Teens in child welfare system show higher drug abuse rate

PISCATAWAY, NJ – Teenagers in the child welfare system are at higher-than-average risk of abusing marijuana, inhalants and other drugs, according to a study in the November issue of the Journal of Studies on Alcohol and Drugs. However, the study also shows that parental involvement matters. "When youth perceive that their parents or caregivers are actively engaged in their lives, this may steer them away from drugs," according to lead researcher Danielle L. Fettes, Ph.D., of the University of California, San Diego. "Youth who feel supported by parents tend to have a better sense of self and better mental health and, in this case, are less likely to engage in high-risk behaviors—which is important for this already high-risk population." Using data from two national surveys, Fettes and colleagues found that 18 percent of teens in the welfare system admitted to ever smoking marijuana, versus 14 percent of other teens. Meanwhile, 12 percent said they'd abused inhalants, compared with 6 percent of other U.S. kids. In addition, although abuse of "hard drugs," like cocaine and heroin, was less common, teens in child welfare were still at greater risk: Six percent admitted to ever using the drugs, versus 4 percent of other teens. The findings are not necessarily surprising, according to Fettes. It's known that kids who enter the child welfare system typically have some risk factors for drug use—such as a history of domestic abuse or mental health issues. But until now, there had been little research into their actual rates of substance abuse, Fettes said. For their study, she and her colleagues culled data from two national health surveys: one covered 730 12- to 14-year-olds in the child welfare system; the other included 4,445 kids the same age from the general U.S. population. Overall, teens in the welfare system were more likely to have tried marijuana, inhalants or hard drugs—but not alcohol. Around 40 percent of kids in each survey admitted to drinking at some point in their lives LSW Continuing Education That, according to Fettes, may reflect a couple of facts. "Alcohol is readily available to teenagers," she said, "and drinking is something of a normative behavior to them." But whereas drug use was more common among teens in the welfare system, not all of those kids were at equal risk. A key risk factor—for all teens in the study—was delinquency. Teenagers who admitted to things like shoplifting, theft, running away or using a weapon were at increased risk of both drug and alcohol abuse. On the other hand, some family factors seemed to protect kids from falling into drug use. Teens from two-parent homes were generally less likely to report drug use—and so were kids who said they felt close to their parents or other guardian. For the parents and others who care for these kids, Fettes said it's important to be aware of the increased risk of substance abuse. On the wider scale, Fettes said that right now, there are typically multiple, distinct service systems working with teens in the child welfare system. They may also be receiving mental health services and alcohol and other drug counseling, as well as having contact with the criminal justice system. "Often, they don't work together," she noted. "Given the increased risk, the child welfare system may be an ideal venue to incorporate proven prevention and intervention programs for youth substance use," Fettes concluded. "Drug abuse screening and treatment, or referrals for treatment, should be a regular part of kids' case management." ### Fettes, D. L., Aarons, G. A., & Green, A. E. (November 2013). Higher rates of adolescent substance use in child welfare versus community populations in the United States. Journal of Studies on Alcohol and Drugs, 74(6), 825. To arrange an interview with Danielle L. Fettes, Ph.D., please contact Debra Kain at ddkain@ucsd.edu or 619-543-6202. The Journal of Studies on Alcohol and Drugs is published by the Center of Alcohol Studies at Rutgers, The State University of New Jersey. It is the oldest substance-abuse journal published in the United States. To learn about education and training opportunities for addiction counselors and others at the Rutgers Center of Alcohol Studies, please visit AlcoholStudiesEd.rutgers.edu.

