of stress than others. Although the majority of us experience traumatic events, only some develop stress-associated psychiatric disorders such as depression, anxiety, or posttraumatic stress disorder [PTSD]. The reasons for this were not clear.”

Dr. Pawlak added that a lack of correspondence between the commonness of exposure to psychological trauma and the development of pathological anxiety prompted the researchers to look for factors that may make some individuals more vulnerable to stress than others.

Nerve cells (red) reach out and communicate with each other at junctions called synapses (green) that release chemicals to promote anxiety. (Credit: University of Leicester)

“We asked: What is the molecular basis of anxiety in response to noxious stimuli? How are stress-related environmental signals translated into proper behavioral responses? To investigate these problems we used a combination of genetic, molecular, electrophysiological, and behavioral approaches. This resulted in the discovery of a critical, previously unknown pathway mediating anxiety in response to stress.”

The study found that the emotional centre of the brain – the amygdala – reacts to stress by increasing production of a protein called neuropsin. This triggers a series of chemical events which in turn cause the amygdala to increase its activity. As a consequence, a gene is turned on that determines the stress response at a cellular level.

“We then examined behavioural consequences of the above series of cellular events caused by stress in the amygdala,” said Dr. Pawlak. “Studies in mice revealed that upon feeling stressed, they stayed away from zones in a maze where they felt unsafe. These were open and illuminated spaces they avoid when they are anxious.”

Newly discovered neurochemical cascade promoting stress-induced anxiety. Neuropsin interacts with cell membrane proteins NMDA and EphB2 to induce expression of the Fkbp5 gene. Credit: University of Leicester (click to enlarge)

Neuropsin was previously discovered by Professor Sadao Shiosaka, a co-author of the paper. This research, for which the bioinformatics modelling was done by Professor Ryszard Przewlocki and his team, has for the first time characterized its mechanism of action in controlling anxiety in the amygdala.

The study took four years to complete, during which scientists from the Department of Cell Physiology and Pharmacology collaborated with colleagues from the Medical Research Council Toxicology Unit at the University of Leicester, the Department of Molecular Neuropharmacology, Polish Academy of Sciences in Krakow, Poland and Nara Institute of Science and Technology in Japan. The work was supported by the European Union, the Medical Research Council and Medisearch – the Leicestershire Medical Research Foundation. The first author, Benjamin Attwood, sponsored by Medisearch, took 3 years off from his medical studies curriculum to complete the necessary experiments. He commented: “It has been a thoroughly absorbing project to uncover how our experiences can change the way we behave. Hopefully this will lead to help for people that have to live with the damaging consequences of traumatic experiences.”

Dr. Pawlak added: “We are tremendously excited about these findings. We know that all members of the neuropsin pathway are present in the human brain. They may play a similar role in humans and further research will be necessary to examine the potential of intervention therapies for controlling stress-induced behaviours.”

“Although research is now needed to translate our findings to the clinical situation, our discovery opens new possibilities for prevention and treatment of stress-related psychiatric disorders such as depression and posttraumatic stress disorder.”

Material adapted from University of Leicester.

Reference
Neuropsin cleaves EphB2 in the amygdala to control anxiety. Nature (DOI: 10.1038/nature09938).

Common stressful events included financial and relationship problems, difficult pregnancy, job loss, and issues with other children and major life stressors were events such as a death in the family.

Lead author, Registered Psychologist Dr. Monique Robinson, said while previous studies have shown a link between stress and poorer outcomes, this study goes further by analyzing the timing, amount, and kinds of events that lead to poorer outcomes.

“What we have found is that it is the overall number of stresses that is most related to child behavior outcomes,” Dr. Robinson said. “Two or fewer stresses during pregnancy are not associated with poor child behavioral development, but as the number of stresses increase to three or more, then the risks of more difficult child behavior increase.”

Dr Robinson said the actual type of stress experienced was of less importance than the number of stresses, and there was no specific risk associated with the timing of these stress events – early or late – in the pregnancy.

The analysis was undertaken on data from Western Australia’s long-term cohort Raine Study, which recruited nearly 3000 pregnant women and recorded life stress events experienced at 18 and 34 weeks of pregnancy, as well as collecting sociodemographic data. The mother’s experience of life stress events and child behavioral assessments were also recorded when the children were followed-up ages 2, 5, 8, 10, and 14 years using a questionnaire called the Child Behaviour Checklist.

The percentage of women with more than two stress events was 37.2%, while the percentage with six or more was 7.6%.

Dr. Robinson said the study should not make pregnant women stress further about the stress in their lives. “These types of analyses look at overall population risk, and of course individuals can have very differing responses,” Dr. Robinson said.

“Regardless of exposure to stress in the womb, a nurturing environment after birth can provide the child with enormous potential to change their course of development. This is known as “developmental plasticity,” which means that the brain can adapt and change as the child grows with a positive environment.

“The important message here is in how we as a community support pregnant women. If we think about people who lead stressful lives, they are most often linked with socioeconomic disadvantage. This research shows we should be targeting these women with support programs to ensure the stress does not negatively affect the unborn child.”

Dr. Robinson said further research is needed to understand the mechanisms behind how stress in pregnancy affects the developing baby, including the impact of maternal stress hormones, attachment and parenting issues and socioeconomic factors.

Material adapted from Research Australia.

Researchers, supported in part by NIMH, used a virus, genetic engineering and fiber-optics to control the pathway in the brain’s fear center with millisecond precision.

“Our findings reveal how balanced antagonistic brain pathways are continuously regulating anxiety,” explained Karl Deisseroth, M.D., Ph.D., of Stanford University, a practicing psychiatrist as well as a neuroscientist. “We have pinpointed an anxiety-quelling pathway and demonstrated a way to control it that may hold promise for new types of anti-anxiety treatments.”

NIMH grantees Deisseroth, Kay M. Tye, Ph.D., and colleagues, report on their findings March 17, 2011 in the journal Nature.

Optogenetic alchemy

Anxiety disorders are the most common type of psychiatric illness, affecting more than 1 in 4 people at some time during their lives. To understand the neural basis of these disorders, researchers are studying the workings of circuitry in the fear center, called the amygdala, in rodents.

Deisseroth’s team has pioneered a method, called optogenetics, of experimentally activating brain activity with light. They incorporate a protein borrowed from light-reactive organisms to make brain tissue similarly light-responsive. Previously, they used this tool to activate particular types of neurons. The new study is the first to use it to reversibly manipulate a specific projection of a neuron. It is also the first time the technique has been used to study anxiety as opposed to fear – a generalized state versus a transient reaction to an immediate threat.

The researchers borrowed a gene that codes for a light-sensitive protein from algae and delivered it to the amygdala pathway via a virus. In the algae, the protein’s function is to activate a pathway that causes the organism to swim toward blue spectrum light. Hence a blue light now activated the amygdala pathway. When they wanted to inhibit the pathway in response to light, they similarly borrowed a gene from a light-responsive bacterium that codes for a protein that inhibits a pathway in response to a particular spectrum of light — in this case amber — and infected the amygdala pathway with that gene.

When the researchers optogenetically activated whole neuronal cell bodies in the amygdala, it increased anxiety-like behavior: mice hunkered down in a protected corner of a maze and would not venture into more exposed areas. These and related findings led the researchers to hypothesize that they would get the same effect if they narrowed the focus of the activation to just a specific neuronal projection.

A post-doc’s eureka! moment

But it turned out that the opposite was true.

When they activated the projection with the blue laser, the engineered mice suddenly seemed to summon the courage to explore the more exposed parts of the maze that they would normally avoid (see video below).

“I was quite surprised. We did not see aversion. We did not see fear. We did not see any of these things I expected to see,” said Tye, whose post-doctoral study is supported by a NIMH-funded training grant. “I suddenly got this huge, dramatic effect of reduction in anxiety-related behaviors and I had to follow it up. So I pretty much dropped my original ideas of what I was going to study during my fellowship and started pursuing this.”

