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The negative effects of stress on cognitive functioning appear to be amplified by a genetic variation associated with Alzheimer’s disease, a new federally funded study has found. The genetic variation may, in effect, accelerate the development of age-related cognitive decline by as much as eight years.
Researchers from the Baltimore Memory Study report in The American Journal of Psychiatry (AJP), the official journal of the American Psychiatric Association, that a high level of the stress hormone cortisol in study participants aged 50 to 70 years was associated with worsened cognitive abilities. The researchers also found that the effect was greater among those with a common form of the gene for apolipoprotein E (APOE), which has been shown to increase the risk for Alzheimer’s disease.
This gene-environment interaction is reported by Brian Lee, M.H.S., Brian Schwartz, M.D., and colleagues at Johns Hopkins University. The group’s findings will be presented online on July 1 under AJP in Advance .
The effect appears to increase as the number of copies of a specific APOE gene in the individual increases. Everyone inherits two versions of the APOE gene, known as alleles - one from each parent. The most common APOE alleles are epsilon-2, -3, and -4. Having at least one epsilon-4 allele increases an individual’s risk of late-onset Alzheimer’s disease. Individuals with two copies of the esiplon-4 version of the gene are particularly susceptible to the damaging effects of cortisol in the brain.
"Our findings indicate that the APOE epsilon-4 allele may increase vulnerability of the aging brain to elevated cortisol levels," said lead author Lee, a doctoral student in epidemiology at the Johns Hopkins Bloomberg School of Public Health. "While our results remain to be replicated, the observed cortisol-APOE interaction is intriguing since both cortisol and APOE have been implicated in cognitive decline associated with aging as well as in Alzheimer’s disease."
The effects on cognitive functioning extended to six of the seven areas that were studied: language, eye-hand coordination, executive functioning, verbal memory/learning, visual memory, and ability to copy a complex visual design.
Buy generic zithromax The deficits are similar in magnitude to those seen with advancing age. The authors estimated the equivalent years of increased age, represented by the poorer cognition of the study participants with high cortisol and the epsilon-4 form of the APOE gene. For language ability, the lower scores of people with high cortisol levels and one epsilon-4 copy were comparable to an age increase of eight years. For those with two epsilon-4 copies, the comparable age increase was even larger.
The study was supported by the National Institute on Aging and the National Institutes of Health Division of Research Resources.
Reference
Lee BK, Glass TA, Wand GS, McAtee MJ, Bandeen-Roche K, Bolla KI, Schwartz BS: Apolipoprotein E Genotype, Cortisol and Cognitive Function in Community-Dwelling Older Adults. Am J Psychiatry (published online July 1, 2008; doi: 10.1176/appi.ajp.2008.07091532)
About the American Journal of Psychiatry
The American Journal of Psychiatry is the official journal of the American Psychiatric Association. Statements in this press release or the articles in the Journal are not official policy statements of the American Psychiatric Association. AJP in Advance is a regular online feature where original research articles accepted for publication in The American Journal of Psychiatry are posted online in advance of their appearance in print.
About the American Psychiatric Association
The American Psychiatric Association is a national medical specialty society whose more than 38,000 physician members specialize in diagnosis, treatment, prevention and research of mental illnesses including substance use disorders. Visit the APA at and
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Researchers from the Cleveland Clinic, Brown University, and Massachusetts General Hospital will present results of a long-term outcome study that builds on previous promising research, which has shown that deep brain stimulation (DBS) is a potentially effective treatment option for people with treatment resistant major depression.
The World Health Organization rates major depression as the top cause of disability worldwide. While many patients with major depression find relief through a combination of psychotherapy and medication, some people are left severely disabled. Patients who are most resistant to medications, psychotherapies, and electroconvulsive therapy (ECT) have little hope of recovery, and suffer a heightened risk of suicide and mortality. Sadly, statistics show that the suicide rate in people with major depression is as high as 15 percent.
DBS surgery involves the placement of tiny implantable electrodes into specific parts of the brain that are functioning abnormally. These electrodes emit tiny pulses of electrical stimulation to block the abnormal activity in the brain, which causes a variety of symptoms such as pain, tremors, movement problems; as well as obsessions, moods and anxieties associated with psychiatric disorders. The success of DBS is dependent on the surgical team’s ability to precisely pinpoint the specific brain area for stimulation. The advantage of DBS is that it is reversible, nondestructive, and can be modified by adjustment of the stimulator settings after implantation.
