Category: Depression

Nearly ten percent of all cases of depression are so severe that the patients do not respond to any established treatment method. Targeted stimulation of areas in the brain using a type of "brain pacemaker" has recently raised hopes: According to initial studies, half of patients with the most severe depression treated in this manner see a significant improvement in mood. Physicians from the University of Bonn, together with colleagues from the US, have suggested a new target structure for deep brain stimulation (as it is technically called). They hope to achieve an even better success rate with fewer side effects.

The work has been published in the journal Neuroscience and Biobehavioral Reviews.

In deep brain stimulation, physicians implant electrodes in the brain. Using an electrical pacemaker implanted under the patient's clavicle, physicians can influence the function of certain areas of the brain in a lasting manner. The method was originally developed for treating patients with Parkinson's disease, in order to alleviate the typical movement problems.

Lasting Improvement

For several years, the method has also been investigated in the treatment of the most severe cases of depression, with striking and completely unexpected success: In patients who had undergone many years of unsuccessful treatment, the symptoms sometimes significantly resolved. The most striking aspect: "Depression does not return in patients who responded to the stimulation," emphasizes Professor Dr. Thomas Schläpfer from the Bonn Hospital for Psychiatry and Psychotherapy. "The method appears to have lasting effects — and this is in the case of the most treatment-resistant patient group described in the literature. This has never before happened."

Deep brain stimulation has been tested to date in three different areas of the brain: the nucleus accumbens, the internal capsule, and a structure known as cg25. Surprisingly, the effects are nearly identical — regardless of which of these centers the physicians stimulate. Together with colleagues from Baltimore and Washington, the Bonn researchers have since been able to explain why this is the case: Using a novel tomography method, they were able to make the "cable system" of the three brain centers visible. "In doing this, we determined that at least two of these three areas — probably even all three — are attached to one and the same cable harness," explains the Bonn brain surgeon, Professor Dr. Volker Coenen.

This is the so-called medial forebrain bundle, a structure which has been known in animals for a long time. The forebrain bundle forms a kind of feedback loop which allows us to anticipate positive experiences. "This circuit motivates us to take action," says Coenen. "In patients with depression, it is apparently disrupted. This results in, among other things, an extreme lack of drive — a characteristic symptom of the disease."

The nucleus accumbens, internal capsule, und cg25 all appear to be connected to the medial forebrain bundle — rather like leaves are connected to the branch from which they arise. Whoever stimulates one of these regions of the brain simultaneously influences the other components of the motivation circuit to a certain extent. Coenen, who was the first to anatomically describe the forebrain bundle in humans, now proposes implanting the electrode for deep brain stimulation directly into this structure. "We would use the electrode to send the current pulses to the base of the network and not to the periphery, as before," explains Schläpfer. "We could thus potentially work with lower currents and yet achieve greater success."

A comparatively low-risk procedure

Observations of patients with Parkinson's disease appear to support this idea: in this case, a network of brain structures responsible for movements is stimulated. The more basally (figuratively speaking: near the branch) the electrical stimulation is applied, the greater its effect. At the same time, the risk of adverse side effects is reduced.

By now, more than 80,000 patients with Parkinson's disease worldwide have a brain pacemaker in their body. "Experiences to date demonstrate that the brain intervention necessary for this is relatively low-risk," stresses Professor Coenen. "Thus from a medical point of view, there is nothing that argues against also using this method to help people with very severe depression."

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Journal Reference:

1. Volker A. Coenen, Thomas E. Schlaepfer, Burkhard Maedler, Jaak Panksepp. Cross-species affective functions of the medial forebrain bundle—Implications for the treatment of affective pain and depression in humans☆. Neuroscience & Biobehavioral Reviews, 2010; DOI: 10.1016/j.neubiorev.2010.12.009

Older patients with diabetes who are not dealing well with the disease are likely to have symptoms of depression, and spouses of older patients also suffer distress related to diabetes and its management, according to research from Purdue University.

"Responsibilities and anxieties can differ for patients with diabetes and their spouses, but each may experience stress, frustration and sadness at times related to the demands of living with this disease," said Melissa M. Franks, an assistant professor of child development and family studies. "We know spouses often support their partners, but in our work we want to know what form their involvement takes and how the disease and its management affect both the patient and spouse."