Past weight loss an overlooked factor in disordered eating

PHILADELPHIA (September 24, 2013)— Dieters and weight loss researchers are familiar with the principle: The more weight you've lost, the harder it is to keep it off. A complex and vicious cycle of biological and behavioral factors make it so. But eating disorder research has largely overlooked this influence, and Dr. Michael Lowe, a professor of psychology at Drexel University, has published a flurry of research studies showing that needs to change. "The focus of eating disorder research has very much been on the state of patients' thoughts, beliefs, emotions and personalities," Lowe said. "And while these mental influences are undoubtedly part of the problem, historically there has been very little focus on how their current and past body weights contribute to their eating disorder." Lowe and colleagues' studies – about a dozen on bulimia nervosa have been published in the past several years – show that having an elevated past body weight, and being at a body weight well below highest past weight, may help cause and perpetuate disordered eating. The latest of Lowe's studies was just published in The Journal of Abnormal Psychology, the top journal for eating disorder research, and is the team's first to address this principle in anorexia nervosa. The findings, Lowe says, show that researchers and clinicians need to start taking into account how a person's historical and current body weight contribute to disordered eating. "This fundamentally changes the assumption that the problem is primarily psychological or emotional," Lowe said. The new study, led by doctoral student Laura A. Berner, was based on data collected at the Renfrew Center for eating disorders in Philadelphia, where Lowe is also a consultant. The researchers found that the level of eating disorder symptoms, as well as degree of improvement during treatment, depends on how much weight patients with anorexia nervosa had lost from their previous highest weight (a measure called "weight suppression"), how much they currently weigh and the interaction between the two LSW Continuing Education After controlling for patients' body mass index (BMI, which is a known indicator of disease severity), they found that patients with greater weight suppression had more severe symptoms of anorexia than patients whose low weight was closer to their historical highest weight. Standard measures of disordered eating such as shape concerns, eating concerns, binge eating, depression and menstrual abnormalities were correlated with weight suppression, current BMI, or both. Lowe said that researchers and clinicians who already use weight or BMI as an absolute measure of eating disorder severity should also consider weight suppression as a relative measure. These findings also may have important implications for treatment. "The standards for treating anorexia nervosa are all about 'how much weight do they need to gain to meet a minimally healthy body weight for their height,'" Lowe said. "What we've rarely asked, is 'what is this patient's weight history?'" Lowe said his ongoing research suggests that the answer is that many patients weighed more than their peers before developing anorexia nervosa. "If the patient's body somehow 'remembers' that past higher weight, then even at the minimally healthy body weight she is still going to be struggling mightily to maintain her weight," Lowe said. "That perspective is new. It suggests that future treatments might work toward finding a healthier 'balance point' between what patients once weighed and what they currently weigh." "It is really helpful to have more than one way to look at weight in the eating disorders; we now have evidence that absolute weight and relative weight are both important in predicting difficulties in our work towards full recovery," said Dr. Susan Ice, vice president and chief medical officer of The Renfrew Center. "And it is immensely satisfying to find that science has discovered that there is physical memory or a kind of 'wisdom' in the body." ### Lowe and his research team were recently funded by the National Institute of Mental Health to further investigate the role of these weight-related variables on bulimia nervosa. Individuals with symptoms of bulimia who are interested in participating in this federally funded study may call 215-762-1313 or email TEDS@drexel.edu for additional information. Another research laboratory at Drexel, the Laboratory for Innovations in Health-Related Behavior Change, is recruiting participants who have experienced binge eating problems but do not engage in compensatory behaviors such as self-induced vomiting or laxative use. One project is investigating a new smartphone app for binge eating and the other is evaluating an in-person treatment. Individuals who are interested in participating in these research studies may call 215-762-4900. Paper in the Journal of Abnormal Psychology: http://dx.doi.org/10.1037/a0033930

NAB Unveils Youth Mental Health Awareness Campaign

The National Association of Broadcasters (NAB) launched “OK2TALK,” a campaign to increase understanding and awareness about mental health in youth. The Tumblr-based community campaign includes television and radio ads in English and Spanish that feature teens and young adults opening up about their experiences with mental health. These ads aim to prompt conversation and let people know that help is available and effective. The site also encourages young adults and teens to share their personal stories of recovery, tragedy, struggle, or hope, and includes resources for those seeking help. The “OK2TALK” campaign is inspired in part by the personal struggles of NAB President and former U.S. Senator Gordon Smith’s 22-year-old son, Garrett, who wrestled with depression and ultimately took his own life. One in five Americans experience a mental health issue, yet only one in three reach out to receive mental health services, according to the Centers for Disease Control and Prevention. President Obama called for a national dialogue on mental health, a year-long initiative that will bring together 200 mental health experts, 40 organizations, a dozen members of Congress, and celebrities like Glenn Close and Bradley Cooper to facilitate nationwide discussions about youth and mental health. The White House also launched a website, mentalhealth.gov, with its tag line “Let’s talk about it.” LSW Continuing Education

