Category: Anxiety

Studies in twin pairs suggest that 40% of the risk for panic disorder is heritable, yet the manner in which genes contribute to the risk for panic disorder is far from clear. To date, variations in a growing number of genes have been implicated in the risk for panic disorder, but the magnitude of the impact of each individual gene is relatively small.

The pattern of these implicated genes raises the question of whether there might be molecular "switches" that control the function of groups of genes in a coordinated fashion, which would help to explain the observed findings related to the genetics of panic disorder.

A new study published in the current issue of Biological Psychiatry now implicates one type of molecular switch, microRNAs (miRNAs), in panic disorder.

Ribonucleic acid (RNA) is the immediate product of DNA. The most commonly discussed products of RNA are proteins, hence the common dictum "DNA makes RNA and RNA makes protein." However, miRNAs are small bits of RNA that bind to DNA and control the expression of various genes. There are a large number of miRNAs that have diverse effects on gene expression.

Through case-control studies in three different populations, from Spain, Finland and Estonia, Muiños-Gimeno, Espinosa-Parrilla and colleagues found that at least four miRNAs (miR-22, miR-138-2, miR-148a and miR-488) may be involved in the pathophysiology of panic disorder. Their subsequent functional studies revealed that miR-138-2, miR-148a and miR-488 repress several candidate genes for panic disorder including GABRA6, CCKBR and POMC, respectively, and that miR-22 regulates four other candidate genes: BDNF, HTR2C, MAOA and RGS2. Their analysis also implicated miR-22 and miR-488 in the regulation of anxiety related pathways in the brain.

"These data provide important new evidence that variation in genes coding for miRNAs may coordinate the involvement of a number of risk genes and thereby contribute to the development of panic disorder," commented Dr. John Krystal, Editor of Biological Psychiatry.

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Journal Reference:

1. Margarita Muiños-Gimeno, Yolanda Espinosa-Parrilla, Monica Guidi, Birgit Kagerbauer, Tessa Sipilä, Eduard Maron, Kristi Pettai, Laura Kananen, Ricard Navinés, Rocío Martín-Santos. Human microRNAs miR-22, miR-138-2, miR-148a, and miR-488 Are Associated with Panic Disorder and Regulate Several Anxiety Candidate Genes and Related Pathways. Biological Psychiatry, 2011; 69 (6): 526 DOI: 10.1016/j.biopsych.2010.10.010

Stimulation of a distinct brain circuit that lies within a brain structure typically associated with fearfulness produces the opposite effect: Its activity, instead of triggering or increasing anxiety, counters it.

That's the finding in a paper by Stanford University School of Medicine researchers to be published online March 9 in Nature. In the study, Karl Deisseroth, MD, PhD, and his colleagues employed a mouse model to show that stimulating activity exclusively in this circuit enhances animals' willingness to take risks, while inhibiting its activity renders them more risk-averse. This discovery could lead to new treatments for anxiety disorders, said Deisseroth, an associate professor of bioengineering and of psychiatry and behavioral science.

The investigators were able to pinpoint this particular circuit only by working with a state-of-the-art technology called optogenetics, pioneered by Deisseroth at Stanford, which allows brain scientists to tease apart the complex circuits that compose the brain so these can be studied one by one.

"Anxiety is a poorly understood but common psychiatric disease," said Deisseroth, who is also a practicing psychiatrist. More than one in four people, in the course of their lives, experience bouts of anxiety symptoms sufficiently enduring and intense to be classified as a full-blown psychiatric disorder. In addition, anxiety is a significant contributing factor in other major psychiatric disorders from depression to alcohol dependence, Deisseroth said.

Most current anti-anxiety medications work by suppressing activity in the brain circuitry that generates anxiety or increases anxiety levels. Many of these drugs are not very effective, and those that are have significant side effects such as addiction or respiratory suppression, Deisseroth said. "The discovery of a novel circuit whose action is to reduce anxiety, rather than increase it, could point to an entire strategy of anti-anxiety treatment," he added.