When the researchers blocked activity in the projection with the amber laser, the animals showed even more anxiety-like behavior than they usually do. The experiments hint at how the brain is able to regulate anxiety levels — on a millisecond timescale — by dialing activity up and down in such antagonistic amygdala pathways.

Futuristic anxiety treatment?

Tye said she and Deisseroth plan to follow up with further dissection of anxiety pathways. She also hopes to examine whether such optogenetic manipulations, sustained over hours or days, might induce long-lasting adaptations — perhaps for weeks –– in the set-points of anxiety pathways.

A future anxiety disorder treatment that might similarly target such specific pathways could, theoretically, quell anxiety instantly without producing unwanted side effects, such as drowsiness, often experienced with current anti-anxiety medications. For patients with severely debilitating anxiety, a treatment something like deep brain stimulation for depression, but more precisely targeted at a specific pathway, might someday be feasible, she suggested.

“Everything else in your brain should be unperturbed, because the manipulation would be so specific,” explained Tye.

Material adapted from NIMH.

Download the Video
Video Of A Mouse Under Optogenetic Control
Video shows a mouse under “optogenetic” control while in an anxiety-producing situation. Being in elevated, open spaces makes mice anxious. So, in this “elevated-plus maze,” the mouse normally stays in the arms with high walls; it normally won’t venture into arms with low walls. However, this mouse has been genetically engineered to have an anxiety-quelling pathway in its fear hub activate when a blue laser shines on it via the fiber-optic cable. At those times (when the blue text appears), the animal gains courage and ventures into the normally scary places. Video speeds up a 15 minute session 10-fold. Source, Kay M. Tye, Ph.D., Stanford University

Reference
Amygdala circuitry mediating reversible and bidirectional control of anxiety. Tye KM, Prakash R, Kim SY, Fenno LE, Grosenick L, Zarabi H, Thompson KR, Gradinaru V, Ramakrishnan C, Deisseroth K. Nature. 2011 Mar 17;471(7338):358-62. Epub 2011 Mar 9. PMID: 21389985

“If you misread facial expressions, you’re in social trouble, no matter what other social skills you have,” says Nowicki. “It can make life very difficult because other people’s faces are like a prism through which we look at the world.”

It is easy to assume that a socially anxious child would be especially sensitive to anger. “It turns out that they never learn to pick up on anger and often make the error of seeing it as sadness,” Nowicki says. “It sets up a very problematic interaction.”

Some socially anxious children long to interact with others, he says, and may try to comfort someone they think is sad, but who is actually angry. “They want to help, because they’re good kids,” Nowicki says. “I’ve seen these kids trying to make a friend, and keep trying, but they keep getting rebuffed and are never aware of the reason why.”

It is unclear whether misreading the facial expression is linked to the cause of the anxiety or merely contributing to it.

By identifying the patterns of errors in nonverbal communication, Nowicki hopes to create better diagnostic tools and interventions for those affected with a range of behavioral disorders.

For more than two decades, in association with Emory psychologist Marshall Duke, Nowicki has produced a groundbreaking body of work on how non-verbal communication impacts a child’s development. They have found that in a range of children with behavioral disorders, including high-functioning autism, direct teaching can improve their non-verbal communication.

“When I first started this work, people asked me, why are you doing this? Everybody can recognize emotions in faces,” Nowicki recalls. Nonverbal communication was not taken that seriously, and relegated to popular magazine articles like, “Seven ways to improve your body language.”

In his clinical practice, however, Nowicki noticed that some children who had trouble socializing appeared to misinterpret nonverbal clues. He sought ways to measure the deficits and remediate them.

“My heart went out to these kids,” he says. “I had the idea that nonverbal communication could be taught. It’s a skill, not something mysterious.”

Nowicki and Duke termed the coin “dyssemia,” meaning the inability to process signs. They also developed the Diagnostic Analysis of Nonverbal Accuracy (DANVA) to assess subtle cues to emotional expressions, including visual signals and tone and cadence of voice. DANVA is now widely used by researchers in studies of everything from emotionally disturbed children to the relationships between doctors and their patients.

Material adapted from Emory University.

A research team led by Karl Deisseroth, associate professor of psychiatry and behavioral sciences and bioengineering, identified two key pathways in the brain: one which promotes anxiety, and one which alleviates anxiety.

The pathways are in a brain region called the amygdala. Prior research suggests the amygdala plays a role in anxiety, but earlier studies used widespread modifications of the amygdala through drugs or physical disruption of the brain region to study the way in which it affects anxiety. This new work, published in this week’s Nature, uses a tool called optogenetics – developed by Deisseroth and recently named Method of the Year by Nature Methods – to specifically tease out which pathways contribute to anxiety.

Optogenetics combines genetics and optical science to selectively manipulate the way a neuron fires in the brain. Neurons are electrically excitable cells that convey information through electrical and chemical signaling.

Directed genetic manipulations cause specific neurons to assemble a light-activated protein normally found in algae and bacteria. When triggered by certain wavelengths of light, these proteins allow researchers to increase or decrease neuronal activity in the brain and observe the effects on rodent models in an experiment.

Using optogenetic manipulation of various amygdala pathways, Deisseroth and colleagues examined how mouse behavior was affected. Since mice display anxiety-related behaviors in open spaces, they measured changes in anxiety by analyzing how much time mice spent exploring the center of an open field or exploring the length of a platform without walls.

A new study supports the role of a brain region called the amygdala in processing anxiety. In this 3-D magnetic resonance imaging (MRI) rendering of a human brain, functional MRI (fMRI) activation of the amygdala is highlighted in red. Credit - NIMH Clinical Brain Disorders Branch

While optogenetics has been used to study amygdala function in behaviorally-conditioned fear, this is the first time it has been used to study anxiety. “Fear and anxiety are different,” Deisseroth explained. “Fear is a response to an immediate threat, but anxiety is a heightened state of apprehension with no immediate threat. They share the same outputs, for example physical manifestations such as increased heart rate, but their controls are very different.”

Anxiety disorders are the most prevalent among all psychiatric diseases, and include diseases such as post-traumatic stress disorder, obsessive-compulsive disorder, and phobias. Anxiety also contributes to other major psychiatric disorders such as depression and substance abuse.

“Now that we know that these cell projections [in the amygdala] exist, we can first use this knowledge to understand anxiety more than we do now,” Deisseroth noted.

Deisseroth has previously used optogenetics to study deep brain stimulation in Parkinson’s disease. This research was detailed last year in the journal Science and reported online by the National Science Foundation (NSF).

“Deep brain stimulation is increasingly being considered for psychiatric disorders, so after studying Parkinson’s disease, we started building towards research on psychiatric disorders,” Deisseroth commented. Next he wants to use these tools to study depression and autism spectrum disorders.

Material adapted from National Science Foundation.

Social anxiety is a common disorder, marked by overwhelming fears of interacting with others and expectations of being harshly judged. Medication and psychotherapy both help people with the disorder. But research on the neurological effects of psychotherapy has lagged far behind that on medication-induced changes in the brain.

“We wanted to track the brain changes while people were going through psychotherapy,” says McMaster University Ph.D. candidate Vladimir Miskovic, the study’s lead author.

To do so, the team – led by David Moscovitch of the University of Waterloo, collaborating with McMaster’s Louis Schmidt, Diane Santesso, and Randi McCabe; and Martin Antony of Ryerson University – used electroencephalograms, or EEGs, which measure brain electrical interactions in real time. They focused on the amount of “delta-beta coupling,” which elevates with rising anxiety.

The study recruited 25 adults with social anxiety disorder from a Hamilton, Ontario clinic. The patients participated in 12 weekly sessions of group cognitive behavior therapy – a structured method that helps people identify and challenge the thinking patterns that perpetuate their painful and self-destructive behaviors.

Two control groups that included students who tested extremely high or low for symptoms of social anxiety underwent no psychotherapy.

