SHY hypothesis explains that sleep is the price we pay for learning

MADISON — Why do animals ranging from fruit flies to humans all need to sleep? After all, sleep disconnects them from their environment, puts them at risk and keeps them from seeking food or mates for large parts of the day. Two leading sleep scientists from the University of Wisconsin School of Medicine and Public Health say that their synaptic homeostasis hypothesis of sleep or "SHY" challenges the theory that sleep strengthens brain connections. The SHY hypothesis, which takes into account years of evidence from human and animal studies, says that sleep is important because it weakens the connections among brain cells to save energy, avoid cellular stress, and maintain the ability of neurons to respond selectively to stimuli. "Sleep is the price the brain must pay for learning and memory," says Dr. Giulio Tononi, of the UW Center for Sleep and Consciousness. "During wake, learning strengthens the synaptic connections throughout the brain, increasing the need for energy and saturating the brain with new information. Sleep allows the brain to reset, helping integrate, newly learned material with consolidated memories, so the brain can begin anew the next day. " Tononi and his co-author Dr. Chiara Cirelli, both professors of psychiatry, explain their hypothesis in a review article in today's issue of the journal Neuron. Their laboratory studies sleep and consciousness in animals ranging from fruit flies to humans; SHY takes into account evidence from molecular, electrophysiological and behavioral studies, as well as from computer simulations. "Synaptic homeostasis" refers to the brain's ability to maintain a balance in the strength of connections within its nerve cells. Why would the brain need to reset? Suppose someone spent the waking hours learning a new skill, such as riding a bike. The circuits involved in learning would be greatly strengthened, but the next day the brain will need to pay attention to learning a new task. Thus, those bike-riding circuits would need to be damped down so they don't interfere with the new day's learning. "Sleep helps the brain renormalize synaptic strength based on a comprehensive sampling of its overall knowledge of the environment," Tononi says, "rather than being biased by the particular inputs of a particular waking day." The reason we don't also forget how to ride a bike after a night's sleep is because those active circuits are damped down less than those that weren't actively involved in learning. Indeed, there is evidence that sleep enhances important features of memory, including acquisition, consolidation, gist extraction, integration and "smart forgetting," which allows the brain to rid itself of the inevitable accumulation of unimportant details. However, one common belief is that sleep helps memory by further strengthening the neural circuits during learning while awake. But Tononi and Cirelli believe that consolidation and integration of memories, as well as the restoration of the ability to learn, all come from the ability of sleep to decrease synaptic strength and enhance signal-to-noise ratios. While the review finds testable evidence for the SHY hypothesis, it also points to open issues. One question is whether the brain could achieve synaptic homeostasis during wake, by having only some circuits engaged, and the rest off-line and thus resetting themselves. Other areas for future research include the specific function of REM sleep (when most dreaming occurs) and the possibly crucial role of sleep during development, a time of intense learning and massive remodeling of brain Counselor CEUs