Franks and her team found that the distress spouses feel is similar to what patients feel, and this could contribute to their own depressive symptoms such as irritability or sadness. These depressive symptoms come from their own anxieties about living with the disease or caring for someone with the disease and not necessarily because the other person is struggling.

Researchers also found that when male patients were concerned about the management of their diabetes, their depressive symptoms were elevated more than those for female patients with similar levels of concerns.

"This gender difference is consistent with prior work showing that male patients who are not managing their disease well tend to experience greater depressive symptoms," Franks said. "And while we saw this difference between male and female patients, we did not see the same pattern of distress between their respective spouses. This is surprising, because one might assume that the spouse would be as worried, or, according to family roles, that wives might worry more. However, more research, especially long-term observations, is needed."

The findings, based on statistical models with 185 couples older than 50, appeared in the December issue of the Family Relations journal. The patients and spouses completed individual surveys that measured distress related to diabetes, such as adherence to treatment recommendations, as well as depressive symptoms. The gender effects were measured by comparing the couples' responses. There were 67 female patients and 118 male patients, and each couple was screened to make sure only one person had diabetes.

"Because spouses' distress is not always directly linked to feelings of their partner, it tells us that we need to pay more attention to the spouse as well as the patient," she said. "Understanding the triggers for depressive symptoms can help practitioners and experts better care for patients and spouses as individuals and as a unit.

"We also found that many people reported some depressive symptoms, and some reported levels indicative of risk for clinical depression. It's important to consider depressive symptoms because they may signal concerns and problems that could be alleviated with treatment."

Diabetes affects about one in five Americans over the age of 60, and the majority of those people have Type 2 diabetes, which is a disease of the endocrine system. Type 2 diabetes, also referred to as adult-onset diabetes, is caused by insufficient secretion of insulin and resistance to insulin, which is problematic because it lessens the ability of cells to absorb glucose from the bloodstream. The incidence of the disease, which is considered a leading cause of death, is increasing as more people are overweight and sedentary.

The disease is managed daily through diet, exercise and medications. Complications, such as poor blood circulation, vision impairment, heart disease and stroke, are possible if the disease is not managed. In this study, spouses often reported that the disease's daily management as well as the fear of their loved one's living with diabetes were common concerns.

Franks co-authored the study with Todd Lucas from Wayne State University, Mary Ann Parris Stephens from Kent State University, Karen S. Rook from the University of California at Irvine and Richard Gonzalez at University of Michigan.

This work was funded by the National Institute on Aging and the Kent State University-Summa Health System Center for the Treatment and Study of Traumatic Stress. Franks' future studies will look at diet management in the context of distress and depression for patients and their spouses.

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Journal Reference:

1. Melissa M. Franks, Todd Lucas, Mary Ann Parris Stephens, Karen S. Rook, Richard Gonzalez. Diabetes Distress and Depressive Symptoms: A Dyadic Investigation of Older Patients and Their Spouses. Family Relations, 2010; 59 (5): 599 DOI: 10.1111/j.1741-3729.2010.00626.

 A recent study confirmed that low socioeconomic status (SES) is associated with higher risk of depressive symptoms in patients with rheumatoid arthritis (RA). Statistically significant differences in race, public versus tertiary-care hospital, disability and medications were found between depressed and non-depressed patients.

Study findings are reported in the February issue of Arthritis Care & Research, a journal published by Wiley-Blackwell on behalf of the American College of Rheumatology (ACR).

Roughly 1.3 million Americans are affected by RA — a chronic autoimmune disease that can cause functional limitations and may lead to physical disability in many patients. Prior studies have shown that depression is common, occurring in 13% to 42% of RA patients and is associated with worse outcomes, including greater risk of heart attack, suicide, and death. In the U.S., socioeconomic position as measured by race, gender, age, income, education and health access has significant impact on overall health.

Mary Margaretten, M.D., from the Arthritis Research Group at the University of California, San Francisco (UCSF) and lead study author explained, "We assessed the extent to which low SES influences the relationship between disability and depression in order to better identify those patients at higher risk for depression." Researchers used data obtained from the UCSF RA cohort in which participants were enrolled from an urban county, public hospital that serves the poor and a referral, tertiary-care medical center. The data included 824 visits for 466 patients, 223 from the public hospital and 243 from the tertiary-care clinic.