Ironically, the anti-anxiety circuit is nestled within a brain structure, the amygdala, long known to be associated with fear. Generally, stimulating nervous activity in the amygdala is best known to heighten anxiety. So the anti-anxiety circuit probably would have been difficult if not impossible to locate had it not been for optogenetics, a new technology in which nerve cells in living animals are rendered photosensitive so that action in these cells can be turned on or off by different wavelengths of light. The technique allows researchers to selectively photosensitize particular sets of nerve cells. Moreover, by delivering pulses of light via optical fibers to specific brain areas, scientists can target not only particular nerve-cell types but also particular cell-to-cell connections or nervous pathways leading from one brain region to another. The fiber-optic hookup is both flexible and pain-free, so experimental animals' actual behavior as well as their brain activity can be monitored.

In contrast, older research approaches involve probing brain areas with electrodes to stimulate nerve cell firing. But an electrode stimulates not only all the nerve cells that happen to be in the neighborhood but even fibers that are just passing through on the way to somewhere else. Thus, any effect from stimulating the newly discovered anti-anxiety circuit would have been swamped by the anxiety-increasing effects of the dominant surrounding circuitry.

In December 2010, the journal Nature Methods bestowed its "Method of the Year" title on optogenetics.

In the new Nature study, the researchers photosensitized a set of fibers projecting from cells in one nervous "switchboard" to another one within the amygdala. By carefully positioning their light-delivery system, they were able to selectively target this projection, so that it alone was activated when light was pulsed into the mice's brains. Doing so led instantaneously to dramatic changes in the animals' behavior.

"The mice suddenly became much more comfortable in situations they would ordinarily perceive as dangerous and, therefore, be quite anxious in," said Deisseroth. For example, rodents ordinarily try to avoid wide-open spaces such as fields, because such places leave them exposed to predators. But in a standard setup simulating both open and covered areas, the mice's willingness to explore the open areas increased profoundly as soon as light was pulsed into the novel brain circuit. Pulsing that same circuit with a different, inhibitory frequency of light produced the opposite result: the mice instantly became more anxious. "They just hunkered down" in the relatively secluded areas of the test scenario, Deisseroth said.

Standard laboratory gauges of electrical activity in specific areas of the mice's amygdalas confirmed that the novel circuit's activation tracked the animals' increased risk-taking propensity.

Deisseroth said he believes his team's findings in mice will apply to humans as well. "We know that the amygdala is structured similarly in mice and humans," he said. And just over a year ago a Stanford team led by Deisseroth's associate, Amit Etkin, MD, PhD, assistant professor of psychiatry and behavioral science, used functional imaging techniques to show that human beings suffering from generalized anxiety disorder had altered connectivity in the same brain regions within the amygdala that Deisseroth's group has implicated optogenetically in mice.

The study was funded by the National Institutes of Health, the National Institute of Mental Health, the National Institute on Drug Abuse, the National Science Foundation, NARSAD, a Samsung Scholarship, and the McKnight, Woo, Snyder, and Yu foundations. Kay Tye, PhD, a postdoctoral researcher in the Deisseroth laboratory, and Rohit Prakash, Sung-Yon Kim and Lief Fenno, all graduate students in that lab, shared first authorship. Other co-authors are graduate student Logan Grosenick, undergraduate student Hosniya Zarabi, postdoctoral researcher Kimberly Thompson, PhD, and research associates Viviana Gradinaru and Charu Ramakrishnan, all of the Deisseroth lab.

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Journal Reference:

1. Kay M. Tye, Rohit Prakash, Sung-Yon Kim, Lief E. Fenno, Logan Grosenick, Hosniya Zarabi, Kimberly R. Thompson, Viviana Gradinaru, Charu Ramakrishnan, Karl Deisseroth. Amygdala circuitry mediating reversible and bidirectional control of anxiety. Nature, 2011; DOI: 10.1038/nature09820

Researchers have for decades hypothesized that negative emotions lead to inflated reports of common physical symptoms, like headaches or an upset stomach. But a new University of Iowa study suggests that two negative emotions — depression and anxiety — influence symptom reporting in different ways.

Published in the latest issue of the Journal of Personality and Social Psychology, the study indicates that people who feel depressed report experiencing a higher number of past symptoms. People who feel anxious, by contrast, report more symptoms in the present moment.

Understanding how factors such as mood influence symptom reporting is important because physicians make diagnosis and treatment decisions based on the symptoms patients report, how intense they are, and how frequently they occurred, said study author Jerry Suls, a professor of psychology in the UI College of Liberal Arts and Sciences and a visiting scientist at the National Cancer Institute in Washington, D.C.

