Category: Anxiety

Pregnancy among women veterans who served in Iraq and Afghanistan appears to increase their risk for mental health problems such as depression, anxiety, and post-traumatic stress disorder (PTSD), according to a study published in Journal of Women's Health, a peer-reviewed journal published by Mary Ann Liebert, Inc. The paper is available free online.

The stress associated with military service in a war zone may later contribute to an increased risk of mental health problems if a woman veteran becomes pregnant. Because the hormonal and physiological changes that accompany pregnancy can bring on or worsen various mental health conditions it is important to understand what effects military service might have on a pregnant woman's mental health status and how that might affect pregnancy outcomes.

Kristin Mattocks, PhD, Yale University School of Medicine (New Haven, CT), and colleagues from VA Connecticut Healthcare System (West Haven, CT), Indiana University School of Medicine (Indianapolis), and UCLA School of Public Health (Los Angeles, CA), reviewed the records of more than 43,000 women veterans who served in Iraq or Afghanistan and completed their military service between 2001 and 2008. The authors emphasize the importance of identifying and providing appropriate diagnostic and treatment services for this at-risk population in the paper entitled, "Pregnancy and Mental Health Among Women Veterans Returning from Iraq and Afghanistan."

"With the increased number of women serving in the military, it is important that we understand their unique health issues such as mental health problems during pregnancy," says Editor-in-Chief Susan G. Kornstein, MD, Executive Director of the Virginia Commonwealth University Institute for Women's Health, Richmond, VA.

Researchers at the University of Iowa have pinpointed the part of the brain that causes people to experience fear — a discovery that could improve treatment of post-traumatic stress disorder (PTSD) and other anxiety conditions.

Published December 16 in the journal Current Biology, the study investigates how the emotion of fear depends on an almond-shaped brain region called the amygdala. The patient in the case study has a rare condition that destroyed her amygdala. UI researchers observed the patient's response to frightening stimuli such as a haunted house, snakes, spiders, and horror films, and asked her about traumatic experiences in her past — including situations that had endangered her life. They found that without a functioning amygdala, the patient is unable to experience fear.

Studies in the past 50 years have shown the amygdala to play a central role in generating fear reactions in animals from rats to monkeys. This study confirms for the first time that the amygdala is also required for triggering a state of fear in humans. Previous studies with this patient confirmed she cannot recognize fear in facial expressions, but it was unknown until this study if she had the ability to experience fear herself.

Daniel Tranel, Ph.D., UI professor of neurology and psychology and senior study author, said the discovery could lead to new interventions for PTSD and related anxiety disorders. PTSD affects more than 7.7 million Americans, according to the National Institute of Mental Health, and a 2008 analysis by the Rand Corporation predicted that 300,000 soldiers returning from combat in the Middle East would experience PTSD.

"This finding points us to a specific brain area that might underlie PTSD," said Tranel, director of the UI's Interdisciplinary Graduate Program in Neuroscience. "Psychotherapy and medications are the current treatment options for PTSD and could be refined and further developed with the aim of targeting the amygdala."

Justin Feinstein, lead study author and a UI doctoral student studying clinical neuropsychology, says the findings suggest that methods of safely and non-invasively dampening amygdala activity may help people with PTSD.

"This past year, I've been treating veterans returning home from Iraq and Afghanistan who suffer from PTSD. Their lives are marred by fear, and they are oftentimes unable to even leave their home due to the ever-present feeling of danger," Feinstein said. "In striking contrast, the patient in this study is immune to these states of fear and shows no symptoms of post-traumatic stress. The horrors of life are unable to penetrate her emotional core. In essence, traumatic events leave no emotional imprint on her brain."

In examining the role of the amygdala, Feinstein observed and recorded the patient's responses during exposure to snakes and spiders (two of the most commonly feared animals), during a visit to one of the world's scariest haunted houses, and while watching a series of horror films. Feinstein also measured the patient's experience of fear with a large number of standardized questionnaires that probed different aspects of fear, ranging from the fear of death to the fear of public speaking. Additionally, over a three-month period, the patient carried a computerized emotion diary that randomly asked her to rate her current fear level throughout the day.

Across all of the scenarios, the patient failed to experience fear. Moreover, in everyday life, she has encountered numerous traumatic events that have threatened her very existence, yet, by her report, have caused no fear.