Study: Use of antipsychotic drugs improves life expectancy for individuals with schizophrenia

Results of a Johns Hopkins study suggest that individuals with schizophrenia are significantly more likely to live longer if they take their antipsychotic drugs on schedule, avoid extremely high doses and also regularly see a mental health professional. Psychiatrists have long known that people with schizophrenia who stick to a drug regimen have fewer of the debilitating delusions and hallucinations that are hallmarks of this illness. But there have been concerns about whether some of the known side effects of the medications — increased risk of cardiovascular disease and diabetes, for example — carry higher mortality risks, the researchers say. "We know that antipsychotic medications reduce symptoms, and our study shows that staying on reasonable, recommended doses is associated with longer life," says Bernadette A. Cullen, M.B., B.Ch., B.A.O., MRCPsych, an assistant professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine, and leader of the study published in Schizophrenia Bulletin. "The same is true for going to see a psychiatrist or therapist," she says, noting that regular visits to a mental health professional are one way to monitor and encourage drug-use compliance, but also in and of themselves increased survival in this vulnerable population. Cullen and her colleagues analyzed data collected between 1994 through 2004 on 2,132 adult Maryland Medicaid beneficiaries with schizophrenia. The researchers reviewed how much medication the patients took, how regularly they took it and how often they visited a mental health professional. The goal of the study was to review how adherence to the 2009 pharmacological Schizophrenia Patient Outcomes Research Team (PORT) guidelines was associated with mortality in this population. Comparing data from year to year, the researchers found that among those patients who had 90 percent or better compliance with their medication schedules, the risk of death was 25 percent lower compared to those who were less than 10 percent compliant. Over the decade-long study period, taking medication did not increase the risk of death and there was a trend towards reducing the mortality rate. In addition, the researchers found that each additional visit per year to a mental health professional was linked to a 5 percent reduction in risk of death overall LSW Continuing Education Cullen's study did not rule out all links between increased mortality and antipsychotic drugs. For example, her team found that people who took high doses of first-generation antipsychotic medication daily (1500 mg or greater chlorpromazine equivalents) were 88 percent more likely to die. She says mortality rates possibly increased in this group because first-generation antipsychotics have been associated with cardiac disease risks, and among those who died while taking the larger doses, 53 percent died of cardiovascular disease. "These drugs work very well, but there is clearly a point of diminishing returns," she says. "You rarely need to be on extremely high doses." Among those whose information was reviewed, the most common cause of death was cardiovascular disease (28 percent); unintended harm, including suicide, was responsible for 8 percent. "If people are taking their medications, they usually have fewer symptoms and are able to be more organized in other areas of their lives," says Cullen, director of community psychiatry at The Johns Hopkins Hospital. "We believe they are then more likely to make appointments with their primary care doctors, to stay on top of other illnesses they may have and to regularly take diabetes, blood pressure or cholesterol medication that they may require to stay healthy. We also believe that they are more likely to be socially engaged and have a healthier lifestyle." "If your illness is under control, you can do a lot more," she adds. Cullen says the study clearly lays out the value of mental health providers to individuals with schizophrenia. Those who saw therapists or psychiatrists were more likely to survive, regardless of whether the individual also took his or her antipsychotic medication on a regular basis, she says. This finding is crucial, she says, given that Maryland Medicaid officials are considering capping the number of mental health visits allowed each year, something the data now suggest is potentially detrimental to survival. Cullen notes that adherence to a medication regimen and moderate first-generation antipsychotic dosing are both part of the 2009 PORT recommendations designed to guide treatment. ### The study was supported by a grant from the National Institutes of Health's National Institute of Mental Health (R01MH074070). Other Johns Hopkins researchers involved in the study include Emma E. McGinty, M.S.; Yiyi Zhang, Ph.D.; Susan dos Reis, Ph.D.; Donald M. Steinwachs, Ph.D.; Eliseo Guallar, M.D., Dr.PH.; and Gail L. Daumit, M.D., M.H.S. For more information: http://www.hopkinsmedicine.org/psychiatry/specialty_areas/community_psych/