Previous studies have linked inflated symptom reports to "negative affect," a disposition also known as neuroticism. One-fifth of the population is believed to have this general tendency, which involves frequent feelings of anger, anxiety, fear, irritation or sadness. However, when the UI researchers examined the influence of temperament on symptom recall, they isolated each emotion rather than lumping them together.

"Our data suggest that a person who walks into a physician's office feeling sad will tend to recall experiencing more symptoms than they probably really did," Suls said. "If a person comes into the physician's office feeling fearful, they're more likely to scan their body and read any sensations they're experiencing at that moment as something wrong. We believe this is because depression is associated with rumination and exaggerated recall of negative experiences, while anxiety is associated with vigilance for potentially negative things in the present time."

Suls co-authored the study with Bryant Howren, a post-doctoral scholar in the UI Department of Psychology and the Center for Research in the Implementation of Innovative Strategies in Practice (CRIISP) at the Veterans Affairs Medical Center in Iowa City.

In the first part of the study, 144 undergraduate students completed questionnaires to assess their level of "depressive affect," and indicated which of 15 common physical symptoms they'd experienced in the past three weeks. Even after factoring out physical signs of depression, like appetite changes or sleep loss, researchers found that people who felt more depressed believed they had experienced more symptoms.

"Is it possible they actually did experience more symptoms? Sure," Suls said. "But all of these folks were nominally healthy. It's likely that each one experienced roughly the same number in terms of actual symptoms, but those who happened to be feeling blue thought they had experienced more."

Another phase of the study examined current symptom reporting. A sample of 125 undergraduates were assigned to groups. To induce a specific mood, each group wrote in detail for 15 minutes about an experience that made them feel angry, anxious, depressed, happy or neutral. They then completed a checklist to indicate which of 24 symptoms (weakness/fatigue, cardiorespiratory, musculoskeletal, and gastrointestinal) they currently felt. Participants in the anxious mood category reported higher numbers of physical symptoms.

"People could say, 'Well, you made them anxious — isn't that going to produce a physiologic reaction, like a pounding heart or sweaty palms?'" Suls said. "But we observed a general increase in all current physical symptoms — fatigue, for example, which isn't typically a consequence of feeling fearful or nervous."

Researchers repeated the writing exercise with another group of 120 students — only this time they asked participants to report both current and retrospective symptoms. On average, people in the anxious group reported five current symptoms, while those in the depressed and neutral groups only reported one or two. Reflecting on the past three weeks, the sad participants reported experiencing seven symptoms on average, while the other groups only recalled about three.

"Making people feel sad didn't influence what they reported feeling at the moment, but it was associated with reporting having had more symptoms in the recent past," Suls said. "With anxiety, we saw exactly the opposite. They didn't report more symptoms over the past three weeks, but at the moment they reported more."

Suls and Howren aren't encouraging health care providers to discount symptoms by virtue of the patient's mood. They do, however, encourage medical professionals to be aware that different emotions appear to play into how patients perceive their current and past symptoms.

"Ideally, a doctor would engage with the patient briefly to get a sense whether they're experiencing anxiety or sadness at the time of the visit," Suls said. "In some cases, it may be worthwhile to ask a significant other what they've observed in terms of symptoms, or to ask the patient to keep a symptom diary to ensure accuracy."

The age of participants was a limitation of the study, though the authors intentionally chose healthy college students to reduce confounds. Other studies indicate that emotional instability (such as depressed or anxious moods) decreases around age 40, so older adults may be less subject to recall or encoding biases associated with physical symptoms. Suls and Howren will focus future symptom-reporting research on older or chronically ill adults.

The research was supported in part by a National Institute on Aging grant awarded to Suls and a post-doctoral fellowship from the VA awarded to Howren.

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Journal Reference:

1. M. Bryant Howren, Jerry Suls. The symptom perception hypothesis revised: Depression and anxiety play different roles in concurrent and retrospective physical symptom reporting.. Journal of Personality and Social Psychology, 2011; 100 (1): 182 DOI: 10.1037/a0021715

The depression and anxiety experienced by many women after a miscarriage can continue for years, even after the birth of a healthy child, according to a study led by University of Rochester Medical Center researchers and published online by the British Journal of Psychiatry.