The patients were given four EEGs (two before treatment, one halfway through, and one two weeks after the final session). The researchers collected EEG measures of the participants at rest and then during a stressful exercise: a short preparation for an impromptu speech on a hot topic, such as capital punishment or same-sex marriage; participants were told the speech would be presented before two people and videotaped. In addition, comprehensive assessments were made of patients’ fear and anxiety.

When the patients’ pre- and post-therapy EEGs were compared with the control groups’, the results were revealing:  before therapy, the clinical group’s delta-beta correlations were similar to those of the high-anxiety control group and far higher than the low-anxiety group’s. Midway through, improvements in the patients’ brains paralleled clinicians’ and patients’ own reports of easing symptoms. And at the end, the patients’ tests resembled those of the low-anxiety control group.

“We can’t quite claim that psychotherapy is changing the brain,” cautions Miskovic. For one thing, some of the patients were taking medication, and that could confound the results. But the study, funded by the Ontario Mental Health Foundation, is “an important first step” in that direction and toward understanding the biology of anxiety and developing better treatments.

The work might also alter perceptions of therapy. “Laypeople tend to think that talk therapy is not ‘real,’ while they associate medications with hard science, and physiologic change,” says Miskovic. “But at the end of the day, the effectiveness of any program must be mediated by the brain and the nervous system. If the brain does not change, there won’t be a change in behavior or emotion.”

Material adapted from Association for Psychological Science.

Reference
“Changes in EEG Cross-Frequency Coupling During Cognitive Behavioral Therapy for Social Anxiety Disorder” will be released in an upcoming issue of the APS journal Psychological Science.

Background

Anxiety disorders are characterized by an excessive, irrational dread of everyday situations. Some people may experience general, chronic anxiety, while others become anxious in response to one or more specific triggers. Many studies have implicated two brain regions in anxiety – the amygdala in fear responses and the ventral prefrontal cortex (vPFC) in suppressing or regulating fear. Questions remain, however, about how trait anxiety – a person’s typical anxiety level on any given day – affects amygdala and vPFC functioning.

To explore these questions, Sonia Bishop, Ph.D., of the University of California Berkeley (at the University of Cambridge (UK) at the time of data collection), and colleagues designed a series of experiments to determine how the amygdala and vPFC responded in three types of situations:

• Cued fear – a neutral signal or cue is followed by an aversive event. In this study, the cue was an actor in a video placing his hands over his ears and the aversive event was a loud scream. The cue provided a reliable prediction of the aversive event. Cued fear can be compared to the situation-specific type of anxiety experienced by those with a specific phobia, such as a fear of heights.
• Contextual fear – a neutral cue and an aversive event occur independently of each other. The cue did not provide a reliable prediction of the aversive event. Contextual fear may be similar to the non-specific anxiety that affects people with generalized anxiety disorder.
• Safety – a neutral signal or cue occurs alone without an aversive event. The safety situation served as a comparison for the other two situations.

The researchers assessed the level of trait anxiety of 23 healthy study participants, ages 18 to 41. Each participant underwent a training session that exposed them to the above conditions. Two days after the training session, participants had their brain activity recorded through functional magenetic resonance imaging (fMRI), a noninvasive imaging method, while re-exposed to the cued fear, contextual fear, and safety conditions in the scanner.

Results from the Study

Participants with high trait anxiety showed greater amygdala response to cued fear situations compared to those with low trait anxiety. According to the researchers, this finding suggests that individual differences in amygdala response may contribute to differences in vulnerability to cue-specific anxiety disorders, such as specific phobia.

Participants with low trait anxiety showed increased vPFC activity in response to cued fear and more strongly sustained vPFC activity during contextual fear situations, compared to those with high trait anxiety. Notably, vPFC activity in participants with low trait anxiety occurred before the aversive event had ceased. The researchers suggest that this process – engaging brain areas that help to suppress fear even when the source of fear is still present – may help to protect against chronic anxiety disorders even when stressful life events are ongoing.

Significance

The study’s findings support a potential role of the amygdala in vulnerability to anxiety disorders and a potential role of the vPFC in protection against them.

“Individual differences in the functioning of one or both of these brain regions may help account for the variability in symptoms across different anxiety disorders,” said Bishop. “A better understanding of these processes may help inform treatment choice and predict treatment response.”

This study was supported in part by a Biobehavioral Research Award for Innovative New Scientists (BRAINS) from NIMH. Dr. Bishop was one of 12 researchers to receive this award in 2010.

Reference

Indovina I, Robbins TW, Núñez-Elizalde AO, Dunn BD, Bishop SJ. Fear-Conditioning Mechanisms Associated with Trait Vulnerability to Anxiety in Humans. Neuron. 2011 Feb 10;69(3):563-71.

The biological-behavioral treatment program is called Capnometry-Assisted Respiratory Training, or CART, said psychologist and panic disorder expert Alicia E. Meuret at Southern Methodist University in Dallas.

CART helps patients learn to breathe in such a way as to reverse hyperventilation, a highly uncomfortable state where the blood stream operates with abnormally low levels of carbon dioxide, said Meuret, one of the researchers conducting the study.

Hyperventilation, a state of excessive breathing, results from deep or rapid breathing and is common in patients with panic disorders. “We found that with CART it’s the therapeutic change in carbon dioxide that changes the panic symptoms – and not vice versa,” Meuret said.

CART: Breathing exercises twice a day
During the treatment, patients undergo simple breathing exercises twice a day. A portable capnometer device supplies feedback during the exercises on a patient’s CO2 levels. The goal of these exercises is to reduce chronic and acute hyperventilation and associated physical symptoms. This is achieved by breathing slower but most importantly more shallowly. Contrary to lay belief, taking deep breaths actually worsens hyperventilation and symptoms.

“Most panic-disorder patients report they are terrified of physical symptoms such as shortness of breath or dizziness,” Meuret said. “In our study, cognitive therapy didn’t change respiratory physiology, but CART did effectively reduce hyperventilation. CART was proved an effective and powerful treatment that reduces the panic by means of normalizing respiratory physiology.”

The findings, “Respiratory and cognitive mediators of treatment change in panic disorder: Evidence for intervention specificity,” appeared in the Journal of Consulting and Clinical Psychology. Meuret, who developed CART, is an assistant professor in the Department of Psychology at SMU and co-directs the department’s Stress, Anxiety and Chronic Disease Research Program. The Beth & Russell Siegelman Foundation funded the research.

CART breathing a proven biological therapy
The study pitted CART against a conventional cognitive therapy treatment, or CT. Traditional CT teaches patients techniques aimed at helping them change and reverse catastrophic thoughts in order to reduce fear and panic.

In the CART-CT study, 41 patients were assigned to complete either a CART or CT treatment program for panic disorder and agoraphobia, a fear of being trapped with no means of escape or help.

Both treatment programs were equally effective in reducing symptoms, said Meuret. But CART was the only treatment to physiologically alter panic symptoms by actively reversing hyperventilation in the patients. Cognitive therapy did not change the respiratory physiology, said Meuret.

Treatment helps patients address terror associated with panic
The study is the second randomized control trial to measure CART’s effectiveness. By reversing hyperventilation, patients reported a new ability to reduce panic symptoms by means of changing their respiration.

With CT, Meuret said, if a patient reports shortness of breath, the therapist challenges the assumption by asking how often the person actually has suffocated during a panic attack, then hopes that will reverse the patient’s thinking.

“I found that process very challenging for some of my patients because it acknowledges the symptom but says it’s not a problem,” Meuret said.

“CART, however, tells us a patient’s CO2 is very low and is causing many of the symptoms feared, but it can also show how to change these symptoms through correct breathing. There has been an assumption that if people worry less about symptoms it will also normalize their physiology, but this study shows that this is not the case,” she said. “Hyperventilation remains unchanged, which could be a risk factor for relapse down the road. Apart from hyperventilation being a symptom generator, it is an unhealthy biological state associated with negative health outcomes.”