Alcohol, tobacco, drug use far higher in severely mentally ill

In the largest ever assessment of substance use among people with severe psychiatric illness, researchers at Washington University School of Medicine in St. Louis and the University of Southern California have found that rates of smoking, drinking and drug use are significantly higher among those who have psychotic disorders than among those in the general population. The study is published online in the journal JAMA Psychiatry. The finding is of particular concern because individuals with severe mental illness are more likely to die younger than people without severe psychiatric disorders. "These patients tend to pass away much younger, with estimates ranging from 12 to 25 years earlier than individuals in the general population," said first author Sarah M. Hartz, MD, PhD, assistant professor of psychiatry at Washington University. "They don't die from drug overdoses or commit suicide — the kinds of things you might suspect in severe psychiatric illness. They die from heart disease and cancer, problems caused by chronic alcohol and tobacco use." The study analyzed smoking, drinking and drug use in nearly 20,000 people. That included 9,142 psychiatric patients diagnosed with schizophrenia, bipolar disorder or schizoaffective disorder — an illness characterized by psychotic symptoms such as hallucinations and delusions, and mood disorders such as depression. The investigators also assessed nicotine use, heavy drinking, heavy marijuana use and recreational drug use in more than 10,000 healthy people without mental illness. The researchers found that 30 percent of those with severe psychiatric illness engaged in binge drinking, defined as drinking four servings of alcohol at one time. In comparison, the rate of binge drinking in the general population is 8 percent. Among those with mental illness, more than 75 percent were regular smokers. This compares with 33 percent of those in the control group who smoked regularly. There were similar findings with heavy marijuana use: 50 percent of people with psychotic disorders used marijuana regularly, versus 18 percent in the general population. Half of those with mental illness also used other illicit drugs, while the rate of recreational drug use in the general population is 12 percent. "I take care of a lot of patients with severe mental illness, many of whom are sick enough that they are on disability," said Hartz. "And it's always surprising when I encounter a patient who doesn't smoke or hasn't used drugs or had alcohol problems." Hartz said another striking finding from the study is that once a person develops a psychotic illness, protective factors such as race and gender don't have their typical influence. Previous research indicates that Hispanics and Asians tend to have lower rates of substance abuse than European Americans. The same is true for women, who tend to smoke, drink and use illicit drugs less often than men. "We see protective effects in these subpopulations," Hartz explained. "But once a person has a severe mental illness, that seems to trump everything." That's particularly true, she said, with smoking. During the last few decades, smoking rates have declined in the general population. People over age 50 are much more likely than younger people to have been regular smokers at some point in their lives. For example, about 40 percent of those over 50 used to smoke regularly. Among those under 30, fewer than 20 percent have been regular smokers. But among the mentally ill, the smoking rate is more than 75 percent, regardless of the patient's age. "With public health efforts, we've effectively cut smoking rates in half in healthy people, but in the severely mentally ill, we haven't made a dent at all," she said. Until recently, smoking was permitted in most psychiatric hospitals and mental wards. Hartz believes that many psychiatrists decided that their sickest patients had enough problems without having to worry about quitting smoking, too. There also were concerns about potential dangers from using nicotine-replacement therapy, while continuing to smoke since smoking is so prevalent among the mentally ill. Recent studies, however, have found those concerns were overblown. The question, she said, is whether being more aggressive in trying to curb nicotine, alcohol and substance use in patients with severe psychiatric illness can lengthen their lives. Hartz believes health professionals who treat the mentally ill need to do a better job of trying to get them to stop smoking, drinking and using drugs. "Some studies have shown that although we psychiatrists know that smoking, drinking and substance use are major problems among the mentally ill, we often don't ask our patients about those things," she said. "We can do better, but we also need to develop new strategies because many interventions to reduce smoking, drinking and drug use that have worked in other patient populations don't seem to be very effective in these psychiatric patients." CADC I & II Continuing Education ### Funding for this research comes from the National Institute on Drug Abuse (NIDA), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute of Mental Health (NIMH) and the National Cancer Institute (NCI) of the National Institutes of Health (NIH), and the American Cancer Society. NIH grant numbers R01 DA032843, R01 DA025888, U10 AA008401, UL1 RR024992, P01 CA089392, R01 MH085548, R01 MH085542, K08 DA032680-1, Kl2 RR024994, K01 DA025733. Hartz SM, Pato CN, Medeiros H, Cavazos-Rehg P, Sobell JL, Knowles JA, Bierut LJ, Pato MT and the Genomic Psychiatry Cohort Consortium. JAMA Psychiatry Published online Jan. 1, 2014. doi:10.1001/jamapsychiatry.2013.3276 Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