"Our study clearly shows that the birth of a healthy baby does not resolve the mental health problems that many women experience after a miscarriage or stillbirth," said Emma Robertson Blackmore, Ph.D., assistant professor of Psychiatry at the Medical Center and the lead researcher. "This finding is important because, when assessing if a women is at risk of antenatal or postnatal depression, previous pregnancy loss is usually not taken into account in the same way as other risk factors such as a family history of depression, stressful life events or a lack of social support."

"We know that maternal depression can have adverse impacts on children and families," Robertson Blackmore said. "If we offer targeted support during pregnancy to women who have previously lost a baby, we may be able to improve health outcomes for both the women and their children."

Pregnancy loss by miscarriage or stillbirth affects more than an estimated one million women in the United States annually. Between 50 and 80 percent of women who experience pregnancy loss become pregnant again.

The researchers studied 13,133 pregnant women in the United Kingdom who were taking part in a long-term study known as the Avon Longitudinal Study of Parents and Children. The women were asked to report the number of previous miscarriages and stillbirths they had experienced. They were assessed for symptoms of depression and anxiety twice during their pregnancy and four times after giving birth, at 8 weeks, 8 months, 21 months and 33 months. The majority of women reported no miscarriages. But 2,823 women, or 21 percent, reported having one or more previous miscarriages, while 108 reported having one previous stillbirth and three women had two previous stillbirths.

"We found no evidence that affective symptoms associated with previous prenatal loss resolve with the birth of a healthy child. Rather, previous prenatal loss showed a persisting prediction of depressive and anxiety symptoms well after what would conventionally be defined as the postnatal period," the researchers concluded.

Of the women who had one miscarriage or stillbirth before giving birth to a healthy child, for example, almost 13 percent still had symptoms of depression 33 months after the birth. Of those with two previous losses, almost 19 percent had symptoms of depression 33 months after the birth of a healthy child.

Prenatal loss is not routinely considered a risk factor for antenatal or postpartum depression in the same way as, for instance, personal or family history of depression, exposure to stressful life events or lack of social support, according to the study. Routinely assessing loss history would be valuable as a predictor of current and postpartum risk and as a possible marker for intervention, the researcher.

"Given the adverse outcomes of persistent maternal depression on both child and family outcomes, early recognition of symptoms can lead to preventive interventions to reduce the burden of illness, provide coping strategies to reduce anxiety and depression and promote healthy adjustment of the mother, family and child," the researchers stated.

In addition to Robertson Blackmore, the authors of the study include: Denise Côté-Arsenault, Ph.D., associate professor at the University of Rochester School of Nursing; Wan Tang, Ph.D., research assistant professor of Biostatistics, and Thomas G. O'Connor, Ph.D., professor of Psychiatry, both of the Medical Center; Vivette Glover, Ph.D., professor of Perinatal Psychobiology at the Imperial College School of Medicine, London, United Kingdom; and Jonathan Evans, Ph.D., consultant senior lecturer in Psychiatry, and Jean Golding, Ph.D., emeritus professor of Pediatrics and Perinatal Epidemiology, both of University of Bristol, United Kingdom.

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Journal Reference:

1. Emma Robertson Blackmore, Denise Côté-Arsenault, Wan Tang, Vivette Glover, Jonathan Evans, Jean Golding, and Thomas G. O’Connor. Previous prenatal loss as a predictor of perinatal depression and anxiety. The British Journal of Psychiatry, 2011; DOI: 10.1192/bjp.bp.110.083105

 A review of more than 160 studies of human and animal subjects has found "clear and compelling evidence" that — all else being equal — happy people tend to live longer and experience better health than their unhappy peers.

The study, in the journal Applied Psychology: Health and Well-Being, is the most comprehensive review so far of the evidence linking happiness to health outcomes. Its lead author, University of Illinois professor emeritus of psychology Ed Diener, who also is a senior scientist for the Gallup Organization, of Princeton, N.J., analyzed long-term studies of human subjects, experimental human and animal trials, and studies that evaluate the health status of people stressed by natural events.

"We reviewed eight different types of studies," Diener said. "And the general conclusion from each type of study is that your subjective well-being — that is, feeling positive about your life, not stressed out, not depressed — contributes to both longevity and better health among healthy populations."