Broader study planned to measure CART
The researchers plan to branch out with their studies on CART by taking the program into the community, particularly to ethnic minorities. They believe CART is a more universally understood treatment due to its physical exercises – as opposed to cognitive therapy’s more intellectual methods – and therefore more accessible to a broader range of people with varying levels of education and different cultural backgrounds. Ongoing studies will test the efficacy of CART in patients with asthma and fear of blood.

Material adapted from Southern Methodist University.

“These findings suggest that children with severe forms of congenital heart defects are prone to emotional problems at a very young age. The increased risk of anxiety could be related to the number of medical procedures and hospital admissions that characterise the first years of life for these children,” said PhD student Kim Stene-Larsen at the NIPH.

Part of the HEARTKIDS project

The NIPH is collaborating with the Department of Paediatric Cardiology at Oslo University Hospital on a major research project, HEARTKIDS.

In this follow-up study the researchers examined whether children with congenital heart defects had an increased risk of internalising problems such as anxiety or sleep problems at 18 months of age.

Out of 198 eighteen month old children with a congenital heart defect who were studied, 58 had a severe heart defect. Analysis showed that the children with a severe heart defect had a doubled risk of anxiety compared to healthy children.

In addition to the severity of the heart defect, maternal anxiety and depression explained some of the anxiety in these children. Children with mild or moderate heart defects, however, showed no signs of anxiety or other internalising problems.

The HEARTKIDS project is a sub-study of the Norwegian Mother and Child Cohort Study (MoBa). The project is funded by the Norwegian Research Council. This longitudinal study aims to explore the psychological and developmental consequences of congenital heart defects in infants and toddlers. Through a merge of the MoBa and the Oslo University Hospital’s nationwide register of congenital heart defects, which provides accurate diagnostic information about heart defects, it is possible to compare children with varying severity of heart defects with healthy children.

Previous findings from the HEARTKIDS project have shown that 6-month-old children with moderate or severe congenital heart defects show a higher risk of emotional reactivity (irritability, frequent and powerful crying).

Need for more knowledge about children with congenital heart defects

Approximately one percent of all newborn children have a congenital heart defect. The severity of the heart defects varies widely from minor defects to complex conditions that require a series of operations throughout the child’s first year.

Several studies have shown that children with congenital heart defects down to 3 years of age are more prone to emotional problems like anxiety and depression. However, there is little knowledge about the emotional problems in infancy and early childhood, which is the phase of life where most of the medical treatment is carried out. The HEARTKIDS project is focusing on the phase from birth to child age 3 years of age.

Material adapted from Norwegian Institute of Public Health.

Reference
Longitudinal findings from a Norwegian case-cohort study on internalising problems in children with congenital heart defects is published online by Acta Paediatrica. Doi: 10.1111/j.1651-2227.2010.02015.x.

The study enrolled 13 boys and 10 girls in this study, all of whom had been diagnosed with pediatric anxiety disorder. Their study showed that children and adolescents, ages 8 to16, who show fear when looking at happy faces on a screen inside an fMRI scanner were those who had least success with an eight-week course of CBT.

Conversely, children who showed fear while looking at fearful faces benefitted from the treatment, which is also known as talk therapy, the researchers found.

“Anxiety and fear are intrinsically linked, so how the brain’s fear center responds would naturally affect how anxiety disorders manifest,” says the study’s lead author, Steve Rich, a fourth year medical student.

“Indeed, the impact on their responses to therapy was impressive,” he says. “Past studies have shown that many people react to fearful faces with fear themselves, but our most robust finding indicated that some anxiety disorder patients have more anxiety towards happy faces than fearful ones, and those patients were the least likely to respond to cognitive behavioral therapy.”

While inside the fMRI machine, the participants were shown pictures of faces that expressed certain emotions strongly. “The questions we were trying to answer were: What emotions make people afraid when they witness them on others’ faces, and does that pattern predict response to talk therapy,” Rich says.

An fMRI is a type of scan that records changes in blood flow being used at each location in the brain, thus showing levels of activity. In this study, the researchers zeroed in on the amygdala, a brain structure known to represent the emotion of fear.

They then correlated the differing responses they saw in the amygdala with outcomes from an eight-week course in cognitive behavioral therapy.

The researchers found a significant correlation, indicating that pre-treatment fMRI can be used to select patients who likely do well with talk therapy alone, and those that may require other therapy, such as medication.

Rich says that one explanation for the results is that those patients who have greater anxiety towards happy faces than towards fearful ones have a subtly different disorder, one that is very similar but cannot be treated by cognitive behavioral therapy.

“In this subset of patients, that support may actually elicit even more anxiety, thus alienating them from the therapist,” he says. “Further study is required to determine whether this is indeed a unique disease subtype, or whether a modified approach to cognitive behavioral therapy that requires the therapist to stay completely neutral could make therapy more effective for these patients.”

Rich and his co-authors do not expect that every pediatric anxiety disorder patient should receive an fMRI diagnosis.

“fMRI is expensive, and this study does not by any means suggest that it should be used as a universal screening tool,” he says. “Even so, once the field develops further, our results suggest that neuroimaging studies like fMRI may be able to help us understand why a given patient might not be responding to the first-line treatment. In other words, when routine care is not enough, we can focus on the nuances of the individual.”

Support for this research was provided to Rich during a summer research fellowship at the National Institute of Mental Health.

Material adapted from Georgetown University Medical Center.

“Why this small group of neurons dies in Parkinson’s disease is the core question we struggled with,” says lead author D. James Surmeier, the Nathan Smith Davis Professor and chair of physiology at Northwestern University Feinberg School of Medicine. “Our research provides a potential answer by showing this small group of neurons uses a metabolically expensive strategy to do its job. This ‘lifestyle’ choice stresses the neurons’ mitochondria and elevates the production of superoxide and free radicals – molecules closely linked to aging, cellular dysfunction and death.”

The good news is preclinical research shows this stress can be controlled with a drug already approved for human use. By preventing calcium entry, the drug isradipine reduced the mitochondrial stress in dopamine-releasing neurons to the levels seen in neurons not affected by the disease.

Northwestern Medicine scientists currently are conducting a clinical trial to find out if isradipine can be used safely and is tolerated by patients with Parkinson’s. Isradipine is already approved by the Food and Drug Administration for treatment of high blood pressure.

Parkinson’s disease is the second most common neurodegenerative disease in the United States, second only to Alzheimer’s disease. The average age of diagnosis is near 60. More than 1 million Americans currently have Parkinson’s disease, and this number is rising as the population ages. The symptoms of Parkinson’s disease include rigidity, slowness of movement and tremors. No treatment currently is known to prevent or slow the progression of Parkinson’s disease.

Although most cases of Parkinson’s disease have no known genetic link, Surmeier’s study in mice showed that the mitochondrial stress in dopamine-releasing neurons was worsened in a genetic model of early-onset Parkinson’s disease, suggesting a similar mechanism in rare familial forms of the disease and the more common forms.

Everyone loses dopamine-releasing neurons with age, Surmeier noted. “By lowering their metabolic stress level, we should be able to make dopamine-releasing neurons live longer and delay the onset of Parkinson’s disease,” he said. “For individuals diagnosed with Parkinson’s disease, the hope is that this drug can slow disease progression, giving symptomatic therapies a broader window in which to work.”

Material adapted from Northwestern University.

While overall quit rates for the study were high, participants with anxiety diagnoses were much less likely to quit smoking.

Study results also showed that anxiety diagnoses were very common among participants — more than a third of them met criteria for at least one anxiety diagnosis in their lifetime. Out of all 1,504 study participants, 455 had had a panic attack in the past, 199 social anxiety disorder, and 99 generalized anxiety disorder (some reported having more than one diagnoses).

Other research has shown that up to 25 percent of the more than 50 million smokers in the U.S. had at least one anxiety disorder in their lifetime. And yet, very little research has addressed smoking in this population.