"Taken together, these findings suggest that the human amygdala is a pivotal area of the brain for triggering a state of fear," Feinstein said. "While the patient is able to experience other emotions, such as happiness and sadness, she is unable to feel fear. This suggests that the brain is organized in such a way that a specific brain region — the amygdala — is specialized for processing a specific emotion — fear."

For Feinstein and Tranel, the most surprising finding of the study was the patient's behavior when exposed to snakes and spiders. For many years, the patient told the researchers that she hates snakes and spiders and tries to avoid them, yet she immediately started touching them at a pet store, stating that she was overcome with curiosity.

Antonio Damasio, professor of neuroscience at the University of Southern California and a longtime collaborator of Tranel, helped interpret the findings. The researchers say that the results suggest that our fear behavior is often times controlled at a very instinctual, unconscious level.

"Without our amygdala, the alarm in our brain that pushes us to avoid danger is missing," Feinstein said. "The patient approaches the very things she should be avoiding, yet, strikingly, appears to be totally aware of the fact that she should be avoiding these things. It is quite remarkable that she is still alive."

Feinstein and Tranel conducted the study at the UI Department of Neurology. Ralph Adolphs, professor of neuroscience and psychology at the California Institute of Technology, also collaborated on the project. Adolphs has studied fear and the amygdala for many years, in collaboration with Tranel and Damasio.

The National Institutes of Health and a National Science Foundation Graduate Fellowship provided funding for the study.

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Journal Reference:

1. Justin S. Feinstein, Ralph Adolphs, Antonio Damasio and Daniel Tranel. The Human Amygdala and the Induction and Experience of Fear. Current Biology, December 16, 2010 DOI: 10.1016/j.cub.2010.11.042

UC Irvine researchers have identified a novel mechanism in the brain that boosts memory.

In collaboration with scientists at Germany's University of Munster, the UCI team found that a small protein called neuropeptide S can strengthen and prolong memories of everything from negative events to simple objects.

According to study leader Rainer Reinscheid, UCI associate professor of pharmaceutical sciences, the discovery could provide important clues about how the brain stores memories and also lead to new treatments for Alzheimer's disease, dementia and other cognitive impairments.

"Additionally, it may help us better understand post-traumatic stress disorder, which involves exaggerated memories of traumatic events," he said.

In tests on mice, the researchers observed that if neuropeptide S receptors in the brain were activated immediately after a learning experience, it could be recalled for much longer and with much greater intensity.

This memory enhancement lasted up to a week, Reinscheid said, but when NPS receptor activation was disrupted, the mice didn't remember events as strongly — if at all — when tested just a day or two later.

Study results, which appear in a Dec. 8 advance online article for the journal Neuropsychopharmacology, are in accordance with Reinscheid's previous findings that NPS causes wakefulness and has a calming effect.

"It appears that the combination of increased alertness and reduced anxiety produced by NPS prepares the animals to learn much better," he said. "Memory is remarkably improved after activation of their NPS system, and the effects are long-lasting, independent of content."

Naoe Okamura, Celia Garau, Dee Duangdao and Stewart Clark of UCI as well as Kay Jungling and Hans-Christian Pape of the University of Munster contributed to the study, which was funded in part by the National Institute of Mental Health.

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Journal Reference:

1. Naoe Okamura, Celia Garau, Dee M Duangdao, Stewart D Clark, Kay Jüngling, Hans-Christian Pape, Rainer K Reinscheid. Neuropeptide S Enhances Memory During the Consolidation Phase and Interacts with Noradrenergic Systems in the Brain. Neuropsychopharmacology, 2010; DOI: 10.1038/npp.2010.207

 A drug commonly used to treat depression and anxiety disorder was effective at reducing joint and muscle pain associated with a breast cancer treatment, according to a study from the University of Michigan Comprehensive Cancer Center.

The women in the study were taking aromatase inhibitors, a type of drug designed to block the production of estrogen, which fuels some breast cancers. About half of women taking these drugs experience aches and pains in their joints and muscles that cannot be adequately relieved by over-the-counter painkillers. Up to 20 percent of these women will stop taking an aromatase inhibitor because of this pain.