A study that followed nearly 5,000 university students for more than 40 years, for example, found that those who were most pessimistic as students tended to die younger than their peers. An even longer-term study that followed 180 Catholic nuns from early adulthood to old age found that those who wrote positive autobiographies in their early 20s tended to outlive those who wrote more negative accounts of their young lives.

There were a few exceptions, but most of the long-term studies the researchers reviewed found that anxiety, depression, a lack of enjoyment of daily activities and pessimism all are associated with higher rates of disease and a shorter lifespan.

Animal studies also demonstrate a strong link between stress and poor health. Experiments in which animals receive the same care but differ in their stress levels (as a result of an abundance of nest mates in their cages, for example) have found that stressed animals are more susceptible to heart disease, have weaker immune systems and tend to die younger than those living in less crowded conditions.

Laboratory experiments on humans have found that positive moods reduce stress-related hormones, increase immune function and promote the speedy recovery of the heart after exertion. In other studies, marital conflicts and high hostility in married couples were associated with slow wound healing and a poorer immune response.

"I was almost shocked and certainly surprised to see the consistency of the data," Diener said. "All of these different kinds of studies point to the same conclusion: that health and then longevity in turn are influenced by our mood states."

While happiness might not by itself prevent or cure disease, the evidence that positive emotions and enjoyment of life contribute to better health and a longer lifespan is stronger than the data linking obesity to reduced longevity, Diener said.

"Happiness is no magic bullet," he said. "But the evidence is clear and compelling that it changes your odds of getting disease or dying young."

"Although there are a handful of studies that find opposite effects," Diener said, "the overwhelming majority of studies support the conclusion that happiness is associated with health and longevity. Current health recommendations focus on four things: avoid obesity, eat right, don't smoke, and exercise. It may be time to add 'be happy and avoid chronic anger and depression' to the list."

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Journal Reference:

1. Ed Diener, Micaela Y. Chan. Happy People Live Longer: Subjective Well-Being Contributes to Health and Longevity. Applied Psychology: Health and Well-Being, 2011; DOI: 10.1111/j.1758-0854.2010.01045.x

Emory University experts predict that rates of depressive disorders among men will increase as the 21st century progresses.

In an editorial published in the March 2011 issue of the British Journal of Psychiatry, author Boadie Dunlop, MD, writes "Compared to women, many men attach a great importance to their roles as providers and protectors of their families. Failure to fulfill the role of breadwinner is associated with greater depression and marital conflict."

Research shows that since the beginning of the recession in 2007, roughly 75 percent of the jobs lost in the United States were held by men. On the other hand, women are increasingly becoming the primary household earners with 22 percent of wives earning more than their husbands in 2007, versus only four percent in 1970. Unfortunately, there is little reason for anyone to believe that traditional male jobs will return in significant numbers with economic recovery.

Additionally, biological and sociological differences in men and women may make it harder for men to fit into the role of primary care provider to young children than most women.

"Men in the changing economy will face the same risks for depression that women faced in older economies: trapped in a family role from which they cannot escape because of an inability to find employment," Dunlop says.

Finally, the societal expectancy of men to be tough, stoic and hide their feelings is being significantly eroded. The growing awareness about mental health through education, and hearing prominent male figures talk about their depression, has had a significant impact in opening up the public space for men to validate symptoms of depression.

One of the most well established findings in the epidemiology of psychiatric disorders is that women have nearly twice the lifetime risk of developing major depressive disorder than men.

"The changing socioeconomic positions of the West could lead to prevalence in the rates of depression in men increasing, while rates in women decrease," warns Dunlop. "Practitioners need to be aware of these forces of life, and be prepared to explore with their patients the meaning of these changes and interventions that might be helpful."

Tanja Mletzko, research coordinator in the Mood an Anxiety Disorders Program, is co-author of this editorial.

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Journal Reference:

1. Boadie W. Dunlop, Tanja Mletzko. Will current socioeconomic trends produce a depressing future for men?British Journal of Psychiatry, 2011; 198: 167-168 DOI: 10.1192/bjp.bp.110.084210

Heart attack patients with a history of depression presenting at emergency departments were less likely to receive priority care than people with other conditions, found a study published in CMAJ (Canadian Medical Association Journal).

