Meditation and Stress

via derek bownds Davidson and McEwen offer a nice review of stress induced changes in the amygdala and hippocampus, and also describe experiments showing that mindfulness meditation can decrease both stress behavior and amygdala size. Here is their abstract, followed by two figures from the paper: Experiential factors shape the neural circuits underlying social and emotional behavior from the prenatal period to the end of life. These factors include both incidental influences, such as early adversity, and intentional influences that can be produced in humans through specific interventions designed to promote prosocial behavior and well-being. Here we review important extant evidence in animal models and humans. Although the precise mechanisms of plasticity are still not fully understood, moderate to severe stress appears to increase the growth of several sectors of the amygdala, whereas the effects in the hippocampus and prefrontal cortex tend to be opposite. Structural and functional changes in the brain have been observed with cognitive therapy and certain forms of meditation and lead to the suggestion that well-being and other prosocial characteristics might be enhanced through training. Figure - Chronic stress causes neurons to shrink or grow, but not necessarily to die. Representation of the chronic stress effects detected in animal models on growth or retraction of dendrites in the basolateral amygdala and orbitofrontal cortex (growth) and in the CA3 hippocampus, dentate gyrus and medial prefrontal cortex (shrinkage). These effects are largely reversible in young adult animals, although aging appears to compromise resilience and medial prefrontal cortex recovery. Figure - Change in gray matter volume in the right basolateral amygdala from pre to post 8 weeks of mindfulness based stress reduction was associated with decreases in perceived stress over this same time period (see Hölzel et al.). Individuals undergoing MBSR who showed the largest decreases in perceived stress also showed the largest decreases in basolateral amygdala gray matter volume.

Changing Brains

Changing brains for the better: Article documents benefits of multiple practices University of Wisconsin at Madison | April 18, 2012 | Cognition / 1 share digg redditstumblefark Practices like physical exercise, certain forms of psychological counseling and meditation can all change brains for the better, and these changes can be measured with the tools of modern neuroscience, according to a review article now online at Nature Neuroscience. The study reflects a major transition in the focus of neuroscience from disease to well being, says first author Richard Davidson, professor of psychology at University of Wisconsin-Madison. The brain is constantly changing in response to environmental factors, he says, and the article “reflects one of the first efforts to apply this conceptual framework to techniques to enhance qualities that we have not thought of as skills, like well-being. Modern neuroscience research leads to the inevitable conclusion that we can actually enhance well-being by training that induces neuroplastic changes in the brain.” “Neuroplastic” changes affect the number, function and interconnections of cells in the brain, usually due to external factors. Although the positive practices reviewed in the article were not designed using the tools and theories of modern neuroscience, “these are practices which cultivate new connections in the brain and enhance the function of neural networks that support aspects of pro-social behavior, including empathy, altruism, kindness,” says Davidson, who directs the Center for Investigating Healthy Minds at UW-Madison. The review, co-written with Bruce McEwen of Rockefeller University, begins by considering how social stressors can harm the brain. The massive neglect of children in orphanages in Romania did not just have psychological impacts; it created measurable changes in their brains, Davidson says. “Such studies provide an important foundation for understanding the opposite effects of interventions designed to promote wellbeing.” Davidson says his work has been shaped by his association with the Dalai Lama, who asked him in the 1990s, “Why can’t we use the same rigorous tools of neuroscience to investigate kindness, compassion and wellbeing?” Davidson, who has explored the neurological benefits of meditation, says, “meditation is one of many different techniques, and not necessarily the best for all people. Cognitive therapy, developed in modern psychology, is one of most empirically validated treatments for depression and counteracting the effects of stress.” Overall, Davidson says, the goal is “to use what we know about the brain to fine-tune interventions that will improve well-being, kindness, altruism. Perhaps we can develop more targeted, focused interventions that take advantage of the mechanisms of neuroplasticity to induce specific changes in specific brain circuits.” Brains change all the time, Davidson emphasizes. “You cannot learn or retain information without a change in the brain. We all know implicitly that in order to develop expertise in any complex domain, to become an accomplished musician or athlete, requires practice, and that causes new connections to form in the brain. In extreme cases, specific parts of the brain enlarge or contract in response to our experience.” Scientific documentation for the benefits of brain training may have broader social impacts, says Davidson. “If you go back to the 1950s, the majority of middle-class citizens in Western countries did not regularly engage in physical exercise. It was because of scientific research that established the importance of physical exercise in promoting health and well-being that more people now engage in regular physical exercise. I think mental exercise will be regarded in a similar way 20 years from now. “Rather than think of the brain as a static organ, or one that just degenerates with age, it’s better understood as an organ that is constantly reshaping itself, is being continuously influenced, wittingly or not, by the forces around us,” says Davidson, author of the new book “The Emotional Life of Your Brain.” “We can take responsibility for our own brains. They are not pawns to external influences; we can be more pro-active in shaping the positive