Lead author Megan Piper says it surprised her that the nicotine lozenge and patch – alone or in combination – failed to help patients with an anxiety history to quit smoking. In the general population, the lozenge and patch – especially when combined – have been very effective in helping patients quit smoking. Bupropion (Zyban) alone, or in combination with the nicotine lozenge, also did not increase cessation rates among patients with a history of anxiety disorders.

“Further research is needed to identify better counseling and medication treatments to help patients with anxiety disorders to quit smoking,” Piper says.

Smokers in the study with anxiety disorders also reported higher levels of nicotine dependence and withdrawal symptoms prior to quitting. Smokers often experience craving, negative feelings, and difficulty concentrating in the minutes or hours after finishing a cigarette, and those feelings can be heightened simply because the smokers know they are about to attempt to quit. In addition, participants with a history of panic attacks or social-anxiety disorder experienced more negative feelings on their quit day than did smokers in the study without this history.

These findings suggest that clinicians should assess anxiety-disorder status when helping patients quit smoking. While anxiety medications alone have not boosted cessation rates, Piper is planning further research to test other quit-smoking counseling interventions and medications with patients who have had an anxiety diagnosis.

In the meantime, all smokers can call the national tobacco quit line at 1-800-QUIT-NOW for free, confidential coaching and support to quit smoking.

Material adapted from University of Wisconsin-Madison.

The research was carried out by Shaheen Lakhan and Karen Vieira from the Global Neuroscience Initiative Foundation, a non-profit charity organization for the advancement of neurological and mental health patient welfare, education, and research, based in Los Angeles, USA. Lakhan said, “Our review and summary of the literature on herbal remedies and dietary supplements for anxiety should aid mental health practitioners in advising their patients and provide insight for future research in this field. We found mixed results – while passionflower or kava and L-lysine and L-arginine appeared to be effective, St John’s Wort and magnesium supplements were not”.

Of the studies included in the review, 21 were randomized controlled trials. Of these, 15 showed positive effects from either a nutritional or herbal remedy and any reported side effects were mild to moderate. According to Lakhan, “For all three of the herbal supplements we reviewed, more research needs to be done to establish the most effective dosage and to determine whether this varies between different types of anxiety or anxiety-related disorders. Herbal medicines hold an important place in the history of medicine as most of our current remedies, and the majority of those likely to be discovered in the future, will contain phytochemicals derived from plants”.

Material adapted from BioMed Central.

Download / Reference
Shaheen E Lakhan, & Karen F Vieira (2010). Nutritional and herbal supplements for anxiety and anxiety-related disorders: systematic review. Nutrition Journal, 9:42 (7 October 2010).

Methods
The participant sample consisted of 70 patients diagnosed with panic disorder. Logistic regression analysis was performed with EEG findings as dependent variables and age, sex and with or without the 13 symptoms as independent variables.

EEG Recording
For EEG record, Nihon Kohden EEG-1514 leads were attached to both earlobes (A1 and A2). The reference electrode was 12 channels: Fp1, Fp2, C3, C4, P3, P4, 01, 02, F7, F8, T3 and T4, according to the international 10-20 system of Electrode Placement, and the EEG was recorded for 15 consecutive minutes or more. The bipolar leads were 12 channels: Fp1-F3, Fp2-F4, F3-C3, F4-C4, C3-P3, C4-P4, P3-01, P4-02, Fp1-F7, Fp2-F8, F7-T3 and F8-T4, and the EEG was recorded for 2 consecutive minutes or more. Photic stimulation was given at 10 second intervals at 3, 5, 6, 8, 10, 12, 14, 15, 18, 20 and 24 Hz, and hyperventilation was carried out for 5 minutes at 3 second intervals.

Table 1: Characteristics of patients with panic disorder subclassified on the basis of EEG findings. (click to enlarge)

EEG Recording Interpretation Criteria
EEG record reading was based on the decision criteria of adult EEG proposed by Teruo Ohkuma in 1999, which are widely accepted in Japan. The criteria details are 1) EEG with eyes closed is composed of alpha or faster activity than alpha. Obvious theta and delta waves do not appear. 2) alpha waves and fast activity show normal localization. 3) There is no difference of 20-30% or more in the amplitude of symmetric parts. 4) There is no difference of 10% or more in the duration of symmetric parts. 5) alpha attenuation occurs with open eyes, sensory stimuli, and mental activities 6) Neither alpha nor fast activity show abnormally high amplitude. 7) No intermittent activities appear, such as spike waves or sharp waves (intermittent abnormal activity, epileptic pattern).

Table 2: EEG abnormal findings of 17 cases (click to enlarge)

Results
17 of the 70 participants evidenced EEG abnormalities. There were no significant difference with agoraphobia, psychiatric disorders, drinker, and smoker or not (Table 1). Of the 17 with EEG abnormalities, 13 had repeated slow waves in the theta-band – the most prevalent EEG abnormality found in this study. Paroxysmal abnormality interpreted as epileptiform was found in only two cases. Additionally, nausea or abdominal distress (37.7% vs 82.45%, OR-12.5), derealization or depersonalization (7.5% vs 47.1%, OR=13.9), and paresthesias (43.4% vs 64.7%, OR=7.9) were extracted by multivariate analysis as factors related to EEG abnormalities.

Conclusion
Of the 70 patients studied, 17 had EEG abnormalities. Among these 17 cases, “repeated slow waves in the theta-band” was the most common abnormality. Only two out of the 70 cases examined had epileptiform discharges. The factors identified as being related to EEG abnormalities are nausea or abdominal distress, derealization or depersonalization, and paresthesias. The study indicated that physiological predispositions symbolized in EEG abnormality are closely related to panic attacks.

Download/Material adapted from:
Hayashi, Karin and Makino, Mariko and Hashizume, Masahiro and Nakano, Koichi and Tsuboi, Koji (2010). EEG abnormalities in panic disorder patients: a study of symptom characteristics and pathology. BioPsychoSocial Medicine, 4, 1.

The study was developed by Antonia Pilar Pacheco-Unguetti, Alberto Acosta, Alicia Callejas and Juan Lupiáñez, from the department of Experimental Psychology and Behavioural Physiology of the University of Granada. It will be published in the next issue of the prestigious journal Psychological Science.

Two Types of Anxiety
There are two types of anxiety: trait anxiety, which is a quality of personality that indicates a tendency to feel anxiety and restlessness; and state anxiety, which is an emotional reaction raised in response to a stressful situation or context. However, the difference between trait and state anxiety has not been identified or established for decades on the grounds that both types of anxiety make individuals more receptive to negative information to the detriment of positive or neutral information.

The researchers from the University of Granada have evaluated whether these subtypes of anxiety affect attention differently. To the purpose of this study, an attention test prepared by the researchers was provided to some participants with high and low trait anxiety values and to other groups of students that had been previously induced to a high state of anxiety or to a positive emotional state.

The results revealed double dissociation in attentional performance. Cognitive control networks of participants with high trait anxiety values showed a deficient attentional performance. Cognitive control networks are responsible for conflict resolution and voluntary action control, functions which are related to the prefrontal cortex. Conversely, the participants with high state anxiety presented an overfunctioning of the alerting and orienting networks, which are attention networks more heavily influenced by the process of analysis of stimuli.

The results obtained provide first evidence that trait and state anxiety affect attention processes differently. Further, from these results, it can be concluded that such influence is present in situations where emotional information processing is not required. This dissociation may help develop specific therapies allowing patients with anxiety disorders to control themselves. The aim is to help patients reinforce efficient mechanisms to focus on the demands of the situation by inhibiting distracting information.

Material adapted from University of Granada by CFisher.