Several studies indicate that people with heart attacks and depression have worse outcomes than people without, although emergency department care has not been looked at as a possible contributor. In the United States, more than six million patients with mental health issues are seen in emergency departments each year and six million people visit for chest pain.

This study, by researchers from the Institute of Clinical Evaluative Sciences, looked at data on 6,874 patients admitted to 96 acute care hospitals in Ontario, Canada from April 2004 to March 2005. They found that 680 of these heart attack patients had a history of depression recorded in their medical charts, and 39% of these were assigned a low priority triage score in the emergency department, compared with 32.7% of the other patients with heart attacks.

"Ten per cent of acute myocardial infarction patients seen in the emergency department had a history of depression recorded in their chart, and it was associated with an increased risk of receiving a low priority emergency department triage score, as well as delays in diagnostic testing and definitive care," writes Dr. Clare Atzema, Institute for Clinical Evaluative Sciences, with coauthors. "Interestingly, other components of the medical history, including the traditional cardiac risk factors of diabetes, smoking, hypercholesterolemia and hypertension, were not associated with triage score in the models; only depression affected the score."

As well, a lower triage priority based on charted depression resulted in delays in diagnosis and treatment by physicians, nurses, cardiologists and laboratory teams.

The authors suggest this lower prioritizing by emergency staff may be based on assumptions that patients' symptoms are anxiety-related rather than due to an actual heart attack. Less than 10% of patients who come to emergency rooms with heart attack symptoms, such as chest pain or shortness of breath, are found to be suffering from the condition. Therefore staff are actively looking for other possible sources for the patients' symptoms.

"We suspect that mistriage of these patients is not due to purposeful discrimination by emergency department staff, but rather that most emergency department staff are unaware of data that suggests a link between depression and coronary artery disease," write the authors. They suggest this information needs to be disseminated to emergency room staff.

High blood levels of a hormone produced in response to stress are linked to post-traumatic stress disorder in women but not men, a study from researchers at Emory University and the University of Vermont has found.

The results are scheduled for publication in the Feb. 24 issue of Nature.

The hormone, called PACAP (pituitary adenylate cyclase-activating polypeptide), is known to act throughout the body and the brain, modulating central nervous system activity, metabolism, blood pressure, pain sensitivity and immune function. The identification of PACAP as an indicator of PTSD may lead to new diagnostic tools and eventually, to new treatments for anxiety disorders.

"Few biological markers have been available for PTSD or for psychiatric diseases in general," says first author Kerry Ressler, MD, PhD, associate professor of psychiatry and behavioral sciences at Emory University School of Medicine and a researcher at Yerkes National Primate Research Center. "These results give us a new window into the biology of PTSD."

Women, but not men, with high blood levels of PACAP display more of the symptoms of PTSD, such as difficulty discriminating between fear and safety signals and being easier to startle. In a group of 64 people, most of whom had experienced significant trauma, women with above-average PACAP levels had PTSD symptom scores five times those of women with less-than-average PACAP levels.

In addition, a variation in the gene for PACAP's receptor, which may change how that gene responds to estrogen, was also linked to PTSD risk in women only.

Ressler notes that despite comparable levels of trauma, women in the study with the more protective PACAP receptor gene variation have lower rates of PTSD than men, whereas those with the risk gene variation had higher rates of PTSD.

"What this says is that men and women who have been traumatized may arrive at PTSD by different biological pathways," Ressler says. "In this case, we have a clue how that works, in that the genetic data point to changes in the ability to respond to estrogen."

The findings emerged from the Grady Trauma Project, a study of more than 1200 low-income Atlanta residents with high levels of exposure to violence and physical and sexual abuse, resulting in high rates of civilian PTSD. Beginning in 2005, interviewers asked patients in primary care, ob-gyn, and other clinic waiting areas of Grady Memorial Hospital in Atlanta to complete questionnaires on their life histories and to provide saliva and blood samples for DNA and other analyses.

Ressler, a Howard Hughes Medical Institute Investigator, is co-director of the Grady Trauma Project, along with co-author Bekh Bradley, PhD, assistant professor of psychiatry and behavioral sciences at Emory and director of the Trauma Recovery Program at the Atlanta Veterans Affairs Medical Center.