Anxiety linked to higher long-term risk of stroke

American Heart Association Rapid Access Journal Report The greater your anxiety level, the higher your risk of having a stroke, according to new research published in the American Heart Association journal Stroke. The study is the first in which researchers linked anxiety and stroke independent of other factors such as depression. Anxiety disorders are one of the most prevalent mental health problems. Symptoms include feeling unusually worried, stressed, nervous or tense. Over a 22 year period, researchers studied a nationally representative group of 6,019 people 25-74 years old in the first National Health and Nutrition Examination Survey (NHANES I). Participants underwent an interview and took blood tests, medical examinations and completed psychological questionnaires to gauge anxiety and depression levels. Researchers tracked strokes through hospital or nursing home reports and death certificates. After accounting for other factors, they found that even modest increases in anxiety were associated with greater stroke risk. People in the highest third of anxiety symptoms had a 33 percent higher stroke risk than those with the lowest levels. "Everyone has some anxiety now and then. But when it's elevated and/or chronic, it may have an effect on your vasculature years down the road," said Maya Lambiase, Ph.D., study author and cardiovascular behavioral medicine researcher in the Department of Psychiatry at the University of Pittsburgh School of Medicine, in Pittsburgh, Penn. People with high anxiety levels are more likely to smoke and be physically inactive, possibly explaining part of the anxiety-stroke link. Higher stress hormone levels, heart rate or blood pressure could also be factors, Lambiase said. In earlier work, researchers found that depression was linked to greater risk of stroke. In contrast to anxiety, depression is a persistent feeling of hopelessness, dejection, and lack of energy, among other symptoms. Stroke is the No. 4 killer and a leading cause of disability in the United States Continuing Education for MFTs ### Co-authors are Laura Kubzansky, Ph.D. and Rebecca Thurston, Ph.D. Author disclosures are on the manuscript. The National Heart, Lung, and Blood Institute and the National Institute of Mental Health funded the study. For the latest heart and stroke news, follow us on Twitter: @HeartNews. For stroke science, follow the Stroke journal at @StrokeAHA_ASA. Statements and conclusions of study authors published in American Heart Association scientific journals are solely those of the study authors and do not necessarily reflect the association's policy or position. The association makes no representation or guarantee as to their accuracy or reliability. The association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies) also make donations and fund specific association programs and events. The association has strict policies to prevent these relationships from influencing the science content. Revenues from pharmaceutical and device corporations are available at http://www.heart.org/corporatefunding.

Heavy marijuana users have abnormal brain structure and poor memory

Drug abuse appears to foster brain changes that resemble schizophrenia CHICAGO --- Teens who were heavy marijuana users -- smoking it daily for about three years -- had abnormal changes in their brain structures related to working memory and performed poorly on memory tasks, reports a new Northwestern Medicine® study. A poor working memory predicts poor academic performance and everyday functioning. The brain abnormalities and memory problems were observed during the individuals' early twenties, two years after they stopped smoking marijuana, which could indicate the long-term effects of chronic use. Memory-related structures in their brains appeared to shrink and collapse inward, possibly reflecting a decrease in neurons. The study also shows the marijuana-related brain abnormalities are correlated with a poor working memory performance and look similar to schizophrenia-related brain abnormalities. Over the past decade, Northwestern scientists, along with scientists at other institutions, have shown that changes in brain structure may lead to changes in the way the brain functions. This is the first study to target key brain regions in the deep subcortical gray matter of chronic marijuana users with structural MRI and to correlate abnormalities in these regions with an impaired working memory. Working memory is the ability to remember and process information in the moment and -- if needed -- transfer it to long-term memory. Previous studies have evaluated the effects of marijuana on the cortex, and few have directly compared chronic marijuana use in otherwise healthy individuals and individuals with schizophrenia. The younger the individuals were when they started chronically using marijuana, the more abnormally their brain regions were shaped, the study reports. The findings suggest that these regions related to memory may be more susceptible to the effects of the drug if abuse starts at an earlier age. "The study links the chronic use of marijuana to these concerning brain abnormalities that appear to last for at least a few years after people stop using it," said lead study author Matthew Smith, an assistant research professor in psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine. "With the movement to decriminalize marijuana, we need more research to understand its effect on the brain." Alcoholism and Drug Abuse Counselors Continuing Education The paper will be published Dec. 16 in the journal Schizophrenia Bulletin. In the U.S., marijuana is the most commonly used illicit drug and young adults have the highest -- and growing -- prevalence of use. Decriminalization of the drug may lead to greater use. Because the study results examined one point in time, a longitudinal study is needed to definitively show if marijuana is responsible for the brain changes and memory impairment. It is possible that the abnormal brain structures reveal a pre-existing vulnerability to marijuana abuse. But evidence that the younger a subject started using the drug the greater his brain abnormality indicates marijuana may be the cause, Smith said. The groups in the study started using marijuana daily between 16 to 17 years of age for about three years. At the time of the study, they had been marijuana free for about two years. A total of 97 subjects participated, including matched groups of healthy controls, subjects with a marijuana use disorder, schizophrenia subjects with no history of substance use disorders, and schizophrenia subjects with a marijuana use disorder. The subjects who used marijuana did not abuse any other drugs. Few studies have examined marijuana's effect on the deep regions in the brain -- the 'subcortical gray matter' below the noodle-shaped cortex. The study also is unique in that it looked at the shapes of the striatum, globus pallidus and thalamus, structures in the subcortex that are critical for motivation and working memory. The Marijuana and Schizophrenia Connection Chronic use of marijuana may contribute to changes in brain structure that are associated with having schizophrenia, the Northwestern research shows. Of the 15 marijuana smokers who had schizophrenia in the study, 90 percent started heavily using the drug before they developed the mental disorder. Marijuana abuse has been linked to developing schizophrenia in prior research. "The abuse of popular street drugs, such as marijuana, may have dangerous implications for young people who are developing or have developed mental disorders," said co-senior study author John Csernansky, M.D., chair of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine and Northwestern Memorial Hospital. "This paper is among the first to reveal that the use of marijuana may contribute to the changes in brain structure that have been associated with having schizophrenia." Chronic marijuana use could augment the underlying disease process associated with schizophrenia, Smith noted. "If someone has a family history of schizophrenia, they are increasing their risk of developing schizophrenia if they abuse marijuana," he said. While chronic marijuana smokers and chronic marijuana smokers with schizophrenia both had brain changes related to the drug, subjects with the mental disorder had greater deterioration in the thalamus. That structure is the communication hub of the brain and is critical for learning, memory and communications between brain regions. The brain regions examined in this study also affect motivation, which is already notably impaired in people with schizophrenia. "A tremendous amount of addiction research has focused on brain regions traditionally connected with reward/aversion function, and thus motivation," noted co-senior study author Hans Breiter, M.D., professor of psychiatry and behavioral sciences and director of the Warren Wright Adolescent Center at Feinberg and Northwestern Memorial. "This study very nicely extends the set of regions of concern to include those involved with working memory and higher level cognitive functions necessary for how well you organize your life and can work in society." "If you have schizophrenia and you frequently smoke marijuana, you may be at an increased risk for poor working memory, which predicts your everyday functioning," Smith said. ### The research was supported by grants R01 MH056584 and P50 MH071616 from the National Institute of Mental Health and grants P20 DA026002 and RO1 DA027804 from National Institute of Drug Abuse, all of the National Institutes of Health.