References:
Bishop, S.J. (2009). Trait anxiety and impoverished prefrontal control of attention. Nature Neuroscience, 12, 92-98.
Bishop, S.J., Jenkins, R., y Lawrence, A.D. (2007). Neural processing of fearful faces: Effects of anxiety are gated by perceptual capacity limitations. Cerebral Cortex, 17, 1595-1603.
Callejas, A., Lupiáñez, J., y Tudela, P. (2004). The three attentional networks: On their independence and interactions. Brain and Cognition, 54(3), 225-227.
Pacheco-Unguetti, A. P., Acosta, A., Callejas, A., y Lupiáñez, J. (en prensa). Attention and anxiety: Different attentional functioning under state and trait anxiety. Psychological Science.
Pacheco-Unguetti, A. P., Lupiáñez, J., y Acosta, A. (2009). Atención y ansiedad: relaciones de la alerta y el control con la ansiedad rasgo. Psicológica, 30, 1-25.
Posner, M. I., y Petersen, S. E. (1990). The attention system of the human brain. Annual Review of Neuroscience, 13, 25-42.

Published online in the journal Health Policy, the study by researchers at UBC’s Centre for Health Services and Policy Research (CHSPR) is the first of its kind to examine the use of benzodiazepines, such as Xanax and Ativan, for an entire population over time. It’s also the first to pinpoint the socio-economic characteristics associated with long-term users of such drugs.

Results show that seniors and low-income earners are more likely to be long-term users of benzodiazepines with rates remaining steady over a 10-year period. Meanwhile, use among the middle-aged population has increased. Harms associated with long-term use (more than 100 days in a year) can include dependence and tolerance, cognitive impairment, and increased risks of falls in the elderly.

“Given the potential for dependence and harms associated with these drugs, they are recommended to be used sparingly for short periods,” says Colleen Cunningham, CHSPR researcher and lead author of the study. “However, our study suggests that a significant number of British Columbians – especially the elderly who suffer greater health risks from falls – are using them for long periods.”

Benzodiazepines are one of the most commonly prescribed types of neurological drugs in developed countries. The UBC study compared health records of B.C. residents from 1996 and 2006. Of the 4.9 per cent of the overall B.C. population who were given short-term benzodiazepine prescriptions in 2006 and 3.5 per cent who were given long-term prescriptions:

• Nearly half of long-term users were over age 65, and more than a quarter were 75 or older
• Two out of three were women, both for short- and long-term use
• Long-term users were more likely to be in the lowest income bracket than short-term or non-users

Cunningham and co-authors Gillian Hanley and Steve Morgan found long-term use in 2006 was associated with early use – half of all 2006 long-term users had been prescribed benzodiazepines in 1996. The researchers are calling for prescribing practices and policies that target populations younger than conventionally studied (i.e. under age 65) to reduce rates of long-term use.

Material adapted from University of British Columbia by CFisher.

Background
Research has found that a collaborative care approach, in which one care manager coordinates a team of treatment providers, is effective in treating depression. However, research is limited on whether the same type of approach could work to treat anxiety disorders, which are commonly treated in primary care settings.

In response, Peter Roy-Byrne, M.D., of the University of Washington Seattle, and colleagues designed a flexible collaborative treatment model for anxiety disorders – Coordinated Anxiety Learning and Management (CALM) – and compared it to usual care. CALM included cognitive behavioral therapy (CBT) that was tailored to any one of four anxiety disorders – panic disorder, generalized anxiety disorder, social anxiety disorder or post traumatic stress disorder. It also included strategies to improve medication delivery and adherence. Of the 1,004 participants recruited from 17 primary care clinics in four U.S. cities, half were randomized to CALM and were allowed to choose whether they received CBT, medication, or both. The other participants were referred to usual care which could include medication, brief counseling with a physician, or referral to a mental health specialist. All participants were diagnosed with at least one of the four anxiety disorders addressed in the CBT program.

CALM participants received their initial treatment for 10 to 12 weeks. Those who still had symptoms after 12 weeks could receive additional CBT or medication, or both. They then received monthly follow-up phone calls to reinforce CBT skills or medication management advice for up to a year.

CALM relied on a computerized program to help train care managers in CBT techniques and ensure consistency of care. The computer program employed CBT principles common to all anxiety disorders, but included specific techniques designed to address the four anxiety disorders in the study, thus allowing for personalized treatment.

Care managers also encouraged participants to stay in treatment and monitored their reactions to medication, relaying any observations and suggestions for changes to the primary care provider. CALM tracked participants’ progress and outcomes through a web-based monitoring system as well.

Results of the Study
Participants in the CALM group showed significantly greater symptom improvement than those receiving usual care. After 12 months, about 63.6 percent receiving CALM had responded to treatment compared to 44.7 percent in usual care, and 51.5 percent receiving CALM had remitted compared to 33 percent in usual care.

CBT appeared to be the most popular treatment choice among those in the CALM group—57 percent chose CBT and medication combination treatment, and 34 percent chose CBT-only treatment, while 9 percent chose medication-only treatment. This preference is consistent with research that finds those with anxiety disorders tend to favor psychosocial treatment approaches over medication to treat their illness, said the researchers.

Significance
Because CALM included flexible treatment options, targeted multiple anxiety disorders, and was effective across a range of patients and clinics, it is broadly applicable in primary care settings. It could serve as a model for developing effective collaborative care of people with anxiety disorders as well as those with coexisting psychiatric disorders like depression, a situation commonly found in clinical settings.

What’s Next
Research is needed to determine how the strategy could best be implemented in primary care settings. In addition, a cost analysis of CALM is needed to determine whether it is a financially feasible option for payers and clinical settings.

Material adapted from National Institute of Mental Health by CFisher.

Reference
Roy-Byrne P, Craske MG, Sullivan G, Rose RD, Edlund MJ, Lang AJ, Bystritsky A, Welch SS, Chavira DA, Golinelli D, Campbell-Sills, L, Sherbourne CD, Stein MB. Delivery of evidence-based treatment for multiple anxiety disorders in primary care: a randomized controlled trial. Journal of the American Medical Association. 19 May 2010. 303(19).

Background (continued)
There is some evidence that numerous somatic symptoms or illness worry may be associated with impairment and high health care utilization [3, 6-14]. However, most studies have used self-report questionnaires and/or layman interviews which does not allow for the establishment of clinical diagnoses. Also, with a few exceptions, the studies are retrospective in design and comorbidity with other mental or physical disorders has not been taken into account. The authors were also not aware of any longitudinal studies on health care costs or self-rated health that followed up patients with a Hypochondriasis diagnosis according to Diagnostic and Statistical Manual (DSM-IV) or International Classification of Diseases (ICD-10). Relatively little is thus known about Hypochondriasis’ impact on self-rated functioning related to mental and physical health and longitudinal outcome [15-17].

Methodology
1785 consecutive primary care patients aged 18–65 who were consulting with their family physicians for a new illness were followed-up for two years in this randomized controlled trial (RCT). All patients filled in a screening questionnaire in the waiting room. This questionnaire included, among others, the eight-item version of the Symptom Check List (SCL-8d) [22], [23] that assesses anxiety and depression, the seven-item Whiteley scale [24] that measures worry and conviction of illness, the somatization subscale of the SCL-90 (SCL-SOM) that checks for 12 common physical symptoms [25], and the Cutting down, Annoyance by Criticism, Guilty feeling, Eye Openers Questionnaire (CAGE) that screens for alcohol abuse [26]. The patients also filled in the Medical Outcome Study’s Short Form (SF-36) [27]. A stratified subsample of 701 patients was assessed by the Schedules for Clinical Assessment in Neuropsychiatry interview. Patients with Hypochondriasis according to the DSM-IV (N = 59) and with mild (N = 21) and severe Health Anxiety (N = 81) were compared to a control group of patients who had a well-defined medical condition according to their family physician and a low score on the screening questionnaire (N = 968). Self-rated health was measured by questionnaire at baseline and at 3, 12, and 24 months, and health care use was extracted from patient registers.