Ali R. Rezai, MD, director of Cleveland Clinic’s Center for Neurological Restoration, and a multi-center team of investigators were inspired by the success of DBS in treating the tremors associated with Parkinson’s and movement disorders like dystonia and essential tremor. "Starting in 2001, we began treating patients with obsessive compulsive disorder (OCD) with promising outcomes. These findings resulted in the initiation of a subsequent trial for patients with severe and medication intractable major depression, starting in 2003," stated Dr. Rezai.
"The preliminary results of research undertaken between 2003 and 2005 indicated that bilateral DBS of the anterior limb of the internal capsule holds promise for the treatment of intractable major depression, which led to the more extensive research results being presented today," added Dr. Rezai.
The results of the current study, Deep Brain Stimulation for the Treatment of Depression: Long-Term Outcomes from a Prospective Multi-Center Trial, will be presented by Dr. Rezai, from 10:30 to 10:44 a.m. on Tuesday, April 29, 2008, during the 76th Annual Meeting of the American Association of Neurological Surgeons in Chicago. Co-authors are Linda Carpenter, MD, Darin Dougherty, MD, Emad Eskandar, MD, Gerhard Friehs, MD, Cynthia Kubu, PhD, Andre Machado, MD, PhD, Paul Malloy, PhD, Donald Malone, MD, Lawrence H. Price, MD, Steven Rasmussen, MD, Scott Rauch, MD, Stephen Salloway, MD, and Audrey Tyrka, MD, PhD. This multidisciplinary group consists of close collaboration between neurosurgeons, psychiatrists and psychologists from these institutions.
Fifteen chronic and severely depressed patients were enrolled in this study. These patients had failed multiple medication trials, as well as psychotherapy and electroconvulsive therapy (ECT). These highly intractable and often suicidal patients underwent bilateral DBS implantation in the ventral internal capsule/ventral striatum (VC/VS) at the three institutions.
The Montgomery-Asberg Depression Rating Scale (MADRAS) was the primary outcome scale, among many scales, including those assessing overall quality of life, functioning and cognitive status. The outcome raters were blinded to the DBS status of the patient. Follow-up ranged from six to 48 months, with a duration of one year or longer in 11 of the 15 patients. Responder criteria was defined by this study as a 50 percent decrease in MADRAS scores. The following outcomes were noted:
– Responses were seen in seven (47 percent) of 15 patients at six months, five (45.5 percent) of 11 at 12 months, and eight (53.3 percent) of 15 at last follow-up.
– Long-term improvement in depression severity, functioning, and quality of life were all noted.
– Measures of short-term memory improved.
– There were no hemorrhages, infections or other neurological deficits.
"This research substantiates our earlier findings, which indicate that bilateral DBS of the anterior limb of the internal capsule holds promise and hope for select patients suffering from severe and treatment resistant major depression, stated Dr. Rezai. "While about half of this patient group responded to treatment, I feel that as we learn more about this rather new technology, efficacy will continue to improve. It is important to understand that this treatment is not for everyone with major depression and only for those that have tried various medications, psychotherapy and ECT. But, nevertheless, it is very promising news for the many suffering patients and their family members that have virtually given up hope."
Results of the OCD study, Deep Brain Stimulation of the Ventral Internal Capsule/Ventral Striatum for Obsessive-Compulsive Disorder (OCD): World-Wide Experience, will be presented by Dr. Rezai, one day prior to the depression study, 2:45 to 2:59 p.m., Monday, April 28. While OCD is not as prevalent as depression, it does affect 2 to 3 percent of the United States population, and at least 10 percent of patients have disabling cases that are resistant to treatment. The results reveal meaningful symptom reductions and functional improvement in about two-thirds of highly resistant patients after open treatment. Recent improvements in outcomes have been achieved through refinements in targeting areas. This is a worldwide cooperative prospective study involving the largest number of severe and intractable OCD patients with long-term follow-up with DBS.
Founded in 1931 as the Harvey Cushing Society, the American Association of Neurological Surgeons (AANS) is a scientific and educational association with more than 7,200 members worldwide. Buy generic soma The AANS is dedicated to advancing the specialty of neurological surgery in order to provide the highest quality of neurosurgical care to the public. All active members of the AANS are certified by the American Board of Neurological Surgery, the Royal College of Physicians and Surgeons (Neurosurgery) of Canada or the Mexican Council of Neurological Surgery, AC. Neurological surgery is the medical specialty concerned with the prevention, diagnosis, treatment and rehabilitation of disorders that affect the entire nervous system, including the spinal column, spinal cord, brain and peripheral nerves.