Blood tests and depression

First blood test to diagnose major depression in teens Tue Apr 17, 2012 17:41 from RSS 2.0 by Northwestern University A Northwestern Medicine scientist has developed the first blood test to diagnose major depression in teens, a breakthrough approach that allows an objective diagnosis by measuring a specific set of genetic markers found in a patient’s blood. The current method of diagnosing depression is subjective. It relies on the patient’s ability to recount his symptoms and the physician’s ability and training to interpret them. Diagnosing teens is an urgent concern because they are highly vulnerable to depression and difficult to accurately diagnose due to normal mood changes during this age period. The test also is the first to identify subtypes of depression. It distinguished between teens with major depression and those with major depression combined with anxiety disorder. This is the first evidence that it’s possible to diagnose subtypes of depression from blood, raising the hope for tailoring care to the different types. “Right now depression is treated with a blunt instrument,” said Eva Redei, a professor of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine and lead investigator of the study, published in Translational Psychiatry. “It’s like treating type 1 diabetes and type 2 diabetes exactly the same way. We need to do better for these kids.” “This is the first significant step for us to understand which treatment will be most effective for an individual patient,” added Redei, also the David Lawrence Stein Professor of Psychiatric Diseases Affecting Children and Adolescents. “Without an objective diagnosis, it’s very difficult to make that assessment. The early diagnosis and specific classification of early major depression could lead to a larger repertoire of more effective treatments and enhanced individualized care.” The estimated rates of major depressive disorder jump from 2 to 4 percent in pre-adolescent children to 10 to 20 percent by late adolescence. Early onset of major depression in teens has a poorer prognosis than when it starts in adulthood. Untreated teens with this disease experience increases in substance abuse, social maladjustment, physical illness and suicide. Their normal development is derailed, and the disease persists into adulthood. The depressed teens in the study were patients of Kathleen Pajer, M.D., a co-first author of the study, and her colleagues from the Research Institute of Nationwide Children’s Hospital in Columbus, Ohio. Pajer is now head of Dalhousie University’s division of child and adolescent psychiatry in Nova Scotia, Canada. The study subjects included 14 adolescents with major depression who had not been clinically treated and 14 non-depressed adolescents, all between 15 to 19 years old. The depressed and control subjects were matched by sex and race. Redei’s lab tested the adolescents’ blood for 26 genetic blood markers she had identified in previous research. She discovered 11 of the markers were able to differentiate between depressed and non-depressed adolescents. In addition, 18 of the 26 markers distinguished between patients that had only major depression and those who had major depression combined with anxiety disorder. The blood analysis was done by Brian Andrus from Redei’s lab, the other co-first author of the study, who was blind to the diagnoses of the subjects. “These 11 genes are probably the tip of the iceberg because depression is a complex illness,” Redei said. “But it’s an entree into a much bigger phenomenon that has to be explored. It clearly indicates we can diagnose from blood and create a blood diagnosis test for depression.” Redei first isolated and identified the genetic blood markers for depression and anxiety based on decades of research with severely depressed and anxious rats. The rats mirror many behavioral and physiological abnormalities found in patients with major depression and anxiety. Further indicating the challenge in working with depressed adolescents, none of the teens who were diagnosed with depression opted for treatment. “Everybody, including parents, are wary of treatment, and there remains a social stigma around depression, which in the peer-pressured world of teenagers is even more devastating,” Redei said. “Once you can objectively diagnose depression as you would hypertension or diabetes, the stigma will likely disappear.”

