In a study published online in the Nov. 22 edition of Psychotherapy and Psychosomatics, researchers randomly assigned 30 sedentary women, ages 18-37 who were diagnosed with GAD, to either a control group or six weeks of strength or aerobic exercise training. Women in the exercise conditions completed two weekly sessions of either weight lifting or leg cycling exercise. Remission of the disorder, determined by psychologists who were unaware of the treatment each client received, was higher among exercisers and best among those who performed weight lifting exercise. Worry symptoms, the primary problem among individuals with GAD, were significantly reduced among the exercisers, and moderate-to-large improvements in other symptoms, such as irritability, feelings of tension, low energy and pain, were found.

Matthew Herring, now a research associate in the department of epidemiology at the University of Alabama, Birmingham, led the study during his dissertation research as a doctoral student in the UGA College of Education’s department of kinesiology. The team also included Patrick O’Connor and Rodney Dishman, co-directors of the UGA exercise psychology laboratory, psychology professor Cynthia Suveg and doctoral student Marni Jacob.

“Our findings add to the growing body of evidence of the positive effects of exercise training on anxiety,” said Herring. “Our study is the first randomized controlled trial focused on the effects of exercise training among individuals diagnosed with GAD. Given the prevalence of GAD and drawbacks of current treatments, including expense and potential negative side effects, our findings are particularly exciting, because they suggest that exercise training is a feasible, well-tolerated potential adjuvant therapy with low risk that can reduce the severity of signs and symptoms of GAD. Future research should confirm these findings with large trials and explore potential underlying mechanisms of exercise effects among individuals with GAD.”

The study also examined potential interactions between exercise and drugs used to treat GAD. Half of the participants in each group were taking a medication to treat GAD during the exercise program. Exercise training lessened anxiety symptoms to the same degree among those taking medication compared to those not taking medication.

“The large improvements found in this small investigation show that regular exercise has the power to help calm women suffering from GAD, even among those who appear to be resistant to treatment using medication,” said O’Connor.

“The results of this research are very exciting because exercise is available to everyone, is relatively inexpensive and has beneficial effects beyond the reduction of anxious and depressive symptoms,” said Suveg. “For individuals suffering from impairing symptoms, these preliminary findings suggest that exercise may offer another potential treatment option that has few, if any, negative side effects. Future research needs to explore the long-term benefits of exercise as well as the conditions under which exercise may be most beneficial and for whom.”

The study was supported by a grant from the UGA College of Education.

Much of the work was done at the Jan and Dan L. Duncan Neurological Research Institute at Texas Children’s Hospital.

MeCP2 is a “Goldilocks” in the protein world. When the protein is lacking or defective, girls develop the neurological disorder Rett syndrome early in life. Too much protein results in the more recently identified MeCP2 duplication syndrome, which usually affects boys, who may inherit the gene duplications either from their mothers or, in rare cases, develop it sporadically. In both cases, anxiety and social behavioral deficits are typical of those with the disease, along with other motor problems and cognitive defects.

“This is a nice example of a translational story,” said Dr. Rodney Samaco, assistant professor of molecular and human genetics at BCM and first author of the paper. “We first identified the mouse model for MeCP2 duplication syndrome and then found people with the disorder in the clinic. We went back to the lab and found out that MeCP2 was indeed the major contributor to this phenotype in patients. We have now identified two genes involved in two major symptoms of the syndrome. Eventually, we may take the information back to the clinic to develop a treatment for patients.”

“Loss or Gain of MeCP2 affects the expression of hundreds of genes, but discovering that two genes are the culprits in mediating anxiety and social behavioral problems is surprising,” said Dr. Huda Zoghbi, professor of molecular and human genetics, neurology, neuroscience, and pediatrics at BCM and director of the NRI. She is the corresponding author of the report and a Howard Hughes Medical Institute Investigator.

Patients with MeCP2 duplication disorder have a duplication in chromosomes that span both the MECP2 gene and another called IRAK1. But with this new study, it is now clear that excess MeCP2 accounts for the neuropsychiatric symptoms.

In mice, doubled MeCP2 levels caused both anxiety and autism-like behaviors and altered the expression of several hundred genes. Of these, two genes – Crh and Oprm1, are implicated in anxiety and social behavior, said Samaco.