Male mice exposed to chronic social stress have anxious female offspring

BOSTON (August 22, 2012) —A study in mice conducted by researchers at Tufts University School of Medicine (TUSM) suggests that a woman's risk of anxiety and dysfunctional social behavior may depend on the experiences of her parents, particularly fathers, when they were young. The study, published online in Biological Psychiatry, suggests that stress caused by chronic social instability during youth contributes to epigenetic changes in sperm cells that can lead to psychiatric disorders in female offspring across multiple generations. "The long-term effects of stress can be pernicious. We first found that adolescent mice exposed to chronic social instability, where the cage composition of mice is constantly changing, exhibited anxious behavior and poor social interactions through adulthood. These changes were especially prominent in female mice," said first author Lorena Saavedra-Rodríguez, Ph.D., postdoctoral fellow in the Larry Feig laboratory at Tufts University School of Medicine (TUSM). The researchers then studied the offspring of these previously-stressed mice and observed that again female, but not male, offspring exhibited elevated anxiety and poor social interactions. Notably, even though the stressed males did not express any of these altered behaviors, they passed on these behaviors to their female offspring after being mated to non-stressed females. Moreover, the male offspring passed on these behaviors to yet another generation of female offspring LSW Continuing Education "We are presently searching for biochemical changes in the sperm of stressed fathers that could account for this newly appreciated form of inheritance" said senior author Larry A. Feig, Ph.D., professor of biochemistry at Tufts University School of Medicine and member of the biochemistry and neuroscience program faculties at the Sackler School of Graduate Biomedical Sciences at Tufts University. "Hopefully, this work will stimulate efforts to determine whether similar phenomena occur in humans." ### This research was supported by award numbers AA019317 from the National Institute on Alcohol Abuse and Alcoholism, and MH083324 from the National Institute of Mental Health, both part of the National Institutes of Health (NIH). The research was also supported by award number NS047243 from National Institute of Neurological Disorders and Stroke (NIH) to the Tufts Center for Neuroscience Research. Saavedra-Rodríguez L, Feig LA. Biological Psychiatry. "Chronic Social Instability Induces Anxiety and Defective Social Interactions Across Generations." Available online August 20, 2012. http://dx.doi.org/10.1016/j.biopsych.2012.06.035 About Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences at Tufts University are international leaders in innovative medical education and advanced research. The School of Medicine and the Sackler School are renowned for excellence in education in general medicine, biomedical sciences, special combined degree programs in business, health management, public health, bioengineering and international relations, as well as basic and clinical research at the cellular and molecular level. Ranked among the top in the nation, the School of Medicine is affiliated with six major teaching hospitals and more than 30 health care facilities. Tufts University School of Medicine and the Sackler School undertake research that is consistently rated among the highest in the nation for its effect on the advancement of medical science.