Monkey Fairness Video

De Waal on Fairness with Monkey Video http://www.ted.com/talks/frans_de_waal_do_animals_have_morals.html

Status and Health

Misery index Low social status is bad for your health. Biologists are starting to understand why Apr 14th 2012 | from the Economist ONCE upon a time the overstressed executive bellowing orders into a telephone, cancelling meetings, staying late at the office and dying of a heart attack was a stereotype of modernity. That was before the Whitehall studies, a series of investigations of British civil servants begun in the 1960s. These studies found that the truth is precisely the opposite. Those at the top of the pecking order actually have the least stressful and most healthy lives. Cardiac arrest—and, indeed, early death from any cause—is the prerogative of underlings. Such results have since been confirmed many times, both in human societies and in other primate species with strong social hierarchies. But whereas the pattern is well-understood, the biological mechanisms underlying it are not. A study just published in the Proceedings of the National Academy of Sciences, however, sheds some light on the matter. In this section »Misery index Little and not often, please To dye for Fun run Reprints In it, a group of researchers led by Jenny Tung and Yoav Gilad at the University of Chicago looked at the effects of status on rhesus macaques. Experience has shown that these monkeys display the simian equivalent of the Whitehall studies’ findings. The high risk of disease among those at the bottom of the heap in both cases suggests that biochemical responses to low status affect a creature’s immune system. Those responses must, in turn, depend on changes in the way the creatures’ genes are expressed. To investigate this phenomenon means manipulating social hierarchies, but that would be hard (and probably unethical) if it were done to human beings. You can, however, do it to monkeys, and the researchers did. Unhappy minds in unhealthy bodies Dr Tung and Dr Gilad took 49 middle-ranking female macaques (females were chosen because a lot of previous work on animal hierarchies has been done on female macaques) and split them into groups of four or five. The researchers were able to control where in a group an individual ranked by the order in which it was introduced into its group (newly introduced monkeys almost always adopt a role subordinate to existing group members). The hierarchies thus established, the team conducted tests on cells in the monkeys’ blood, in an attempt to determine the effect of a macaque’s rank on her biochemistry and, in particular, on how rank influences the activity of various genes. The answer is, a lot. Dr Tung and Dr Gilad looked at the expression in each animal of 6,097 genes (30% of the total number in a monkey genome—or, for that matter, in a human one). They were searching for correlations between social rank and gene activity, and in 987 genes they found one. Some genes were more active in high-ranking individuals; others were more active in low-ranking ones. The relationship was robust enough to work the other way round, too. Given a blood sample and no other information, it was possible to predict an individual’s status within her group with an accuracy of 80%. The next question was what all these genes actually do. Sure enough the answer, for a substantial fraction of them, was that they regulate aspects of the immune system. In particular, low-status individuals showed high levels of activity in genes associated with the production of various immune-related cells and chemical signalling factors, as well as those to do with inflammation (a general immune response that involves tissue swelling and increased immune-cell activity in the affected area). Although the researchers did not explicitly examine the health of their simian charges, chronic, generalised inflammation is a risk factor, in people, for a long list of ailments ranging from heart trouble to Alzheimer’s disease. Finally, the team investigated the mechanisms behind these differences in gene expression. In keeping with previous work, they found that high- and low-rank individuals showed different levels of responsiveness to a class of hormones called glucocorticoids, which regulate immune-system activity and response to stress. They also found changes in the mix of cells within the animals’ immune system itself. But what is new, and intriguing, is that they discovered, for the first time, evidence that a phenomenon called epigenetic change is at work. Epigenetics—currently one of molecular biology’s hottest topics—is a process by which genes are activated or deactivated by the presence or absence of chemical structures called methyl and acetyl groups. Dr Tung and Dr Gilad found that methylation patterns were systematically different in high- and low-ranking animals. Crucially, these changes are generally passed on to the daughter cells produced when a cell divides, and are thus perpetuated throughout an animal’s life. To the extent that epigenetic marking is involved in creating social status, then, status may be being maintained by the animal’s cells as they replicate. Destiny’s child? Those who believe in progress will, however, be pleased to know that epigenetics is not necessarily destiny. Methyl groups may help maintain the status quo, but if that status quo is interrupted by outside events they can be wiped away and a new lot put in place. Dr Tung and Dr Gilad discovered this because a few of their monkeys did change status within their groups. When that happened, changes in gene expression appropriate to the new status quickly followed. Those who do break free from their lowly station, then, may begin to reap the health benefits almost immediately. As with any animal study, this one cannot simply be mapped straight onto humans. But it does provide pointers that researchers who work on people can use. In particular, the experiment ensured that social rank was the only factor being changed, providing strong evidence that the chain of causality runs from low social status, through a disrupted immune system to worse health, and not the other way around. The best medicine, then, is promotion. Prosper, and live long