“Then, when we reduced the levels of Crh, we saw reduced anxiety,” he said. “When we reduced levels of Oprm1, we improved the social behavior problems.”

This finding is important because it shows that tweaking the expression of genes that the protein affects, rather than trying to adjust the levels of the finicky MeCP2 protein itself, can modify symptoms of MeCP2 disorders.

In fact, Samaco also reduced levels of the protein that is a cellular receptor for Crh, both through molecular means and with the use of a drug, and found that anxiety levels also went down. That could provide another means of dealing with anxiety associated with the duplication syndrome.

The Duke team found that noise-cancelling headphones playing a classical melody may reduce the pain and anxiety of the often uncomfortable procedure.

The finding, published this month in the journal Urology, points to a simple and inexpensive way to help an estimated 700,000 U.S. men who undergo a prostate biopsy a year. The procedure is essentially the only way to diagnose prostate cancer, which strikes one in six men during their lifetimes.

“It’s a matter of shifting attention, so the music provides a distraction from the procedure,” said Matvey Tsivian, M.D., a Duke urologic oncology fellow and lead author.

For the study, which was conceived by medical students and had no outside funding, the Duke team enrolled 88 patients and randomly assigned them to three groups. The first had no headphones; the second wore the noise-cancelling headphones but heard no music; and the third wore the headphones and listened to Bach concertos.

Blood pressure was taken before and after a trans-rectal biopsy, which is an intrusive procedure involving an ultrasound probe and a spring-loaded needle that has a loud trigger. The noise alone causes many men to flinch even if they report no pain, and 20 percent of men experience high stress and anxiety about the procedure.

Among study participants in both groups with no musical intervention, diastolic blood pressure remained elevated after the procedure, compared to before. But the men who wore the headphones and listened to Bach had no such spike in blood pressure. Diastolic blood pressure often rises as a function of stress and anxiety.

Study participants who had the music also reported less pain, as measured by questionnaires. The researchers said they did not determine whether the choice of music might have had an impact.

“We couldn’t study all the permutations and variables, but it’s evident that this kind of approach works,” said Thomas Polascik, M.D., director of Urologic Oncology at the Duke Cancer Institute and senior author of the study. “This is something that could be broadly employed. It’s easy and inexpensive – a set of headphones and music. That’s it.”

As part of a study on how the brain processes fear in anxious and non-anxious individuals, Tahl Frenkel, a Ph.D. candidate in TAU’s School of Psychological Sciences and the Adler Center for Research in Child Developmental and Psychopathology, working with her supervisor Prof. Yair Bar-Haim, measured brain activity as study participants were shown images designed to induce fear and anxiety. Using an EEG to measure electrical activity caused by the neuronal activity that represents deep processing of these stimuli, the researchers discovered that the anxious group was actually less stimulated by the images than the non-anxious group.

The results of the study were recently published in Biological Psychology.

Surprisingly, anxious study participants weren’t shown to be as physiologically sensitive to subtle changes in their environment as less fearful individuals, Frenkel explains. She theorizes that anxious people could have a deficit in their threat evaluation capabilities — necessary for effective decision-making and fear regulation — leading to an under-reaction to subtle threatening stimuli. Non-anxious individuals seem to have a subconscious “early warning system,” allowing them to prepare for evolving threats. Essentially, anxious people are “surprised” by fearful stimuli that non-anxious individuals have already subconsciously noticed, analyzed, and evaluated.

To get a more accurate picture of both behavioral and neural reactions to fear-inducing stimuli, the researchers drew participants from a group of 240 undergraduate students at the university. Using the Speilberger’s State-Trait Anxiety Inventory trait scale, they identified the 10 percent “most anxious” individuals and 10 percent “least anxious” individuals to participate in the final study.

In the first part of their study, the researchers measured behavioral responses to fear-inducing stimuli. A set of pictures, featuring a person looking progressively more fearful on a scale of 1-100, was shown to the participants. When shown the sequence of pictures, anxious people were quicker to respond to the fear in the subject’s face. They identified a face as being “fearful” at a rating of only 32, while non-anxious people did not describe the same face as fearful until it reached a rating of 39.