"Since women typically take these drugs for five years, it is important that the side effects not interfere too much with their quality of life, or they will be less likely to continue taking the medicine, which may lead to a greater chance of their breast cancer returning," says study author N. Lynn Henry, M.D., Ph.D., assistant professor of internal medicine at the U-M Medical School.

Henry will present the initial results of the study Dec. 11 at the 33rd Annual San Antonio Breast Cancer Symposium.

The study looked at the drug duloxetine, or Cymbalta, which is used to treat depression and generalized anxiety disorder. It's also been shown to work in multiple other chronic pain conditions, such as fibromyalgia and, more recently, osteoarthritis. It is believed to decrease pain through its actions in the central nervous system.

Of 29 patients evaluated, nearly three-quarters reported that their pain had decreased by at least 30 percent. On average, after eight weeks of treatment, pain scores declined 61 percent. Only one in five patients stopped taking duloxetine because of side effects.

"Duloxetine appears to be effective at reducing the muscle and joint pain many women experience from aromatase inhibitors, with only mild additional side effects," Henry says.

The researchers are planning a randomized, controlled trial comparing duloxetine to placebo. Henry is also doing research looking at the effect of aromatase inhibitors on pain perception to better understand why women develop pain.

Breast cancer statistics: 209,060 Americans will be diagnosed with breast cancer this year and 40,230 will die from the disease, according to the American Cancer Society

Additional U-M authors: Mousumi Banerjee, Ph.D., Dorothy Blossom, Max Wicha, M.D., Catherine Van Poznak, M.D., Jeffrey Smerage, M.D., Ph.D., Anne Schott, M.D., Jennifer Griggs, M.D., M.P.H., and Daniel Hayes, M.D.

Funding: Supported by an Investigator Initiated Grant from Lilly Pharmaceuticals

Patients who need assistance to breathe through mechanical ventilation may benefit from listening to music, a new review published in The Cochrane Library shows. The researchers found that music listening may relax patients, potentially resulting in fewer complications.

Mechanical ventilation often causes major distress and anxiety in patients. The sensation of breathlessness, frequent suctioning, inability to talk, uncertainty regarding surroundings or condition, discomfort, isolation from others, and fear all contribute to high levels of anxiety. Medications administered to reduce anxiety may lead to increased hospital stays and medical costs.

"With all these factors making mechanical ventilation a highly stressful experience, it is exciting that music may provide a way to reduce anxiety in these patients without costly side effects," said lead researcher Joke Bradt of the Department of Creative Arts Therapies at Drexel University in Philadelphia and former researcher at Temple University's Arts and Quality of Life Research Center.

The researchers reviewed data from eight trials involving 213 patients in total. Patients, who had various conditions, including lung disease, cardiac disease and trauma injuries, all received mechanical breathing support via mouth, nose, or tracheotomy (artificial opening in the neck).

In seven trials, patients listened to pre-recorded music and in the remaining trial a trained music therapist provided live music with a tempo matched to the respiratory rate of the patient. On average, listening to music reduced anxiety compared to standard care. It also reduced heart and breathing rates, although not blood pressure.

"These results look promising, but we need more trials to strengthen the evidence and we would certainly be interested in seeing more research on live music interventions provided by trained music therapists," said Bradt. "However, because music listening is an easy treatment to provide, we do recommend that music be offered as a form of stress management for critically ill patients."

Little information was available about the specific kinds of music that produced beneficial effects. "Except for mentioning general styles, such as classical and easy listening, most of the trials made no mention of the music selections used," said Bradt. "In future trials, recording more detailed information about the music would help clinicians make better informed decisions about music selections. We recommend that medical personnel providing music to patients consult with a music therapist to understand what type of music may be best for a particular patient. Likewise, music therapists need to collaborate with medical personnel to carefully monitor the patients' physiological responses to the music."

 We commonly think of sleep as a healing process that melts away the stresses of the day, preparing us to deal with new challenges. Research has also shown that sleep plays a crucial role in the development of memories.

An important component of anxiety disorders, including posttraumatic stress disorder (PTSD), is the formulation of memories associated with fear.

Therefore, researchers decided to evaluate whether sleep deprivation after exposure to an aversive event might eliminate the associated fear, due to the lack of memory consolidation that would typically occur during sleep.

They evaluated healthy volunteers who were shown video clips of both safe driving and unexpected motor vehicle accidents. Half of the volunteers were then deprived of sleep while the other half received a normal night's sleep.