Depressive Cognition Scale

Negative thinking is a red flag for clinical depression. Stopping such thoughts early on can save millions of people from mental illness, according research study from the Frances Payne Bolton School of Nursing at Case Western Reserve University. Jaclene Zauszniewski, the Kate Hanna Harvey Professor in Community Health Nursing and associate dean for doctoral education at the school, has developed a brief 8-item survey to help healthcare providers identify depressive thinking patterns that may lead to serious depression if not identified and addressed early. Zauszniewski’s Depression Cognition Scale (DCS) asks individuals to respond to questions about helplessness, hopelessness, purposelessness, worthlessness, powerlessness, loneliness, emptiness and meaninglessness using a scale that ranges from “strongly agree” to “strongly disagree.” “Clinicians need guidelines and measures to know when negative thinking has reached a tipping point and has begun to spiral into clinical depression,” she said. The DCS has been used effectively to screen for more serious depressive symptoms in persons in the U.S. and around the world, but the researchers wanted to take it further and determine the point at which negative thinking establishes a pattern for the onset of clinical depression—even without other emotional expressions or body symptoms associated with depression. In a study of 629 healthy adults from 42 states who responded to questions through the Internet survey, they found the answer. Participants ranged in age from 21 to 84 years, and 70 percent were women; women make up the majority depression sufferers. The majority of the participants were college educated and had incomes greater than $40,000. For this study, the researchers compared DCS scores to the Center for Epidemiologic Studies Depression Scale (CES-D), which is recognized as a “gold standard” measure for identifying clinically significant depressive symptoms. Their goal was to determine a cut score on the DCS that would represent the point at which individuals may benefit from learning ways to change negative thinking in order to prevent serious depression. They found that a score of 7 on the DCS would be that point at which individuals should begin initiating strategies to change negative thoughts into positive ones. The findings also showed that at this cut score, the DCS accurately differentiated between persons with and without clinical depressive symptoms as determined by the CES-D. Zauszniewski and Abir K. Bekhet, a researcher from Marquette University in Milwaukee, report their findings in Issue 34 of the Western Journal of Nursing Research article, “Screening Measure for Early Detection of Depressive Symptoms: The Depressive Cognition Scale.”