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Nearly one in five, or about 300,000, soldiers who has served in Iraq or Afghanistan has post-traumatic stress disorder or major depression — illnesses that could cost the U.S. as much as $6.2 billion over two years in care, lost productivity and lost lives through suicide, according to a RAND report released on Thursday, the Washington Post reports (Scott Tyson, Washington Post, 4/18). The study was based on telephone interviews conducted from August 2007 to January with 1,965 soldiers who have served in Iraq or Afghanistan, in some cases more than once. The soldiers interviewed live in 24 communities with high concentrations of service members, reservists and veterans. Researchers also conducted focus groups. About 1.6 million people have served in Iraq or Afghanistan in the past five years (Alvarez, New York Times, 4/18).
In total, 31% of Iraq and Afghanistan soldiers have experienced a brain injury, stress disorder, or both, the report found. The study found that 19.5% of service members experienced a concussion or other traumatic brain injury during their service (Barnes, Los Angeles Times, 4/18). Of soldiers who reported having a traumatic brain injury, 43% were evaluated by a physician. The report also found that about 7% of soldiers surveyed have a probable brain injury and currently have PTSD. PTSD and major depression were most prevalent in women and reservists, according to the report (Jelinek, AP/Miami Herald, 4/18). The treatment costs for brain injuries have not been determined, but according to the report, based on the number of traumatic brain injury cases diagnosed through June 2007, the cost is expected to be between $600 million and $900 million.
According to the report, the stress of war has resulted in a disproportionately high psychological toll compared with physical injuries. The report warns of "long-term, cascading consequences" for the U.S. if the mental health problems are not treated. Consequences include higher rates of drug use, suicide and unemployment, and increased marital problems (Washington Post, 4/18).
The study was funded by a grant from the Iraq Afghanistan Deployment Impact Fund at the California Community Foundation (Carter, Washington Times, 4/18).
Treatment
The report also found "serious gaps in mental health care," according to the Post. According to the report, 53% of service members with PTSD or depression had sought treatment from a provider in the past year, about half of whom received "minimally adequate" treatment. To care for all of the service members, thousands more certified mental health professionals are needed in both military and civilian sectors, as some veterans are seeking care outside of the Department of Veterans Affairs system because of stigma attached to mental illness, according to the report (Washington Post, 4/18).
Terri Tanielian, one of the study’s authors, said, "When we asked folks what was limiting them from getting the help that they need, among the top barriers that were reported were really negative career repercussions." While the treatment costs might seem high to government officials, failure to treat mental illness could cost the government billions of dollars, according to Lisa Jaycox, another one of the study’s authors. She said, "We make the case that investing in treatment early would prevent some of the negative consequences from unfolding and save money."
Recommendations
The study recommended allowing service members to receive mental health care "off the record," to avoid any possible stigma. Researchers also recommended that fitness-for-duty reports for redeployment not be based on a soldier’s decision to seek mental health care (Los Angeles Times, 4/18). According to Jaycox, Department of Defense Secretary Robert Gates is considering removing a question from security clearance questionnaires about soldiers’ health care history. Col. Loree Sutton, head of the Defense Center of Excellence for Psychological Health and Traumatic Brain Injury, said removing the question would be a "big step forward to help our service members understand that seeking care, in fact, is a sign of strength" (New York Times, 4/18).
Gerald Cross, the VA’s principal deputy undersecretary for health, said VA was increasing outreach to veterans, regardless of whether they reported mental illness. Ira Katz, the VA’s mental health chief, said the VA budget for mental disorders increased from $2 billion in 2001 to $4 billion next year. However, Paul Sullivan, executive director of Veterans for Common Sense, said, "The VA is completely unprepared for the tidal wave," adding, "Unless the VA gets a massive amount of money (and) a set of new strong pro-veteran leaders, the situation will collapse" (Los Angeles Times, 4/18).
The report is available online.
Generic soma pills no prescription CBS’ "Evening News" on Thursday reported on the study. The segment includes comments from Carissa Picard of Military Spouses for Changes, Col. Casper Jones and a soldier diagnosed with PTSD (Dozier, "Evening News," CBS, 4/18). Video of the segment and expanded CBS News coverage are available online.
NBC’s "Nightly News" on Thursday also reported on the study. The segment includes comments from Tanielian and Sutton (Miklaszewski, "Nightly News," NBC, 4/17). Video of the segment is available online.
Reprinted with kind permission from You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at The Kaiser Daily Health Policy Report is published for kaisernetwork.org, a free service of The Henry J. Kaiser Family Foundation© 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.
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A study recommended by David Spiegel of Faculty of 1000 Medicine (), looks at the relationship between depression care management and survival rates in older patients. He identifies it as "an important and well-conducted study of the effects of treatment of depression on survival in a primary care setting"
A leading authority on mind-body interactions and professor of psychiatry and behavioural sciences at Stanford University, Spiegel evaluates the research published in the Annals of Internal Medicine, stressing the finding that "Comorbid depression shortens survival time with cancer, and intervention with medication and psychotherapy can therefore extend survival among cancer patients."