Later testing sessions revealed that sleep deprivation eliminated the fear-associated memories through both fear recognition and physiological fear reactions, suggesting a possible therapy for individuals with PTSD or other anxiety disorders.

Dr. Kenichi Kuriyama, corresponding author, explained: "Sleep deprivation after exposure to a traumatic event, whether intentional or not, may help prevent PTSD. Our findings may help to clarify the functional role of acute insomnia and to develop a prophylactic strategy of sleep restriction for prevention of PTSD."

"It would be nice if the benefits of sleep deprivation upon fear learning could be produced more easily for survivors of extreme stress," noted John Krystal, M.D., Editor of Biological Psychiatry and Professor and Chair of Psychiatry at Yale University. "New insights into the neurobiology of sleep dependent learning may make it possible for these people to take a medication that disrupts this process while leaving restorative elements of sleep intact."

Further research is necessary, but these findings indicate that sleep deprivation is a promising avenue for the possible treatment and prevention of PTSD.

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Journal Reference:

1. Kenichi Kuriyama, Takahiro Soshi, and Yoshiharu Kim. Sleep Deprivation Facilitates Extinction of Implicit Fear Generalization and Physiological Response to Fear. Biological Psychiatry, Volume 68, Number 11

Post-traumatic stress syndrome — when a severely stressful event triggers exaggerated and chronic fear — affects nearly 8 million people in the United States and is hard to treat. In a preclinical study, Northwestern Medicine scientists have for the first time identified the molecular cause of the debilitating condition and prevented it from occurring by injecting calming drugs into the brain within five hours of a traumatic event.

Northwestern researchers discovered the brain becomes overly stimulated after a traumatic event causes an ongoing, frenzied interaction between two brain proteins long after they should have disengaged.

"It's like they keep dancing even after the music stops," explained principal investigator Jelena Radulovic, associate professor of psychiatry and behavioral sciences and Dunbar Scholar at Northwestern University Feinberg School of Medicine. When newly developed research drugs MPEP and MTEP were injected into the hippocampus, the calming drugs ended "the dance."

"We were able to stop the development of exaggerated fear with a simple, single drug treatment and found the window of time we have to intervene," Radulovic said. "Five hours is a huge window to prevent this serious disorder." Past studies have tried to treat the extreme fear responses, after they have already developed, she noted.

The study, conducted with mice, was published Dec. 1 in the journal Biological Psychiatry.

An exaggerated fear disorder can be triggered by combat, an earthquake, a tsunami, rape or any traumatic psychological or physical event.

"People with this syndrome feel danger in everything that surrounds them," Radulovic said. "They are permanently alert and aroused because they expect something bad to happen. They have insomnia; their social and family bonds are severed or strained. They avoid many situations because they are afraid something bad will happen. Even the smallest cues that resemble the traumatic event will trigger a full-blown panic attack."

In a panic attack, a person's heart rate shoots up, they may gasp for breath, sweat profusely and have a feeling of impending death.

Many people bounce back to normal functioning after stressful or dangerous situations have passed. Others may develop an acute stress disorder that goes away after a short period of time. But some go on to develop post-traumatic stress syndrome, which can appear after a time lag.

The stage is set for post-traumatic stress disorder after a stressful event causes a natural flood of glutamate, a neurotransmitter that excites the neurons. The excess glutamate dissipates after 30 minutes, but the neurons remain frenzied. The reason is the glutamate interacts with a second protein (Homer1a), which continues to stimulate the glutamate receptor, even when glutamate is gone.

For the study, Northwestern scientists first subjected mice to a one-hour immobilization, which is distressing to them but not painful. Next, the mice explored the inside of a box and, after they perceived it as safe, received a brief electric shock. Usually after a brief shock in the box, the animals develop normal fear conditioning. If they are returned to the box, they will freeze in fear about 50 percent of the time. However, after the second stressful experience, these mice froze 80 to 90 percent of the time.

The animals' exaggerated chronic fear response continued for at least one month and resembles post-traumatic stress disorder in humans, Radulovic said.

For the second part of the study, Natalie Tronson, a postdoctoral fellow in Radulovic's Dunbar Laboratory for Research on Memory and Fear, and Radulovic repeated the two stressful experiences with the mice but then injected them with MPEP and MTEP five hours after the immobilization. This time the mice did not develop the exaggerated fear response and froze for only 50 percent of the time.