Principal Findings
The 81 severe Health Anxiety patients and the 59 DSM-IV Hypochondriasis patients continued during follow-up to manifest significantly more Health Anxiety (Whiteley-7 scale) when compared with the 968 patients with well-defined medical conditions. They also continued to have significantly worse self-rated functioning related to physical and mental health (component scores of the SF-36). The severe Health Anxiety patients used a total of about 41–78% more health care per year, both during the 3 years preceding inclusion and during follow-up, whereas the DSM-IV Hypochondriasis patients did not have statistically significantly higher total use. A poor outcome of Health Anxiety was not explained by comorbid depression, anxiety disorder, or well-defined medical condition. Patients with mild Health Anxiety did not have a worse outcome on physical health and incurred significantly less health care costs than the group of patients with a well-defined medical condition.

Conclusions/Significance
This study suggests that severe Health Anxiety has significant long-term impact on the patients’ self-rated functioning related to mental and physical health and on health care costs, and the patients persistently report high levels of Health Anxiety measured on Whiteley-7. Health anxiety in its mild form, however, seems not to have any significant negative impact on physical health and health care costs. In addition, this study supports the validity of recently introduced new criteria for Health Anxiety.

Citation:
Material adapted By CFisher from:

Fink P, Ørnbøl E, Christensen KS (2010). The Outcome of Health Anxiety in Primary Care. A Two-Year Follow-up Study on Health Care Costs and Self-Rated Health. PLoS ONE 5(3): e9873. doi:10.1371/journal.pone.0009873

References:
Please see the original open access article for the extensive reference list. Numbered references in this current article match the references in the original article.

Lead study author, Rosalind J. Wright, MD, MPH, of the Channing Laboratory at BWH, says previous studies have suggested that a mother’s stress during pregnancy may influence the offspring’s immune system starting in the womb. In this study, researchers investigated differences in immune function markers in cord blood of infants born to mothers in high stress environments and those born to mothers with lower stress. They found that the patterns of cytokines related to certain stimulants differed based on the level of stress mothers reported.

“The cytokine patterns seen in the higher stress groups, which are an indication of how the child’s immune system is functioning at birth, may be a marker of increased risk for developing asthma and allergy as they get older,” explained Dr. Wright.

The researchers recruited pregnant women from urban areas. The families were largely ethnic minorities, with 20 percent living below the poverty level, and the father or pregnant mother having a history of asthma or allergy. The 557 families answered detailed questions about the various stressors in their lives, at home (including domestic violence), in their financial lives and in their neighborhoods (community violence). When the infants were born, their cord blood was collected; isolated immune cells were stimulated with a number of factors (allergens like dust and cockroach, viral and bacterial stimulants) and then analyzed for the production of various cytokines as indicators of how the child’s immune system was primed to respond to the environment.

“Current findings suggest that psychological stress is involved in programming of the infant immune response and that this influence begins during pregnancy,” said Dr. Wright. “As these infants mature, we will learn how these factors manifest later in terms of the development of asthma and allergy.

Material adapted from Brigham and Women’s Hospital by CFisher.

Dr. Alon Chen of the Weizmann Institute’s Neurobiology Department and his research team have now discovered that changes in the activity of a single gene in the brain not only cause mice to exhibit anxious behavior, but also lead to metabolic changes that cause the mice to develop symptoms associated with type 2 diabetes. These findings were published online this week in the Proceedings of the National Academy of Sciences (PNAS).

All of the body’s systems are involved in the stress response, which evolved to deal with threats and danger. Behavioral changes tied to stress include heightened anxiety and concentration, while other changes in the body include heat-generation, changes the metabolism of various substances and even changes in food preferences. What ties all of these things together? The Weizmann team suspected that a protein known as Urocortin-3 (Ucn3) was involved. This protein is produced in certain brain cells — especially in times of stress — and it’s known to play a role in regulating the body’s stress response. These nerve cells have extensions that act as ‘highways’ that speed Ucn3 on to two other sites in the brain: One, in the hypothalamus – the brain’s center for hormonal regulation of basic bodily functions — oversees, among other things, substance exchange and feelings of hunger and satiety; the other is involved in regulating behavior, including levels of anxiety. Nerve cells in both these areas have special receptors for Ucn3 on their surfaces, and the protein binds to these receptors to initiate the stress response.

The researchers developed a new, finely-tuned method for influencing the activity of a single gene in one area in the brain, using it to increase the amounts of Ucn3 produced in just that location. They found that heightened levels of the protein produced two different effects: The mice’s anxiety-related behavior increased, and their bodies underwent metabolic changes, as well. With excess Ucn3, their bodies burned more sugar and fewer fatty acids, and their metabolic rate sped up. These mice began to show signs of the first stages of type 2 diabetes: A drop in muscle sensitivity to insulin delayed sugar uptake by the cells, resulting in raised sugar levels in the blood. Their pancreas then produced extra insulin to make up for the perceived ‘deficit.’

‘We showed that the actions of single gene in just one part of the brain can have profound effects on the metabolism of the whole body,’ says Chen. This mechanism, which appears to be a ‘smoking gun’ tying stress levels to metabolic disease, might, in the future, point the way toward the treatment or prevention of a number of stress-related diseases.

Material adapted from Weizmann Institute of Science by CFisher.

The study also reveals a small molecule inhibitor developed by Ferguson, which may provide a new and better way to treat anxiety, depression, and other related disorders. The findings are published online in the journal Nature Neuroscience.

Ferguson, Ana Magalhaes and their colleagues used a behavioral mouse model and a series of molecular experiments to reveal the connection pathway and to test the new inhibitor. “Our findings suggest there may be an entire new generation drugs and drug targets that can be used to selectively target depression, and therefore treat it more effectively, ” says Ferguson, the director of the Molecular Brain Research Group at Robarts, and a professor in the Department of Physiology & Pharmacology at Western’s Schulich School of Medicine & Dentistry. “We’ve gone from mechanism to mouse, and the next step is to see whether or not we can take the inhibitor we developed, and turn it into a pharmaceutical agent.”

The research was conducted in collaboration with Hymie Anisman at Carleton University, and funded through the Canadian Institutes of Health Research (CIHR). “According to the World Health Organization, depression, anxiety and other related mood disorders now share the dubious distinction of being the most prevalent causes of chronic illness,” says Anthony Phillips, the scientific director of the CIHR Institute of Neurosciences, Mental Health and Addiction. “Using the power of molecular biology, Stephen Ferguson and colleagues provide novel insights that may be the key to improving the lives of so many individuals coping with these forms of mental ill health.”

The linking mechanism in the study involves the interaction between corticotropin releasing factor receptor 1 (CRFR1) and specific types of serotonin receptors (5-HTRs). While no one has been able to connect these two receptors on a molecular level, the study reveals that CRFR1 works to increase the number of 5-HTRs on cell surfaces in the brain, which can cause abnormal brain signaling. Since CRFR1 activation leads to anxiety in response to stress, and 5-HTRs lead to depression, the research shows how stress, anxiety and depression pathways connect through distinct processes in the brain. Most importantly, the inhibitor developed by the Ferguson lab blocks 5-HTRs in the pathway to combat anxious behaviour, and potentially depression, in mice.

While major depressive disorder often occurs together with anxiety disorder in patients, the causes for both are strongly linked to stressful experiences. Stressful experiences can also make the symptoms of anxiety and depression more severe. By discovering and then blocking a pathway responsible for the link between stress, anxiety and depression, Ferguson not only provides the first biological evidence for a connection, but he also pioneers the development of a potential drug for more effective treatment.

Video Interview
Visit this link to watch a video interview with the researcher.

Material adapted from University of Western Ontario by CFisher.

Reporting in the April edition of the Journal of the American Academy of Child and Adolescent Psychiatry, UCLA assistant professor of psychiatry Dr. Patricia Lester and her colleagues found that it is the number and length of repeated deployments that cause higher levels of anxiety in children and that this anxiety persists even after the deployed parent returns home.

Second, they found that the level of anxiety children experience can be predicted by the amount of psychological distress shown by both the active-duty parent and the at-home parent.

Lester and her colleagues studied 171 families in which either the mother or father was on active duty, currently deployed or recently returned from serving in Iraq or Afghanistan. Of the sample, the active-duty parent had, on average, been deployed more than twice and had been away from home for 16 months.