The better survival rates were not seen in patients with depression and cardiovascular disease, only in those with cancer. Spiegel notes that this "is surprising given the well-known link between depression and poor cardiovascular disease outcome".
He concludes, "Vigorous diagnosis and treatment programs for comorbid depression in cancer patients should, based on this study, extend survival time."
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Article adapted by Medical News Today from original press release.
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1 Dr. David Spiegel, Faculty Member for F1000 Medicine Psychiatry Specialty, is a global authority on mind-body interactions and professor of psychiatry and behavioural sciences at Stanford University
2 The effect of a primary care practice-based depression intervention on mortality in older adults: a randomized trial.
Gallo JJ, Bogner HR, Morales KH, Post EP, Lin JY, Bruce ML
Ann Intern Med 2007 May 15 146(10):689-98

3 Faculty of 1000 Medicine’s evaluation of this article is available at
4 Faculty of 1000 Medicine, is a unique online service that helps clinicians and researchers stay informed of high impact articles and access the opinions of global leaders in medicine. Buy synthroid without prescription A distinguished international faculty select and evaluate key articles across medicine, providing a rapidly updated, authoritative guide to the medical literature that matters.
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Researchers at National Jewish Medical and Research Center are conducting trials to evaluate a method to prevent allergic reactions to food. They are feeding peanut- and egg-allergic people increasing doses of an investigational protein extract from the foods to see if they can induce the participants’ immune systems to tolerate the food.
"We hope these trials will lead to the development of the first active, preventive treatment for food allergies," said pediatric allergist David Fleischer, MD, principal investigator for the National Jewish studies. "If successful, it would offer great hope for allergic patients and their families, whose lives are haunted by a daily fear of food."
Currently the only advice doctors can give to the estimated 12 million Americans who have food allergies is to avoid the food and carry a self-injectable dose of epinephrine in case they accidentally consume the allergenic food. There is no treatment available to prevent an allergic reaction to food other than strict avoidance of that food. It can often be difficult to determine if a food contains peanuts or eggs, especially when eating at a restaurant or food prepared by another person. It can even be difficult recognizing egg and peanut proteins listed on food ingredient labels, especially from products that are not manufactured in the U.S. As a result, thousands of people rush to emergency rooms every year suffering severe allergic reactions to food. As many as 200 people die from allergic reactions to food each year.
Allergists treating hay fever and other allergies have long used immunotherapy, also known as allergy shots, to reduce their patients’ sensitivity to pollen, cat and dog dander, and dust mites. However, it is not considered safe to give allergy shots to food-allergic patients because the shots can cause severe allergic reactions. Previous research has suggested that placing the allergenic food protein under the tongue or directly swallowing it, are safer methods of administering food immunotherapy. So that is how National Jewish researchers will try to desensitize allergic patients in the trials.
Study participants (ages 12-40 years for peanut allergy and 6-18 years for egg allergy) will start by consuming tiny amounts of either egg or peanut protein. Physicians and staff at National Jewish will observe them closely to see if they have any symptoms of an allergic reaction. Over the course of several months, participants will consume the protein daily at home, coming in every couple of weeks or so to slowly ramp up the amount of protein they consume until they reach a "maintenance dose."
Buy lasix without prescription Shortly after reaching the maintenance dose, participants will be tested with a larger amount of either egg or peanut to see if the immunotherapy has reduced the immune system’s response. Participants will continue taking the maintenance doses for one to three years to see if they can achieve long-term results. Six to eight weeks after discontinuing the immunotherapy, participants will again consume a larger amount of peanut or egg to see if they have become tolerant of the food.
"In traditional immunotherapy, the majority of hay fever patients achieve tolerance, which can last for years," said Dr. Fleischer, the principal investigator for the National Jewish study. "We hope to achieve similar results for our food allergic patients."
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Article adapted by Medical News Today from original press release.
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National Jewish is participating in this research as part of the Consortium of Food Allergy Research, a network of academic medical centers funded by the National Institute of Allergy and Infectious Diseases. The researchers are all highly experienced food allergists who have conducted thousands of food challenges.
Other participants in the research are the Mount Sinai School of Medicine in New York; John Hopkins University School of Medicine in Baltimore; Duke University School of Medicine in Durham, NC; and the University of Arkansas Children ’s Hospital Research Institute in Little Rock, AR.
Source: William Allstetter
National Jewish Medical and Research Center
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