But the EEG data tells a different story, Frenkel says. The researchers also measured the participants’ brain waves by EEG while they were being shown the photographs and discovered that non-anxious individuals completed an in-depth processing of fear-inducing stimuli that informed their behavioral response, whereas anxious individuals did not.

When confronted with a potential threat, Frenkel concluded, non-anxious people unconsciously notice subtle changes in the environment before they consciously recognize the threat. Lacking such preparation, anxious individuals often react more strongly, as the threat takes them more “by surprise.”

“The EEG results tell us that what looks like hypersensitivity on a behavioral level is in fact the anxious person’s attempt to compensate for a deficit in the sensitivity of their perception,” she explains.

Delays in care after abnormal cancer screenings contribute to disparities in cancer out- comes. Women with psychiatric disorders are less likely to receive cancer screening and may also have delays in diagnostic resolution after an abnormal screening test. Vulnerable populations of women, as defined by low income or with racial/ethnic minority status, are less likely to receive standard preventive health care, which contributes to worse breast and cervical cancer outcomes. Depression is prevalent in these populations, and may lead to worse healthcare outcomes.

The BUSM researchers conducted a retrospective chart review of electronic medical records to identify women who had a diagnosis of depression or anxiety in the year prior to the abnormal mammogram or Pap test. They used time-to-event analysis to analyze the outcome of time to resolution after abnormal cancer screening.

Of the women with abnormal mammogram and Pap tests, the researchers found 19 percent and 16 percent, respectively, suffered with depression. The median time to resolution was 27 days for women with abnormal mammograms and 85 days for women with abnormal Pap tests. However, there was no difference in time to diagnostic resolution between depressed and not-depressed women for those with abnormal mammograms or Pap tests.

The researchers believe that documented mood disorders are not an additional barrier to resolution after an abnormal cancer screening test in this vulnerable population of women who already had barriers to receiving healthcare. “Although we found delays in diagnostic resolution after abnormal cancer screening, women with a depression diagnosis did not have increased delays compared to those who were not depressed,” explained lead author Andrea Kronman, MD, MSc, assistant professor of medicine at BUSM.

“Pre-screening the electronic medical records of women for mood disorders may not be the most reliable approach to identify a group of patients at higher risk of delayed diagnostic resolution of abnormal cancer screening tests in a vulnerable population,” added Kronman.

For the highly math anxious, researchers found a strong link between math success and activity in a network of brain areas in the frontal and parietal lobes involved in controlling attention and regulating negative emotional reactions. This response kicked in at the very mention of having to solve a mathematics problem.

Teachers as well as students can use the information to improve performance in mathematics, said Sian Beilock, associate professor in psychology at the University of Chicago. Beilock and PhD student Ian Lyons report their findings in the article, “Mathematics Anxiety: Separating the Math from the Anxiety,” published Oct. 20 in the journal Cerebral Cortex.

“Classroom practices that help students focus their attention and engage in the math task at hand may help eliminate the poor performance brought on by math anxiety,” said Beilock, a leading expert on mathematics anxiety and author of the book Choke: What The Secrets Of The Brain Reveal About Getting It Right When You Have To.

Instead of feeling anxious about an impending math task, students who could focus their attention were able to complete difficult math problems more successfully. Perhaps counter-intuitively, their success wasn’t just about activating areas of the brain involved in math calculation. For math-anxious individuals to succeed, they need to focus on controlling their emotions, Beilock said.

Lyons and Beilock said their work implies that teaching students to control their emotions prior to doing math may be the best way to overcome the math difficulties that often go along with math anxiety. Without this initial step, simply providing additional math instruction or allowing students to become distracted by trying to squelch emotions once a math exam has begun is likely to prove ineffective in producing math success.

The study, which the National Science Foundation funded, began by administering a questionnaire to a group of UChicago students to determine if they had math anxiety. Students answered questions about how anxious they felt when registering for a math course, walking to a challenging math class, being handed a math textbook and so on. Lyons and Beilock then invited a group of students who were especially anxious about these math-related tasks to have their brains scanned using functional magnetic resonance imaging (fMRI) while they performed difficult math problems and a similarly difficult spelling task. A group of non-math-anxious students was selected as a control group.