Analysis showed that 37% of participants had moderate to severe depression, scoring 10 or higher on the Patient Health Questionnaire (PHQ-9). The mean Health Assessment Questionnaire (HAQ) score was 1.2 and the disease activity score (DAS28) was 4, indicating fairly high levels of functional impairment and disease activity, respectively. Researchers also found significant differences between depressed and non-depressed patients related to race, public versus university hospital, functional limitation and disease modifying anti-rheumatic drug (DMARD) treatment. Differences in depression severity were not impacted by gender, age, disease duration, steroid use and dose, or biologic therapy.

Furthermore, the team found that county hospital patients also had significantly higher depression scores (PHQ-9 of 7.3) than patients at the university medical center (PHQ-9 of 5.7). An interaction existed between socioeconomic status and disability such that the association of functional limitation with depression scores was stronger for patients at the public hospital clinic compared to those at the tertiary-care clinic.

Dr. Margaretten concluded, "For the same level of disability, patients with low SES may be more likely to experience depression. Detection and documentation of the differing effects of disability on depression between patients of different socioeconomic status can help rheumatologists improve health outcomes by initiating appropriate and timely treatment for depression."

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Journal Reference:

1. M. Margaretten, J. Barton, L. Julian, P. Katz, L. Trupin, C. Tonner, J. Graf, J. Imboden, E. Yelin. Socioeconomic determinants of disability and depression in patients with rheumatoid arthritis. Arthritis Care & Research, 2010; DOI: 10.1002/acr.20345

Pioneering neurosurgical treatment, which very accurately targets brain networks involved in depression, could help people who suffer with severe and intractable depression.

The research led by Dr Andrea Malizia, Consultant Senior Lecturer in the School of Social and Community Medicine at the University of Bristol and Mr Nikunj Patel, Senior Clinical Lecturer in the Department of Neurosurgery at North Bristol NHS Trust, are pioneering a number of treatments including experimental antidepressants, deep brain stimulation (DBS) and stereotactic neurosurgery.

The patient, whose illness had stopped responding to conventional treatments, was offered DBS in the first trial in the world that stimulates two different brain networks that are involved in depression. DBS in this case provided some temporary response but was not sufficient to make her well. She is now well following further advanced stereotactic neurosurgery carried out in early 2010.

Deep brain stimulation consists of inserting thin wires in the brain that are connected to a 'pacemaker'. The effects are to inhibit and stimulate brain circuits that re specific to the condition being treated. The current DBS trial targets different circuits involved in depression. These monitor the regulation of emotion, oversee the integration of emotion with bodily and intellectual function and regulate internal drives.

Some patients do not respond to DBS or are not suitable for it, in which case the option of an 'Anterior Cingulotomy' using implantable guide tubes (GTAC) has been specifically developed in Frenchay and this patient was the first to have it. This operation also modifies circuits that are important in emotion and the academics believe to be overactive in a number of psychiatric disorders. The neurosurgical developments pioneered at Frenchay make the surgery much more accurate and hopefully this will have an impact on increasing efficacy and decreasing side effects.

Dr Malizia said: "Our patients and their families suffer enormously and it is often thought that nothing else can be done. This lady responded temporarily to two of the complex treatments that we initiated in Bristol, but in the end remission has only been achieved by persisting and moving on to the next advanced treatment.

"We are very grateful to our patients and their relatives who, in spite of depression destroying their lives, bravely carry on fighting the illness year after year, and also to the League of Friends at Frenchay hospital who have donated DBS equipment — their support has been essential in starting this important endeavour."

Depression is an illness that affects about 20 per cent of people at least once in their lifetime. About half the people get well within six months but about ten per cent of sufferers are still unwell after three years. From then on the proportion of people who get well is much reduced with only about one in ten getting better every year.

There are a number of conventional treatments for depression including specific psychotherapies, different antidepressant medicines and electroconvulsive therapy (ECT). Long-term experience has shown that each time a medical treatment does not work, there is a decrease in the probability of the next treatment working of about a third. This means that although 60 per cent of patients respond to the first antidepressant, only about 10 per cent will respond to the fifth. ECT remains the most efficacious short-term treatment but it does not work for everyone, its effects can be short lasting and some people have considerable side effects.

People who experience chronic depression can be very severely disabled: many lose their jobs, are on benefits, have to change home or lose their family. Personal distress is high and about 15 per cent die by suicide.