To explore how the PACAP pathway responds to stress and hormones, Ressler and his team teamed up with colleagues at the University of Vermont who had been studying PACAP in animals. The Vermont researchers were led by Victor May, PhD, professor of anatomy and neurobiology. Co-authors Jom Hammack, PhD, and Donna Toufexis, PhD, both assistant professor of psychology at the University of Vermont, were previously postdoctoral fellows at Yerkes National Primate Research Center.

The Vermont team's previous experiments showed that in rats experiencing stress, PACAP is increased ten-fold in a part of the brain called the BNST (bed nucleus of the stria terminalis), which scientists have shown is critical for anxiety behavior. In the Nature paper, they demonstrate that the gene for the PACAP receptor is also activated by stress and the hormone estrogen.

"In the brain, PACAP can activate brain cells, and it is also neurotrophic, helping brain cells survive, grow and form connections," Hammack says. "In many brain areas, this is great, but in others, such as those involved in sustained anxiety behavior, this might not be so good."

"These studies may offer opportunities to distinguish people with PTSD and related anxiety disorders from other behavioral disorders, and identify people in high stress occupations or environments who may be prone to PTSD," says May.

Ressler says that it will be important to replicate the finding in separate population groups including in veterans with PTSD. In addition, identifying when PACAP levels rise in the brain and blood during the development of PTSD will help determine whether drugs that act against PACAP could aid in treatment.

The research was supported by the National Institutes of Health, the American Foundation for Suicide Prevention and the Burroughs Wellcome Fund.

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Journal Reference:

1. Kerry J. Ressler, Kristina B. Mercer, Bekh Bradley, Tanja Jovanovic, Amy Mahan, Kimberly Kerley, Seth D. Norrholm, Varun Kilaru, Alicia K. Smith, Amanda J. Myers, Manuel Ramirez, Anzhelika Engel, Sayamwong E. Hammack, Donna Toufexis, Karen M. Braas, Elisabeth B. Binder, Victor May. Post-traumatic stress disorder is associated with PACAP and the PAC1 receptor. Nature, 2011; 470 (7335): 492 DOI: 10.1038/nature09856

 The perception of negative stereotyping, particularly in the areas of financial services and automobile sales and service, can cause consumers to fear being duped and forgo their purchases, according to new research by University of Minnesota associate professor Kathleen D. Vohs.

Vohs, the Land O'Lakes Professor for Excellence in Marketing at the university's Carlson School of Management, and co-authors Hakkyun Kim (Concordia University, Canada) and Kyoungmi Lee (Yonsei University, Korea) found that a potential buyer, aware of negative associations held about a group to which he or she belongs, may experience apprehension when transacting with someone from outside this group. This nervousness detrimentally impacts purchasing decisions.

"People naturally withdraw from situations where they anticipate being stereotyped," says Vohs. "They fear being duped or inadvertently reinforcing the negative association."

In "Stereotype Threat in the Marketplace: Consumer Anxiety and Purchase Intentions," which will appear in a forthcoming issue of the Journal of Consumer Research, the researchers conducted three experiments.

The first focused on women's feelings when interacting with potential financial advisors. When predisposed to conditions meant to remind participants of the stereotype that women are less competent at math than men, women reported feeling more anxious about interacting with a male financial advisor and less inclined to procure financial services.

The second experiment tested these findings in an automobile repair context. When asked to report their gender before seeking a car repair, women were more likely to feel anxiety when contemplating a transaction with a male technician.

"Consumers don't have to believe the stereotype; they just have to be aware that the stereotype exists to experience the threat" Vohs adds. "The actual behavior of the salesperson may have little effect."

This research provides some of the first evidence that the presence of negative stereotypes plays an important role in consumer judgments. These findings have practical implications for marketers, who may take care to avoid using advertising content that might trigger thoughts or associations of a negative stereotype in potential costumers.

While marketers cannot completely control for which perceived stereotypes may cause anxiety in potential buyers in all cases at all times, Vohs and colleagues found they may be able to mitigate the stereotype threat by introducing a sense of calmness into the transaction environment.

In the study's third experiment, the researchers found that introducing the scent of vanilla into the decision-making process helped participants feel calmer and more assured of their transaction.

"Vanilla scent has been used for centuries to calm and pacify people who have anxiety," says Vohs. "While we used scent, any tactics firms can employ that would calm consumers could help the transaction take place as the marketer would intend."