In the fMRI scanner, students watched a computer screen for different cues in the form of simple, color-coded shapes. One shape indicated to students they were about to answer questions that tapped their spelling skills, and another shape indicated they were about to do a series of math problems. After a short delay, students then performed a few math or spelling problems. By analyzing brain responses during the cue and problems separately, Lyons and Beilock were able to look at what went on in highly math-anxious student’s heads, even before the actual math began.

For the highly math-anxious, the researchers found a strong connection between math performance and activity in a network of brain areas in the frontal and parietal lobes.

The more these frontal and parietal regions were activated in math-anxious students when anticipating an impending math task, the more their math performance looked like the non-math-anxious control group. Indeed, highly math-anxious students who showed little activation in these regions when preparing to do math got only 68 percent of math problems correct. But those who showed the strongest activation got 83 percent correct — nearly on par with low math-anxious controls (88 percent correct). This relationship was not seen for the spelling task.

The study found that for the highly math-anxious students who performed well on the math task, the brain activity that started during the anticipation phase initiated a cascade of brain activity during completion of the math task itself. This activity did not involve areas typically associated with performing numerical calculations. Rather, it was seen in subcortical structures — especially caudate and nucleus accumbens — associated with motivation and juggling risks and rewards with the demands of the task at hand.

“Essentially, overcoming math anxiety appears to be less about what you know and more about convincing yourself to just buckle down and get to it,” Beilock said. “But if you wait till the math exam has already started to deal with your anxiety, it’s already too late,” Lyons added.

For students who were not anxious about math to begin with, there was no relationship between activation in brain areas important for focusing attention, controlling emotion and math performance. This shows that approaching math may be entirely different for high and low math-anxious students. “Think about walking across a suspension bridge if you’re afraid of heights versus if you’re not — completely different ballgame,” Lyons said.

The study also sheds light on how people who get nervous about doing math can put their fears aside in everyday situations, such as balancing a checkbook or figuring out a tip among friends or coworkers. Taking a few breaths before jumping in can help one focus less on preparing to do math, and more on what actually needs to be done. “When you let your brain do its job, it usually will,” Lyons said. “If doing math makes you anxious, then your first task is to calm yourself down.”

The study suggests that, in addition to our genes, our life experiences are important influences on our levels of anxiety and depression.

“In this time of emphasis on genes for this and that trait, it is important to remember that our environmental experiences also make important contributions to who we are as people,” said principal investigator Kenneth Kendler, M.D., director of the VCU Virginia Institute for Psychiatric and Behavioral Genetics.

“When I was growing up, in talking about the importance of a good diet, we used to say ‘You are what you eat.’ What this study shows is that to a substantial degree, ‘you are what you have experienced.’ That is, your life history stays with you in impacting on your background book, for good or for ill,” he said.

Kendler, professor of psychiatry, and human and molecular genetics in the VCU School of Medicine, and an international team of researchers from VCU and other universities, analyzed nine data sets of more than 12,000 identical twins with symptoms of depression and/or anxiety through the lifespan.

By studying identical twins, researchers have a pair of individuals who are born with identical genetic compositions and a shared family environment. Their environments may begin to change as they begin to make divergent decisions as they get older that come with lifestyle, diet or friends.

Participants completed reports relating to their own symptoms of anxiety and depression in a five-to-six-year period. The participants varied in age and were from American and European population-based registries.

According to Kendler, statistical models, developed by his colleague Charles Gardner, Ph.D., a research associate in the VCU Department of Psychiatry, were used to observe how components of individual variation changed over time. The team observed that as the twins moved from childhood into late adult life, they increasingly diverged in their predicted levels of symptoms, but after that point, stopped further diverging. Further, they noted that environmental experiences contribute substantially to stable and predictable inter-individual differences in levels of anxiety and depression by mid-life in adults.

The study first appeared online Sept. 23, and in the October issue of Psychological Science, a journal of the Association for Psychological Science. Read the journal’s news release here.

Kendler collaborated with VCU researchers Lindon Eaves, Ph.D., Erik Loken, Ph.D., Judy Silberg, Ph.D., and Charles Gardner, Ph.D.; Nancy Pedersen, Ph.D., and Paul Lichtenstein, Ph.D.,  with the Karolinska Institutet in Stockholm, Sweden; Christel M. Middeldorp and Dorret Boomsma, with VU University, Amsterdam; and Chandra Reynolds, with the University of California, Riverside.