Gene found to be crucial for formation of certain brain circuitry

Identified using new technique that can speed identification of genes, drug candidates Using a powerful gene-hunting technique for the first time in mammalian brain cells, researchers at Johns Hopkins report they have identified a gene involved in building the circuitry that relays signals through the brain. The gene is a likely player in the aging process in the brain, the researchers say. Additionally, in demonstrating the usefulness of the new method, the discovery paves the way for faster progress toward identifying genes involved in complex mental illnesses such as autism and schizophrenia — as well as potential drugs for such conditions. A summary of the study appears in the Dec. 12 issue of Cell Reports. "We have been looking for a way to sift through large numbers of genes at the same time to see whether they affect processes we're interested in," says Richard Huganir, Ph.D., director of the Johns Hopkins University Solomon H. Snyder Department of Neuroscience and a Howard Hughes Medical Institute investigator, who led the study. "By adapting an automated process to neurons, we were able to go through 800 genes to find one needed for forming synapses — connections — among those cells." Although automated gene-sifting techniques have been used in other areas of biology, Huganir notes, many neuroscience studies instead build on existing knowledge to form a hypothesis about an individual gene's role in the brain. Traditionally, researchers then disable or "knock out" the gene in lab-grown cells or animals to test their hypothesis, a time-consuming and laborious process. In this study, Huganir's group worked to test many genes all at once using plastic plates with dozens of small wells. A robot was used to add precise allotments of cells and nutrients to each well, along with molecules designed to knock out one of the cells' genes — a different one for each well. "The big challenge was getting the neurons, which are very sensitive, to function under these automated conditions," says Kamal Sharma, Ph.D., a research associate in Huganir's group. The team used a trial-and-error approach, adjusting how often the nutrient solution was changed and adding a washing step, and eventually coaxed the cells to thrive in the wells. In addition, Sharma says, they fine-tuned an automated microscope used to take pictures of the circuitry that had formed in the wells and calculated the numbers of synapses formed among the cells. The team screened 800 genes in this way and found big differences in the well of cells with a gene called LRP6 knocked out. LRP6 had previously been identified as a player in a biochemical chain of events known as the Wnt pathway, which controls a range of processes in the brain. Interestingly, Sharma says, the team found that LRP6 was only found on a specific kind of synapse known as an excitatory synapse, suggesting that it enables the Wnt pathway to tailor its effects to just one synapse type. "Changes in excitatory synapses are associated with aging, and changes in the Wnt pathway in later life may accelerate aging in general. However, we do not know what changes take place in the synaptic landscape of the aging brain. Our findings raise intriguing questions: Is the Wnt pathway changing that landscape, and if so, how?" says Sharma. "We're interested in learning more about what other proteins LRP6 interacts with, as well as how it acts in different types of brain cells at different developmental stages of circuit development and refinement." Another likely outcome of the study is wider use of the gene-sifting technique, he says, to explore the genetics of complex mental illnesses. The automated method could also be used to easily test the effects on brain cells of a range of molecules and see which might be drug candidates Continuing Education for Social Workers ### Other authors on the paper are Se-Young Choi, now of Seoul National University School of Dentistry; Yong Zhang, Shunyou Long and Min Li of Johns Hopkins University School of Medicine; and Thomas J.F. Nieland, now of the Broad Institute of Harvard and MIT. This work was supported by grants from the Howard Hughes Medical Institute and the National Institute of Mental Health (grant numbers P50MH084020 and 5U54MH084691). Related stories: Gene Found to Foster Synapse Formation in the Brain http://www.hopkinsmedicine.org/news/media/releases/gene_found_to_foster_synapse_formation_in_the_brain Study Refutes Accepted Model of Memory Formation http://www.hopkinsmedicine.org/news/media/releases/study_refutes_accepted_model_of_memory_formation____ Newly Discovered "Switch" Plays Dual Role in Memory Formation http://m.hopkinsmedicine.org/news/media/releases/newly_discovered_switch_plays_dual_role_in_memory_formation