The researchers found that approximately one-third of the children in these families had increased symptoms of anxiety. Strikingly, the anxiety remained even after the deployed parent returned home.

“It’s known that, in general, a child’s level of distress is linked to parental distress,” Lester said. “Here, we found that approximately one-third of the at-home parents and almost 40 percent of the recently returned deployed parents showed elevations in anxiety and depression.

“We also found that the at-home parent showed higher levels of anxiety when their spouse was deployed. But the two key markers for anxiety in the child were the distress levels of both parents and the number of months a parent had been deployed during the child’s lifetime.”

Interestingly, the study suggests that school-aged boys and girls behave differently during and after a parent’s deployment. Girls showed an increase in acting out and disruptive behavior when the parent was deployed, while boys appeared to have more difficulties after the deployed parent returned.

“For the boys, this may be related to reduced autonomy and increased structure in the family life upon the return of the deployed parent,” Lester said.

Notably, the children also showed indices of resilience, and their experiences of other types of emotional and behavioral problems were comparable to what is seen normally within any general community of kids.

Lester noted that the military demographic in the U.S. has changed in the past several decades to include a much larger proportion of service members with families. She said planning is needed for extended military operations to take into account the impact on family members.

“These findings suggest that there is a cumulative wear and tear upon the military family from multiple deployments during wartime,” she said.

Lester and her colleagues have developed a program to help such military families. Called FOCUS (Families OverComing Under Stress), the program provides both parents and children customized training that addresses the impact of wartime deployment on families and helps them learn very specific communication and problem-solving skills to address these challenges.

Other authors on the study included Dorie Glover, Catherine Mogil, William Saltzman, Robert Pynoos and Katherine Wilt of UCLA; Kris Peterson and Larry Knauss of the Madigan Army Medical Center; James Reeves of the Naval Medical Center San Diego; Naihua Duan of Columbia University; and William Beardslee of Children’s Hospital Boston and Harvard Medical School.

The study was supported by a grant from the National Institute for Child and Human Development. The authors express no conflicts of interest.

Material adapted from UCLA by CFisher.

Experiments have found that the brains of mice with an inadequate amount of this protein, called brain-derived neurotrophic factor (BDNF), look similar to those of normal mice that have been under stress for long periods.

The experiments homed in on the gene for a protein that, among other things, enhances the adaptability of neurons in the hippocampus, a brain region that plays a key role in mood, cognition and memory. When normal mice are exposed to chronic stress (simulated by confinement in a wire mesh restraint), there is a significant retraction in the projections, or dendrites, of some of the neurons in the hippocampus, which shrinks in overall volume as well. The new experiments, reported recently in Hippocampus, looked at mice that had only one instead of the usual two copies of the gene that produces BDNF. The researchers, from Rockefeller University and Weill Cornell Medical College, found that these mice had brains resembling those of normal mice after extended stress. In other words, stress did not have any effect on the experimental mice.

Reduced reach. Tracings of neurons from mice with different levels of BDNF show that a short supply of the protein causes relatively shrunken neurons (right) in some parts of the hippocampus.

“The findings suggest that BDNF is one of the proteins that play a role in mediating the brain’s plasticity,” says Bruce S. McEwen, head of Rockefeller’s Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology.

If researchers can find a way to deplete or supplement BDNF in adult mice, they may be able to answer the question of when in development, or even in adult life, it has the greatest impact. “What we’re seeing is that there may be a developmental window for BDNF’s role, or also that there may be a floor and a ceiling for the right amount of the protein that helps enable adaptive plasticity,” McEwen says.

The new work adds to the understanding of BDNF’s interaction with hormones in the brain. McEwen’s lab recently discovered that a variant of the BDNF gene is a likely contender for a role in premenstrual disorders, changing mice’s performance on certain memory tasks according to their stage of the estrous cycle.

Material adapted from Rockefeller University by CFisher.

Reference
A.M. Magariños, C.J. Li, J. Gal Toth, K.G. Bath, D. Jing, F.S. Lee and B.S. McEwen. Effect of brain-derived neurotrophic factor haploinsufficiency on stress-induced remodeling of hippocampal neurons. Hippocampus online: January 21, 2010.

“We were surprised to find that the benefits of massage were no greater than those of the same number of sessions of ‘thermotherapy’ or listening to relaxing music,” said Karen J. Sherman, PhD, MPH, a senior investigator at Group Health Research Institute. “This suggests that the benefits of massage may be due to a generalized relaxation response.”

Massage therapy is among the most popular complementary and alternative medical (CAM) treatments for anxiety, she added. But this is the first rigorous trial to assess how effective massage is for patients with generalized anxiety disorder.

The trial randomly assigned 68 Group Health patients with generalized anxiety disorder to 10 one-hour sessions in pleasant, relaxing environments, each presided over by a licensed massage therapists who delivered either massage or one of two control treatments: Relaxation therapy: breathing deeply while lying down; or Thermotherapy: having arms and legs wrapped intermittently with heating pads and warm towels

All three treatments were provided while lying down on a massage table in a softly lighted room with quiet music. All participants received a handout on practicing deep breathing daily at home. Unlike the two control treatments, massage was specifically designed to enhance the function of the parasympathetic nervous system and relieve symptoms of anxiety including muscle tension.

Using a standard rating scale in interviews, the researchers asked the patients about the psychological and physical effects of their anxiety right after the 12-week treatment period ended and three months later, Dr. Sherman said.

All three of the groups reported that their symptoms of anxiety had decreased by about 40 percent by the end of treatment – and by about 50 percent three months later. In addition to the decline in anxiety, the patients also reported fewer symptoms of depression and less worry and disability. The research team detected no differences among the three groups; but the trial did not include a control group that got no treatment at all.

“Treatment in a relaxing room is much less expensive than the other treatments (massage or thermotherapy), so it might be the most cost-effective option for people with generalized anxiety disorder who want to try a relaxation-oriented complementary medicine therapy,” Dr. Sherman said.

Material adapted from Group Health Cooperative Center for Health Studies by CFisher.

“Our findings add to the growing body of evidence that physical activities such as walking or weight lifting may turn out to be the best medicine that physicians can prescribe to help their patients feel less anxious,” said lead author Matthew Herring, a doctoral student in the department of kinesiology, part of the UGA College of Education.

Herring pointed out that while the role of exercise in alleviating symptoms of depression has been well studied, the impact of regular exercise on anxiety symptoms has received less attention. The number of people living with chronic medical conditions is likely to increase as the population ages, he added, underscoring the need for a low-cost, effective treatment.

The researchers limited their analysis to randomized controlled trials, which are the gold standard of clinical research, to ensure that only the highest quality data were used. The patients in the studies suffered from a variety of conditions, including heart disease, multiple sclerosis, cancer, and chronic pain from arthritis. In 90 percent of the studies examined, the patients randomly assigned to exercise had fewer anxiety symptoms, such as feelings of worry, apprehension, and nervousness, than the control group.

“We found that exercise seems to work with just about everybody under most situations,” said study co-author Pat O’Connor, professor and co-director of the UGA Exercise Psychology Laboratory. “Exercise even helps people who are not very anxious to begin with become more calm.”

Exercise sessions greater than 30 minutes were better at reducing anxiety than sessions of less than 30 minutes, the researchers found. But surprisingly, programs with a duration of between three and twelve weeks appear to be more effective at reducing anxiety than those lasting more than 12 weeks. The researchers noted that study participants were less likely to stick with the longer exercise programs, which suggests that better participation rates result in greater reductions in anxiety.

“Because not all study participants completed every exercise session, the effect of exercise on anxiety reported in our study may be underestimated,” said study co-author Rod Dishman, also a professor of kinesiology. “Regardless, our work supports the use of exercise to treat a variety of physical and mental health conditions, with less risk of adverse events than medication.”

Material adapted from University of Georgia by CFisher.