Participants in the pilot study, published in advance online in the journal Depression and Anxiety, improved their scores on a standardized measure of anxiety and on a public speaking task after completing two simple exercises twice a week for four weeks.

The hope for CBM is that it can provide a new option for anxiety sufferers who cannot find or pay for a qualified therapist, who are afraid to try cognitive behavior therapies where they directly confront their fears, or who can’t or don’t want to try medications. Still, the idea of computer-based therapy has been controversial, acknowledged Courtney Beard, the new study’s lead author and assistant professor (research) of psychiatry and human behavior in the Warren Alpert Medical School of Brown University.

“A lot of people are skeptical, particularly people like me who are clinicians and know how hard it is to help people with anxiety and how much effort and time it takes in therapy,” Beard said. “It just doesn’t seem possible that a computer program could produce similar effects. But I’m more of a scientist than a clinician so I want to see data.”

Beard’s study is the first randomized clinical trial, albeit with a small sample size of 20 people who received the therapy and 12 placebo controls, to combine two techniques of CBM to treat social anxiety disorder: one that seeks to enhance subjects’ control over what they pay attention to and another that trains them to interpret situations less anxiously.

Beard worked on the study with co-authors Risa Weisberg at Brown and Nader Amir at the University of California–San Diego.

Therapy at the computer

The “attention” technique trains subjects to ignore a worrying social cue and instead to complete a task. Subjects were quickly shown both a disgusted face and a neutral face on a split screen. One face would quickly be replaced with a letter, either an E or an F. The subjects’ task was to report which letter they saw. For those receiving the therapy, the neutral face was always the one replaced, meaning the subjects had to divert their attention from the worrisome disgusted face. For the placebo group, either face had an equal chance of being replaced.

The interpretation technique encourages anxiety sufferers to assign benign interpretations to social situations. Subjects were asked to say whether a word they saw on the screen was related to the sentence that followed. Those receiving the therapy, for instance, would see either “embarrassing” or “funny” before seeing the sentence “People laugh after something you said.” The subjects would be told they were correct if they chose the relatively benign word or incorrect if they chose the anxious interpretation. Placebo subjects, meanwhile, saw words that had nothing to do with the situation’s social nature.

The subjects self-reported their anxiety level five times during the four-week period by answering standard questions on the Liebowitz Social Anxiety Scale. The average score of those receiving the therapy dropped from more than 80 to about 60 (lower is better), while those in the placebo group barely edged down at all. Blinded, trained evaluators judged the public speaking task, a five-minute impromptu speech, at the beginning and the end of the study. The scores showed a significant improvement in those who received the therapy, while the speaking scores of the placebo group got worse.

Studies of CBM began in healthy subjects in 2002, but clinical trials of CBM as a therapy for people with anxiety only began to appear in the literature in 2009, Beard said. Hers is the first clinical trial to add a behavioral performance measure, such as public speaking, and is the first to assess whether patients found the treatment credible (e.g., did the therapy make sense?) and acceptable (was this something you could do?). On both issues, participants provided moderately positive assessments.

Not yet proven

Although the study’s results agree with many of the other small studies published to date, Beard said CBM still must be subjected to larger trials with longer follow-up times before the therapy’s seeming effectiveness can be considered convincing.

Even then, she said, it’s unlikely that CBM would displace other forms of treatment for anxiety disorders. Instead, it might prove worthwhile as a first step to try.

“This certainly isn’t going to replace therapy,” she said. “I see it more as a very inexpensive, very easy to deliver, first-line intervention that could help a lot of people. For those it doesn’t help, then maybe we could devote the more expensive and time-intensive resources to them.”

Funding for the study came from the National Institute of Mental Health. Amir has applied for a patent on CBM technology and is part owner of a company that makes CBM software.

According to author Alexa Tullett, “There’s more than one way to interpret this event. You could see it as an indication that there’s a bad apple in your neighborhood, and in this case you would only feel comforted if that person was arrested. On the other hand, you could see it as an indication that your neighborhood is less safe than you thought, and in this case there would be many things that could ease your concern: getting better locks, starting a community watch program, or having a greater police presence.”