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Journal Reference:

1. Lee, Kyoungmi, Hakkyun Kim, and Kathleen D. Vohs. Stereotype Threat in the Marketplace: Consumer Anxiety and Purchase Intentions. Journal of Consumer Research, (in press) DOI: 10.1086/659315

Your blood and the level of a hormone in your spit could reveal if you're on the point of burnout, according to research undertaken by Dr. Sonia Lupien and Robert-Paul Juster of the Centre for Studies on Human Stress of Louis-H. Lafontaine Hospital and the University of Montreal.

In addition to professional and personal suffering, burnout puts distressed workers at further risk of physical and psychological problems if ignored. This is significant, as burnout, clinical depression, or anxiety related to the workplace affects at least 10% of North Americans and Europeans, according to estimates prepared by the International Labor Organization.

"We hypothesized that healthy workers with chronic stress and with mild burnout symptoms would have worse physiological dysregulations and lower cortisol levels — a profile consistent with burnout," Juster explained. Cortisol is a stress hormone involved in our bodies stress response and naturally as part of our body's daily rhythm. Cortisol levels are often high in people suffering from depression, while it tends to be low in cases of burnout. Too much cortisol can be as bad as too little when it comes to both mental and physical health.

Chronic stress and misbalanced cortisol levels can exert a kind of domino effect on connected biological systems. The term "allostatic load" represents the physiological problems or 'wear and tear' that ensue in these different systems related to risks for diabetes, cardiovascular disease, and immune problems. By looking at various factors such as insulin, sugar, cholesterol, blood pressure, and inflammation, an allostatic load index can be constructed and then used to detect problems before they occur. "The strength of the allostatic load model is its flexible inclusion of numerous biological systems that get strained by chronic stress. Complementary use of saliva samples and validated questionnaires allows us to go beyond measuring susceptibilities to, say, metabolic syndromes or heart problems, but also into the realm of mental health," Juster said.

The results of this first pilot study were obtained by testing thirty middle-aged participants. In addition to undergoing routine blood measures that assessed allostatic load, participants were instructed to collect saliva at home and during a laboratory paradigm. They also filled out questionnaires related to their current stress levels as well as symptoms of depression and burnout.

This research is part of a greater effort to develop personalized medicine in this field. Personalized medicine targets the customization of treatment according to the needs of the individual. "In an effort to advance person-centered approaches in prevention and treatment strategies, we have to investigate the biopsychosocial signatures of specific diseases," Lupien said. "For conditions like burnout where we have no consensus on diagnostic criteria and where there is overlap with symptoms of depression, it is essential to use multiple methods of analysis. One potential signature of burnout appears to be fatigued production of the stress hormone cortisol and dysregulations of the physiological systems that interact with this stress hormone."

Critically, people with burnout are often treated with anti-depressant medications that lower cortisol levels. If cortisol is already lower than it should be, this course of treatment could represent a therapeutic mistake. "The use of an allostatic load index gives researchers and clinicians a window to see how chronic stress is straining the person. In the future, we need studies that track people over time to determine whether this profile of low cortisol and physiological dysregulations is indeed burnout's autograph. If so, science will be one step closer to helping distressed workers before they burn out," Juster noted.

The research was published in Psychoneuroendocrinology and received funding from the Canadian Institutes of Health Research. Dr. Sonia Lupien is Scientific Director of Fernand-Seguin Research Centre of Louis-H. Lafontaine Hospital and is an associate professor with the Department of Psychiatry at Université de Montréal. Dr. Lupien is the Founder and Director of the Centre for Studies on Human Stress. She also holds a Senior Investigator Chair on Sex, Gender and Mental Health from the Canadian Institute of Gender and Health (IGH). Juster is affiliated with the Fernand-Seguin Research Centre of Louis-H. Lafontaine Hospital and the Centre for Studies on Human Stress. He's a Ph.D. candidate in the Department of Neurology and Neurosurgery at McGill University.

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Journal Reference:

1. Robert-Paul Juster, Shireen Sindi, Marie-France Marin, Andrea Perna, Alireza Hashemi, Jens C. Pruessner, Sonia J. Lupien. A clinical allostatic load index is associated with burnout symptoms and hypocortisolemic profiles in healthy workers. Psychoneuroendocrinology, 2010; DOI: 10.1016/j.psyneuen.2010.11.001