Researchers pursue red flag for schizophrenia relapse

AUGUSTA, Ga. – Blood levels of a protein that helps regulate inflammation may also serve as a red flag for relapse in some schizophrenia patients, researchers said. "There are no good, objective measures of treatment efficacy or indicators for relapse," said Dr. Brian Miller, a psychiatrist specializing in schizophrenia at the Medical College of Georgia at Georgia Health Sciences University. Researchers hope monitoring levels of interleukin-6 can fill that gap for a population in which more than half of patients don't take their medications as prescribed, often because of side effects. The relapse rate is about 80 percent within two years in patients who don't take their medication properly and about half that in those who do, according to the National Institute of Mental Health LSW Continuing Education "We hope the upshot of our studies will lead to new treatment approaches and strategies for care," Miller said, including the kind of personalized, multi-drug therapies that are becoming the standard for controlling other chronic conditions such as diabetes and hypertension. "We want to attack the disease from as many directions as possible." To get a better handle on how IL-6 levels correspond to disease status, they are looking at levels in blood samples taken multiple times over several years in 305 patients enrolled in a study comparing injectable to oral medication. They also are taking one-time measurements in 80 healthy controls and comparing those to levels in 240 patients who are acutely ill, stable outpatients or stable outpatients who smoke marijuana, a drug commonly abused by patients. While many previous studies have excluded drug abusers, marijuana may increase inflammation, so they want to explore the relationship between IL-6 levels and its use, Miller said. Miller received a five-year, $920,000 National Institute of Mental Health Mentored Patient-Oriented Research Career Development Award to measure IL-6 levels as a potential indicator of how well treatment is working to control disease in these vulnerable patients and whether they are headed to relapse. Amazingly the contributions of "immune disturbances" to schizophrenia have been debated for about 100 years yet anti-inflammatory drugs aren't routinely given to patients in addition to their antipsychotic medication, Miller said. Part of the problem is physicians still have no idea what percentage of patients with this very heterogeneous disease have evidence of increased inflammation. In fact, no two patients have the exact constellation of symptoms considered disease hallmarks, such as hallucinations, delusions, disorganized speech and thinking, he said. But mounting evidence suggests inflammation's impact in schizophrenia. A British study of 50 patients experiencing their first episode of schizophrenic behavior found a handful had indicators of an immune response to their brains, called autoantibodies, and no other conditions, such as a brain infection, to explain them. What amounts to a chronic low-grade flu has been found in some patients and rare immune system disorders such as Sjögren's syndrome, which attacks moisture-producing glands resulting in dry eyes and mouth, also tend to be more common in schizophrenics. Additionally, a handful of clinical trials has shown – not surprisingly – that patients with the highest levels of pro-inflammatory factors had the best response to anti-inflammatory drugs. "It's likely we are talking about a subset of people with this illness who would be most likely to respond to anti-inflammatory therapy – in addition to standard anti-psychotics – so part of our work is to begin to piece out who those people are (and whether) they have a particular clinical picture," Miller said. "Even being able to predict relapse or improve therapy in 25 percent of patients would be a tremendous advance," he said, noting that the vast majority of schizophrenia drugs work essentially by the same mechanism. Once patients can be identified, ideally with a blood test of their IL-6 levels, the next questions are which drugs to use and for how long. Miller's primary mentor for the studies is Dr. Andrew Mellor, a molecular geneticist and immunologist who leads the Cancer Immunology, Inflammation Tolerance Program at the GHSU Cancer Center. Mellor also is Bradley-Turner & Georgia Research Alliance Eminent Scholar in Molecular Immunogenetics. Co-secondary mentors are schizophrenia experts Dr. Peter F. Buckley, Dean of the Medical College of Georgia at GHSU, and Dr. Mark Rapaport, Chair of the Department of Psychiatry and Behavioral Sciences at Emory University School of Medicine. Schizophrenia affects about 1 percent of the population, or some 2.4 million American adults. Hallucinations are a disease hallmark: patients hear voices and can even see, touch and taste things that are not real. They can become depressed, reclusive and suicidal and have an increased risk of cardiovascular and other health conditions. Patients die on average15-20 years younger than the general population. Miller, a recipient of the 2011 National Alliance on Mental Illness Exemplary Psychiatrist Award, said he felt a calling to psychiatry and specifically schizophrenia as a medical student at The Ohio State University. "The patients are wonderful and their stories are fascinating," he said, noting that the field is "wide open" to improve their care. ###

Dual medications for depression increases costs, side effects with no benefit to patients