"The mice's fear responses were completely normal," Radulovic said. "Their memories of the stressful event didn't trigger the extreme responses anymore. This means we could have a prevention approach for humans exposed to acute, severe stressful events. "

The research was supported by the National Institute of Mental Health.

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Journal Reference:

1. Natalie C. Tronson, Yomayra F. Guzman, Anita L. Guedea, Kyu Hwan Huh, Can Gao, Martin K. Schwarz, Jelena Radulovic. Metabotropic Glutamate Receptor 5/Homer Interactions Underlie Stress Effects on Fear. Biological Psychiatry, 2010; 68 (11): 1007 DOI: 10.1016/j.biopsych.2010.09.004

The inflammatory bowel disorder Crohn's disease produces its own variant of post traumatic stress (PTSD), indicates research published online in Frontline Gastroenterology.

PTSD creates a vicious circle by worsening the Crohn's symptoms, indicates the study.

Crohn's disease is incurable and can potentially affect the entire digestive tract, producing severe pain and diarrhoea. It is particularly common in Northern Europe, including the UK, and North America.

Its precise cause is not known, but its unpredictability makes it difficult to treat, and treatment is itself expensive, exhausting, and onerous, and carries its own risk of complications, say the authors.

The researchers tracked the health and psychological wellbeing of almost 600 adults over a period of 18 months. All of them had been diagnosed with Crohn's disease and lived in various different locations in Switzerland.

At the start of the study, each patient's mental health was assessed using a 17-item validated PTSD scale, which scores the degree of fear, suffering and impaired quality of life associated with PTSD from 0 to 51.

A score of 15 or more points is suggestive of post traumatic stress disorder, and almost one in five (19%) of the patients achieved this score.

The worsening of symptoms was then monitored during the subsequent 18 months to see if there was any link with the scores and a diagnosis of PSTD.

The results showed that those individuals with PSTD were more than four times as likely to experience worsening symptoms as those who scored below this threshold, and more than 13 times as likely to do so as those scoring zero.

Post traumatic stress occurs in response to traumatic experiences, and is typically manifest in recurring dreams/thoughts, avoidance tactics, irritability and sleeping difficulties.

It is normally associated with violence, emergency situations and natural disasters, but increasingly, research indicates that particular illnesses, such as cancer and HIV infection, plus the diagnostic and treatment procedures that accompany them, also take a hefty emotional toll, say the authors.

They add that over the long term, post traumatic stress permanently changes the body's hormonal and immune responses, so making the sufferer potentially more prone to serious ill health.

"In most cases patients avoid talking about cures which remind them of having the disease…Such behaviour may unwillingly be encouraged by the usual shortness of consultation time and unfamiliarity of [gut specialists] in dealing with the psychological needs of their patients," warn the authors.

Crohn's disease can't be cured, but PTSD can, and doctors should be alert to the psychological fall-out and refer patients for appropriate therapy, they suggest.

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Journal Reference:

1. Rafael J A Cámara, Marie-Louise Gander, Stefan Begré, Roland Von Känel, Swiss Inflammatory Bowel Disease Cohort Study Group. Post-traumatic stress in Crohn's disease and its association with disease activity. Frontline Gastroenterology, 2010; DOI: 10.1136/fg.2010.002733

The heart and the brain appear to be even more closely connected than previously imagined. The damaging effects of myocardial infarction are apparently not confined to the heart, but also affect the brain. In fact, infarction seems to cause neuron loss at the level of the brainstem, which leads to insomnia, notably paradoxical insomnia.

Sleep plays a crucial role in post-infarction remission, as demonstrated by the team of Roger Godbout, Ph.D., his colleague Guy Rousseau and their student Thierno Madjou Bah, investigators at the Research Center of the Hôpital du Sacré-Cœur de Montréal, in a new study published in the scientific journal Sleep.

Although insomnia has long been observed following infarction, to date there have been no studies explaining the phenomenon in scientific terms, apart from the stress that is doubtless brought on by the heart attack. "Thanks to this study, we have been able to show that there is indeed a physiological explanation — the death of cells that play a key role in sleep," says the researcher, who is also a full professor in the Department of Psychiatry at the Université de Montréal.