How do you look at this situation? Would you feel relieved if you got safer locks, or would you remain fearful until the robber was taken to jail?

Tullett and her co-authors Rimma Teper, and Michael Inzlicht from the University of Toronto explore the possibility that different threat-reduction approaches can be adaptive in different situations in an article in Perspectives on Psychological Science, a journal of the Association for Psychological Science.

The authors suggest that the way a threat is construed will determine the types of threat-reduction strategies that will be effective for an individual.

In the case of the robbery, Tullett says “the general idea is that if you interpret a threat in a very narrow way, as in a dangerous person is out there, there are limited ways that you can resolve the threat. If, on the other hand, you interpret it broadly, there is a broader range of ways that you can resolve the threat.”

Imagine another scenario – Your friend has overheard his co-workers at work conversing about how he is a nice guy, but not very attractive. You console him, reminding him of his intelligence and accomplishments and are surprised to find that this doesn’t help. This misunderstanding is because you saw this as a threat to your friend’s identity as a desirable person, but your friend saw this as a narrower threat to his identity as an attractive person.

According to the authors, social psychologists have collected a large amount of evidence demonstrating the versatility in how we respond to unexpected and unsettling events.

Author Tullett says there is debate on how we respond to unsettling events. Some believe that when people are unsettled by something that happens in one area of life they wont feel better until they experience a boost in that area. Others disagree, and think that the area doesn’t matter – feeling better in one area makes people feel better in all areas.

This research helps us understand how both of these can be correct depending on how people interpret certain situations – narrowly or broadly.

“Past work has examined the timing of puberty and shown the negative consequences of entering puberty at an early age, but there has been little work done to investigate the effects of tempo,” said Kristine Marceau, a Penn State graduate student and the study’s primary author. “By using a novel statistical tool to simultaneously model the timing and tempo of puberty in children, we present a much more comprehensive picture of what happens during adolescence and why behavior problems may ensue as a result of going through these changes.”

The team — led by Elizabeth Susman, the Jean Phillips Shibley Professor of Biobehavioral Health at Penn State — created a unique nonlinear mixed-effects model that incorporated data from 364 white boys and 373 white girls that had been collected as part of the National Institute of Child Health and Human Development’s Study of Early Child Care and Youth Development, which had an initial goal of determining how variations in the environment are related to children’s development. The data included information about breast and pubic hair development in girls and genital and pubic hair development in boys as assessed by nurses, as well as weight and height for both boys and girls. The data also included information on internalizing and externalizing behavior problems as reported by boys’ and girls’ parents or other caregivers, and risky sexual behaviors as reported by the kids themselves.

“We found that earlier timing for girls was related to a slew of behavior problems, and we also found that a faster tempo of development independently predicted those same sorts of problem behaviors,” said Marceau. “Although timing and tempo both predicted behavior problems in girls, timing and tempo weren’t related to each other. For boys, though, we found a strong relationship between timing and tempo. For example, we found that boys who have later timing combined with slower tempo exhibited the least amount of acting out and externalizing problems.”

The team’s results will appear in the September issue of the journal Developmental Psychology.

Why does going through puberty at a faster rate relate to external behavior problems and internal anxiety and depression?

“The thought is that when the major changes of puberty are compressed into a shorter amount of time, adolescents don’t have enough time to acclimate, so they’re not emotionally or socially ready for all the changes that happen,” said Marceau. “This is the explanation that originally was attributed solely to early timing, but we suggest that the same thing also is happening if the rate of puberty is compressed.”

According to Susman, timing and tempo of puberty vary dramatically across kids. “Children are extremely sensitive to how fast or slow other kids are going through puberty, and that may contribute to both the internalizing depression-type problems or the externalizing problems of acting out,” she said.

In the future, Susman plans to examine the effects of tempo of puberty on later women’s health problems. “One of the things that has concerned me over the years is the relationship between early puberty and later women’s health problems,” she said. “Specifically, there is some indication that early timing of puberty relates to more reproductive cancers, with the speculated mechanism being estradiol. If you’re an early maturer, you have a longer exposure to this hormone. The question is whether the tempo of puberty has similar implications for women’s health.”