Social ranking and Stress

Social stress changes immune system gene expression in primatesopen original article Tue Apr 10, 2012 18:11 from RSS 2.0 by University of Chicago Medical Center The ranking of a monkey within her social environment and the stress accompanying that status dramatically alters the expression of nearly 1,000 genes, a new scientific study reports. The research is the first to demonstrate a link between social status and genetic regulation in primates on a genome-wide scale, revealing a strong, plastic link between social environment and biology. In a comparison of high-ranking rhesus macaque females with their low-ranking companions, researchers discovered significant differences in the expression of genes involved in the immune response and other functions. When a female’s rank improved, her gene expression also changed within a few weeks, suggesting that social forces can rapidly influence genetic regulation. “We were able to use gene expression to classify individuals based on their rank,” said Yoav Gilad, PhD, associate professor of human genetics at the University of Chicago Biological Sciences and senior author of the study in PNAS. “Demonstrating these very plastic and temporal changes was novel and quite interesting.” The research, led by University of Chicago postdoctoral researcher Jenny Tung, was conducted with rhesus macaques housed in groups of five at the Yerkes National Primate Research Center in Atlanta. As in the wild, each group self-organizes into a dominance hierarchy, defined by which individual yields first during competition over food, water and grooming partners. In captivity, dominance is determined by the order of introduction into the group, giving researchers an opportunity to study how changes in rank lead to biological effect. “In the wild, females would not ordinarily leave the social group they were born into,” said Tung, PhD, now an assistant professor of evolutionary anthropology at Duke University. “They inherit their social rank from their mothers. But in this unnatural situation, order of introduction determines rank – the newcomer is generally lower status.” Previous research on rhesus macaques discovered that social rank influenced components of the stress response, brain, and immune system. With gene chip technology for measuring the expression of over 6,000 different genes, Tung, Gilad and colleagues at Yerkes, Emory University, and Johns Hopkins looked for the first time in primates at the effects of social rank on genetic function. Comparing 49 different female monkeys of different rank revealed significant changes in the expression of 987 genes, including 112 genes associated with immune system function. The result fits with data in monkeys where low rank and chronic stress lead to compromised immune function, and, more loosely, with human studies linking low socioeconomic status and high social stress to elevated disease risk. The overall genetic “signature” of expression changes was robust enough that researchers could predict an individual monkey’s social rank with high accuracy from their gene expression profile alone. That predictive power also enabled an unanticipated second test of whether gene expression would reflect unplanned changes in dominance rank. “It was a fortunate event in the experiment,” Gilad said. “When a couple of animals were removed from cages for various reasons and new ones were introduced to the groups, it turned out to improve the rank of a few monkeys. We could take advantage of this switch and see if our classifier still works.” By analyzing blood samples from these monkeys before and after their move, the researchers were able to use gene expression signatures to correctly predict the change in rank for six of seven monkeys. The result demonstrates that socially-induced gene expression changes are not stable, but can change rapidly in response to changes in social environment. “There’s a spooky side to this kind of research, in that an individual’s social rank is partially determining health status,” Tung said. “But there’s also a hopeful side. For the seven females that changed ranks, their gene status changed with them. They’re not stuck in place, and I think that says something more broadly about the capacity for change.” The researchers also investigated the mechanisms by which social status could influence gene expression. Dominance rank affected signaling of the glucocorticoid “stress hormone” system and the cell composition of blood samples, both of which contributed to changes in gene expression. Experiments also demonstrated for the first time that social rank influenced the DNA methylation status of many genes, an epigenetic mechanism of transiently turning genes on and off. Genes that changed expression with rank status were more likely to be methylated than unaffected genes, suggesting that this mechanism also plays a role in the social influence on genetic regulation. “That’s a novel mechanism that people haven’t considered in primates,” Gilad said. “I know that some have been resistant to the possibility of methylation changes on this timescale, but this is a demonstration that this mechanism also matters.” The authors caution that the experiments used monkeys in captivity, and stressed that the relationship between stress and gene regulation in the wild might not look the same. The influence of social factors on human genetics also remains to be tested, and measuring status while controlling for confounding factors in people would be a difficult endeavor, Gilad said. But if social stress does in fact influence human health, the current research provides some optimism. “An encouraging message to humans is the fact that the effects are plastic, reversible and change on a really large scale when rank changes,” Gilad said. “Whatever it is that causes stress through social environment, you might be able to fix.”

Depression patterns

Depressed individuals with a tendency to ruminate on negative thoughts, i.e. to repeatedly think about particular negative thoughts or memories, show different patterns of brain network activation compared to healthy individuals, report scientists of a new study in Biological Psychiatry. The risk for depression is increased in individuals with a tendency towards negative ruminations, but patterns of autobiographic memory also may be predictive of depression. When asked to recall specific events, some individuals have a tendency to recall broader categories of events instead of specific events. This is termed overgeneral memory and, like those who tend to ruminate, these individuals also have a higher risk of developing depression. These self-referential activities engage a network of brain regions called the default mode network, or DMN. Prior studies using imaging techniques have already shown that the DMN activates abnormally in individuals with depression, but the relationship between DMN activity and depressive ruminations was not clear. In this new report, Dr. Shuqiao Yao of Central South University in Hunan, China and colleagues evaluated DMN functional connectivity in untreated young adults experiencing their first episode of major depression and healthy volunteers. Each participant underwent a brain scan and completed tests to measure their levels of rumination and overgeneral memory. As expected, the depressed patients exhibited higher levels of rumination and overgeneral memory than did the control subjects. They also observed increased functional connectivity in the anterior medial cortex regions and decreased functional connectivity in the posterior medial cortex regions in depressed patients compared with control subjects. Among the depressed subjects, an interesting pattern of dissociation emerged. The increased connectivity in anterior regions was positively associated with rumination, while the decreased connectivity in posterior regions was negatively associated with overgeneral memory. Dr. Yao commented on the importance of these findings: “In the future, resting-state network activity in the brain will provide useful models for investigating network features of cognitive dysfunction in psychopathology.” “As we dig deeper in brain imaging studies, we are becoming increasingly interested in the activity of brain circuits rather than single brain regions,” said Dr. John Krystal, Editor of Biological Psychiatry. “Although it is a more complicated process, studying brain circuits may provide greater insight into symptoms, such as depressive ruminations. The current study nicely illustrates how altered activity at different sites within a brain network may be related to different features of depression.”