Aging and gene expression -- possible links to autism and schizophrenia in offspring

Advanced paternal age has been associated with greater risk for psychiatric disorders, such as schizophrenia and autism. With an increase in paternal age, there is a greater frequency of certain types of mutations that contribute to these disorders in offspring. Mutations are changes in the genetic code. Recent research, however, looks beyond the genetic code to "epigenetic effects", which do not involve changes in the genes themselves, but rather in how they are expressed to determine one's characteristics. Such epigenetic changes in sperm, related to ageing, have been linked with psychiatric disorders in offspring. Maria Milekic, PhD, reported today, at the American College of Neuropsychopharmacology annual meeting in Hollywood Florida, that old mice have an epigenetic change ‒ a loss of DNA methylation at the locations where the genetic code starts being transcribed. DNA methylation is a biochemical process that plays an important regulatory role in development and disease. The work was done by a research team in the Department of Psychiatry at Columbia University. Offspring of old fathers showed the same deficit in DNA methylation, and they differed in their behavior from the offspring of the young fathers. They showed less exploratory activity and differed in the startle response and in habituation. Two groups, with 10 breeder mice per group, were tested. The breeders were either old (12 month) or young (3 month) males, each bred with two young (3 month) female mice. Then the behavior of the offspring was tested when they were 3 months old. DNA methylation also was tested in the young and old fathers' sperm, and brains of the offspring were tested for DNA methylation as well as gene expression. "We were interested in understanding the mechanism of the paternal age effect", said Dr. Milekic."The risk for schizophrenia increases 2-fold when a father is over 45 years of age, and the risk for autism increases 2-5-fold. It seemed unlikely that mutation alone could account for this. We therefore speculated that DNA methylation could provide an alternative mechanism." Not only did the offspring of the old fathers differ from their counterparts with young fathers in DNA methylation, they also showed significant differences in the expression of genes that have been implicated in autism spectrum disorders and that are known to regulate the development and function of the brain. These findings point to possible factors that can lead to autism spectrum disorders and schizophrenia, and ultimately may lead to more effective therapeutic interventions. With respect to studies in the immediate future, Dr. Milekic said,"We are trying to evaluate changes in different brain regions. Our studies before did not compare brain regions. Most of the genes that have altered expression are in the cerebellum. We are interested in how DNA methylation in the cerebellum is affected by paternal age." Social Worker CEUs ### The work was supported by grants from NIMH and the Simon Foundation to Jay Gingrich, MD, PhD, and a NARSAD Young Investigator Awa rd from the Brain and Behavior Research Foundation to Dr. Milekic.