Taking two medications for depression does not hasten recovery from the condition that affects 19 million Americans each year, researchers at UT Southwestern Medical Center have found in a national study. "Clinicians should not rush to prescribe combinations of antidepressant medications as first-line treatment for patients with major depressive disorder," said Dr. Madhukar H. Trivedi, professor of psychiatry and chief of the division of mood disorders at UT Southwestern and principal investigator of the study, which is available online today and is scheduled for publication in an upcoming issue of the American Journal of Psychiatry. "The clinical implications are very clear – the extra cost and burden of two medications is not worthwhile as a first treatment step," he said. In the Combining Medication to Enhance Depression Outcomes, or CO-MED, study, researchers at 15 sites across the country studied 665 patients ages 18 to 75 with major depressive disorder. Three treatment groups were formed and prescribed antidepressant medications already approved by the Food and Drug Administration. One group received escitalopram (a selective serotonin reuptake inhibitor, or SSRI) and a placebo; the second group received the same SSRI paired with bupropion (a non-tricyclic antidepressant); and a third group took different antidepressants: venlafaxine (a tetracyclic antidepressant) and mirtazapine (a serotonin norepinephrine reuptake inhibitor). The study was conducted from March 2008 through February 2009 LSW Continuing Education After 12 weeks of treatment, remission and response rates were similar across the three groups: 39 percent, 39 percent and 38 percent, respectively, for remission, and about 52 percent in all three groups for response. After seven months of treatment, remission and response rates across the three groups remained similar, but side effects were more frequent in the third group. Only about 33 percent of depressed patients go into remission in the first 12 weeks of treatment with antidepressant medication, as Dr. Trivedi and colleagues previously reported from the Sequenced Treatment Alternatives to Relieve Depression, or STAR*D, study. STAR*D was the largest study ever undertaken on the treatment of major depressive disorder and is considered a benchmark in the field of depression research. That six-year, $33 million study initially included more than 4,000 patients from sites across the country. Dr. Trivedi was a co-principal investigator of STAR*D. The next step, Dr. Trivedi said, is to study biological markers of depression to see if researchers can predict response to antidepressant medication and, thus, improve overall outcomes. ### Other UT Southwestern researchers involved in the study were Drs. Benji Kurian and David Morris, assistant professors of psychiatry; Dr. Diane Warden, associate professor of psychiatry; and Dr. Mustafa Husain, professor of psychiatry, internal medicine, and neurology and neurotherapeutics. Former UT Southwestern professor Dr. A. John Rush, now with the Duke-NUS Graduate Medical School in Singapore, and researchers from the University of Pittsburgh; Massachusetts General Hospital; Columbia University College of Physicians and Surgeons; the University of California, Los Angeles; Vanderbilt University; Harbor-UCLA Medical Center; Virginia Commonwealth University; and Columbia University Medical Center also contributed. The study was funded by the National Institute of Mental Health. Forest Pharmaceuticals, GlaxoSmithKline, Organon and Wyeth Pharmaceuticals provided the medications. Visit http://www.utsouthwestern.org/neurosciences to learn more about UT Southwestern's clinical services in neurosciences, including psychiatry. This news release is available on our World Wide Web home page at www.utsouthwestern.edu/home/news/index.html To automatically receive news releases from UT Southwestern via email, subscribe at www.utsouthwestern.edu/receivenews