In the two weeks following a myocardial infarction, not only have periods of paradoxical sleep been observed to be less frequent and of shorter duration, but there are fewer cholinergic neurons in the brainstem, which control paradoxical sleep, due to the phenomenon of self-destruction of cells, known as apoptosis.

Treating insomnia to help the heart heal

A previous study also conducted by the team of Godbout and Rousseau demonstrated that myocardial infarction affected the limbic system, a region of the brain that is responsible for mood, which explains the depression frequently observed after heart attacks. "Since depression is frequently accompanied by insomnia, we wanted to verify whether the neurons in the brainstem were also affected," the investigator explained.

As demonstrated in this study, myocardial infarction, in addition to causing depression, is also associated with the release of factors that provoke the inflammation of tissues, including the brain, and specifically the regions that control sleep, notably the paradoxical sleep phase. The particular function of that phase is to activate regions in the brain that are responsible for integrating our emotions. If that is affected, the risk of depression also increases.

Poor-quality sleep is a known risk factor for cardiovascular disease. Since it can affect remission after an infarction, the risk of complications and recidivism rises and a vicious circle may be set in motion.

Godbout says this study illustrates the importance of rapid intervention in the days following the infarction, before the first signs of insomnia and depression are even apparent. He notes that "any preventive, pharmacological or behavioural treatment is certainly a pathway that should be considered."

The authors of the article Paradoxical sleep insomnia and decreased cholinergic neurons after myocardial infarction in rats, published in SLEEP, are Thierno Madjou Bah, François Laplante, Ron Sullivan, Guy Rousseau and Roger Godbout, researchers at the Research Center of the Hôpital du Sacré-Cœur de Montréal and at the Université de Montréal.

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Journal Reference:

1. Bah TM; Laplante F; Wann BP; Sullivan R; Rousseau G; Godbout R. Paradoxical sleep insomnia and decreased cholinergic neurons after myocardial infarction in rats. Sleep, 2010; 33 (12): 1703-1710 [link]

Have you ever felt uneasy sitting in a doctor's waiting room or climbed the walls waiting for your test results? That feeling of anxious uncertainty can be more stressful than knowing you have a serious illness, according to a study presented November 29 at the annual meeting of the Radiological Society of North America (RSNA).

"Not knowing your diagnosis is a very serious stressor," said the study's lead author, Elvira V. Lang, M.D., associate professor of radiology at Harvard Medical School in Boston, Mass. "It can be as serious as knowing that you have malignant disease or need to undergo a possibly risky treatment."

Dr. Lang and her colleague, Nicole Flory, Ph.D., studied the stress levels of 214 women scheduled to undergo different diagnostic and treatment procedures. Immediately prior to the procedures, each of the women completed four standardized tests measuring stress and anxiety levels: the State Trait Anxiety Inventory (STAI), Impact of Events Scale (IES), Center for Epidemiologic Studies Depression Scale (CES-D) and Perceived Stress Scale (PSS).

Of the 214 women, 112 were awaiting breast biopsy, a diagnostic procedure to investigate a suspicious lump in the breast; 42 were awaiting hepatic chemoembolization, a treatment for liver cancer; and 60 were awaiting uterine fibroid embolization, a treatment for uterine myoma or benign fibroids.

Breast biopsy patients reported significantly higher levels of anxiety, with an average STAI score of 48, than chemoembolization patients, who had an average STAI score of 26, and fibroid embolization patients, with an average STAI score of 24.

IES scores were not significantly different, but were higher among the breast biopsy patients (average score 26) than the other patient groups (average score 23). Average CES-D scores were 15 for breast biopsy patients, 14 for chemoembolization patients and 12 for fibroid embolization patients. PSS ratings were also highest among breast biopsy patients (average rating 18), compared to fibroid embolization patients (16) and chemoembolization patients (15).

"These results really drive the point home that the distress of not knowing your diagnosis is serious," Dr. Lang said. "We believe that healthcare providers and patients are not fully aware of this and may downplay the emotional toll of having a diagnostic exam."

According to Dr. Lang, simple steps can be taken to alleviate patient stress prior to a procedure. "Training the medical team in how to talk to patients makes a huge difference," she said. "This can diffuse tension right away and can help patients to shape expectations in a more helpful fashion."