Mental stress + heart disease: Stronger presence in women under 50

Patients with recent heart attack tested with public speaking task Researchers have found that women younger than 50 with a recent heart attack are more likely to experience restricted blood flow to the heart (myocardial ischemia) in response to psychological stress. The finding may partly explain why younger women who are hospitalized after a heart attack face a greater risk of complications and dying, compared to men of the same age. The results are scheduled to be presented Wednesday, Nov. 20 at the American Heart Association Scientific Sessions meeting in Dallas. Researchers at Emory University have been studying the responses of patients who recently had a heart attack to exercise stress and mental stress, in the form of public speaking on an emotional topic. They have found that women age 50 and below are more likely to experience mental stress-induced ischemia, compared to men of the same age (52 percent compared to 25 percent). The MIMS (Myocardial Infarction and Mental Stress) study included 49 men and 49 women, age-matched pairs who all had a heart attack in the last six months. Their ages ranged from 38 to 59. Among study participants older than 50, there were no significant sex differences in mental stress-induced ischemia;, however, men older than 50 had a rate of exercise-induced ischemia that was twice as high as women of a similar age. "This is the first study to examine the cardiovascular effects of psychological stress as a possible mechanism for the greater mortality after myocardial infarction among younger women," says study leader Viola Vaccarino, MD, PhD, professor and chair of the Department of Epidemiology, Rollins School of Public Health. "We saw a dramatic difference in mental stress-induced ischemia specifically in younger women. In addition, when ischemia was graded in a continuous way, we saw that it was twice as severe among the younger women." Women who experience a heart attack before age 50 are relatively rare, suggesting that perhaps those who do simply have more severe heart disease. However, even when investigators adjusted for different rates of traditional heart disease risk factors such as smoking and diabetes, the disparity remained. In fact, women tended to have less severe coronary artery disease, measured by examining the degree of blockage in their coronary arteries. One possible explanation the Emory investigators considered was a higher burden of psychosocial stress, Vaccarino says. In the study, the younger women were more often poor, of minority race, with a history of sexual abuse and with higher levels of depressive symptoms. "Yet if we look at the statistics, factors such as poverty, race and depression do not explain the difference," she says. "Yes, women have more stressors. But our data show that women also may be more vulnerable to the effects of mental stress on the heart." "This could be an added stimulus to the medical community to pay more attention to the emotional factors in cardiac patients. We are now taking a closer look at potential physiological factors that account for the additional susceptibility in younger women." Emory researchers working with Vaccarino have identified two areas where there are specific differences in younger women who had a recent heart attack: inflammation and heart rate variability, a measure of the responsiveness of the autonomic nervous system. Low heart rate variability has been previously linked to greater heart disease risk. The inflammation data is being presented in a poster by postdoctoral researcher Cherie Rooks, PhD on Sunday, Nov. 17 and the heart rate variability data in a poster by assistant professor Amit Shah, MD on Tuesday, Nov. 19. Interleukin-6 is a marker of inflammation that goes up and down quickly depending on someone's environmental exposures including mental stress, even in healthy individuals. In the MIMS study, women age 50 and below had much higher levels of IL-6 in their blood, compared to age-matched men, both before the mental stress test and afterwards. Women and men older than 50 had similar levels of IL-6. Heart rate goes up in response to physical or psychological stress, but the beats also become more evenly spaced. Heart rate variability is a measure of how much moment-to-moment fluctuation is present; higher heart rate variability is a marker of a more flexible, and thus healthier, autonomic system. In the MIMS study, younger women had their heart rate variability dip more in response to stress, compared to men the same age. This is additional evidence that young women after a heart attack may be more vulnerable to the adverse effects of psychological stress on the heart. Vaccarino and her colleagues are continuing to investigate mental stress-induced ischemia, including how it affects mortality and complication rates, in a second phase of the MIMS study at Emory, which will include a larger sample with patient follow-up Alcoholism and Drug Abuse Counselors Continuing Education ### How the study was conducted The mental stress test part of the study was a public speaking task involving an emotional topic. Participants were asked to imagine a real-life stressful situation, such as a close relative been mistreated in a nursing home. They had to quickly prepare a speech and deliver it in front of a video camera and an audience wearing white coats, while their blood pressure and other vital signs were monitored. Immediately afterwards, cardiac imaging was performed to assess blood flow within the heart via SPECT (single photon emission computed tomography). On a separate day, study participants performed a standard exercise test on a treadmill; a few were unable to exercise at a high heart rate and had to have a "pharmacological" stress test with a drug that dilates coronary arteries. The research was supported by the National Heart Lung and Blood Institute and the National Institute for Mental Health (R21HL093665, R21HL093665-01A1S1, R01 HL109413, K24HL077506, and K24 MH076955).