Stress about wife's breast cancer can harm a man's health

COLUMBUS, Ohio – Caring for a wife with breast cancer can have a measurable negative effect on men's health, even years after the cancer diagnosis and completion of treatment, according to recent research. Men who reported the highest levels of stress in relation to their wives' cancer were at the highest risk for physical symptoms and weaker immune responses, the study showed. The researchers sought to determine the health effects of a recurrence of breast cancer on patients' male caregivers, but found that how stressed the men were about the cancer had a bigger influence on their health than did the current status of their wives' disease. The findings imply that clinicians caring for breast cancer patients could help their patients by considering the caregivers' health as well, the researchers say. This care could include screening caregivers for stress symptoms and encouraging them to participate in stress management, relaxation or other self-care activities, said Sharla Wells-Di Gregorio, lead author of the study and assistant professor of psychiatry and psychology at Ohio State University. "If you care for the caregiver, your patient gets better care, too," said Kristen Carpenter, a postdoctoral researcher in psychology at Ohio State and a study co-author LSW Continuing Education The research is published in a recent issue of the journal Brain, Behavior and Immunity. Thirty-two men participated in the study, including 16 whose wives had experienced a breast cancer recurrence an average of eight months before the study began and approximately five years after the initial cancer diagnosis. These men were matched with 16 men whose wives' cancers were similar, but who remained disease-free about six years after the initial diagnosis. The participants completed several questionnaires measuring levels of psychological stress related to their wives' cancers, physical symptoms related to stress, and the degree to which fatigue interfered with their daily functioning. Researchers tested their immune function by analyzing white-blood-cell activation in response to three different types of antigens, or substances that prompt the body to produce an immune response. The men's median age was 58 years and they had been married, on average, for 26 years. Almost all of the participants were white. In general, the men whose wives had experienced a recurrence of cancer reported higher levels of stress, greater interference from fatigue and more physical symptoms, such as headaches and abdominal pain, than did men whose wives had remained disease-free. The subjective stress assessment used in the study, called the Impact of Events Scale, measures intrusive experiences and thoughts, as well as attempts to avoid people and places that serve as painful reminders. The scale produces a score between 0 and 75; in this case, the higher the score, the more stressed the men were in relation to their wives' cancer. Overall, the men in the study produced an average score of 17.59. Men whose wives' cancer had recurred scored 26.25 as a group, and men whose wives were disease-free scored 8.94. According to the scale, scores above nine suggest a likely effect from the events, and scores between 26 and 43 indicate an event has had a powerful effect on a person's stress level. Scores over 33 suggest clinically significant distress. "The scores reported here are quite high, substantially higher than we see in our cancer patient samples outside the first year," Carpenter said. "Guilt, depression, fear of loss – all of those things are stressful. And this is not an acute stressor that lasts a few weeks. It's a chronic stress that lasts for years." The participants also reported, on average, a total of approximately seven stress-related physical symptoms. Men with wives with recurrent cancer reported nine symptoms, on average, and those whose wives were disease-free reported fewer than five symptoms, on average. These symptoms varied, but included headaches, gastrointestinal problems, coughing and nausea. When the analysis took into consideration the impact of men's perceived stress in relation to their wives' cancer, higher stress was associated with compromised immune function: Specifically, men with the highest scores on the stress scale also showed the lowest immune responses to two of the three antigens. Previous research has suggested that people with an impaired immune response are more susceptible to infection and might not respond well to vaccines. "Caregivers are called hidden patients because when they go in for appointments with their spouses, very few people ask how the caregiver is doing," said Wells-Di Gregorio, who works in Ohio State's Center for Palliative Care. "These men are experiencing significant distress and physical complaints, but often do not seek medical care for themselves due to their focus on their wives' illness." In these men undergoing chronic stress, the researchers said that it remains unclear whether the immune dysregulation causes more physical symptoms, or stress causes the symptoms and the impaired immune response. Wells-Di Gregorio noted that the stress effect might have been even more pronounced than what they observed because disease-free spouses were more reluctant to participate in the study. "We found that many were not willing to participate because they said they didn't want to think about cancer again," she said. This research was supported by the Ann and Herbert Siegel American Cancer Society Postdoctoral Fellowship, the Longaberger Company-American Cancer Society Grant for Breast Cancer Research, the U.S. Army Medical Research Acquisition Activity Grants, the National Institute of Mental Health and the National Cancer Institute. Co-authors included Caroline Dorfman and Hae-Chung Yang of Ohio State's Department of Psychology; Laura Simonelli of the Christiana Care Health System; and William Carson III of Ohio State's Department of Surgery and Comprehensive Cancer Center