The Psychopharmacology and Functional Neurosurgery Service in Bristol provides complex treatments for these severely disabled people and aims to understand the brain changes underlying this disorder by using advanced brain imaging techniques and sleep recordings.

Healthcare workers can most directly affect quality of life (QOL) of patients with advanced stage lung cancer by helping manage symptoms such as pain, lack of energy, shortness of breath, coughing, difficulty sleeping and dry mouth, according to a study recently published in the journal Oncology Nursing Forum.

Understanding the symptoms, particularly symptom distress — or the degree to which a symptom bothers a person, is crucial to improved patient care. Intervention at the time of diagnosis is important because patients with stage IIIb or IV lung cancer may approach the end of life quickly.

The study, "Determinants of Quality of Life in Patients Near the End of Life: A Longitudinal Perspective" was conducted by Carla Hermann, PhD, RN, associate professor, University of Louisville School of Nursing, and Stephen Looney, PhD, Medical College of Georgia.

The researchers interviewed 80 patients with either stage IIIb or IV lung cancer who were newly diagnosed or had recurrent lung cancer. The study measured symptom frequency, severity, and distress; functional status; anxiety and depression. Within five months of diagnosis, 40 patients had died. The strongest determinant of QOL was symptom distress, followed by symptom severity, symptom frequency and depression.

"People at the end of life have a wide variety of needs, and healthcare workers need to evaluate patients holistically — focusing not only on physical needs but also on their psycho-social and spiritual needs," Hermann said. "The end of life can be a time of great personal growth for many, and nurses and other healthcare professionals can help foster that growth."

The implication of this research for nurses and other healthcare workers is to develop a thorough symptom assessment and to intervene quickly for patients with advanced lung cancer.

Nurses and other healthcare professionals have a unique opportunity to make a valuable and lasting impact on patients and their families, Hermann concluded.

The research was funded by a grant from the National Institute of Nursing Research of the National Institutes of Health.

As many as one in 16 surgeons reported having suicidal thoughts in the previous year, but few sought help from a mental health clinician, according to a report in the January issue of Archives of Surgery, one of the JAMA/Archives journals.

Death from suicide is more common among physicians than among the general population or among other professionals, according to background information in the article. "Although suicide is strongly linked to depression, the lifetime risk of depression among physicians is similar to that of the general U.S. population," the authors write. "This observation suggests that other factors may contribute to the increased risk of suicide among physicians. Access to lethal medications and knowledge of how to use them has been suggested as one factor; however, the influence of professional characteristics and forms of distress other than depression (e.g., burnout) are largely unexplored."

Tait D. Shanafelt, M.D., of Mayo Clinic, Rochester, Minn., and colleagues surveyed members of the American College of Surgeons in 2008. The anonymous survey included questions regarding suicidal ideation (thoughts or plans of suicide) and the use of mental health resources, a depression screening tool and assessments of burnout and quality of life.

Of 7,905 participating surgeons (a response rate of 31.7 percent), 501 (6.3 percent) reported thoughts of suicide during the previous year. Older surgeons were more likely to report suicidal thoughts — surgeons age 45 and older had 1.5 to three times the rate of suicidal ideation of the general population. Being married and having children were associated with a lower likelihood of suicidal thoughts, and the risk was higher among those who had been divorced.

"The perception of having made a major medical error in the previous three months was associated with a three-fold increased risk of suicidal ideation, with 16.2 percent of surgeons who reported a recent major error experiencing suicidal ideation compared with 5.4 percent of surgeons not reporting an error," the authors write. Suicidal thoughts were also strongly associated with distress, depression and with all three domains of burnout: emotional exhaustion, depersonalization and low personal accomplishment.

Of the surgeons with suicidal thoughts, 130 (26 percent) sought help from a psychiatrist or psychologist, whereas 301 (60.1 percent) were reluctant to do so because it might affect their medical license. Among the 461 surgeons (5.8 percent) who had used antidepressant medications within the past year, 41 (8.9 percent) had self-prescribed and 34 (7.4 percent) had received the prescription from a friend who was not formally caring for them as a patient.

Reluctance to seek care is likely reinforced by the fact that 80 percent of state medical boards inquire about mental illness on initial licensure applications and 47 percent do so on renewal applications. However, many focus not on whether a mental health condition is present but whether it is an impairment, the authors note.

"Additional studies are needed to evaluate the unique factors that contribute to the higher rate of suicidal ideation among surgeons in conjunction with efforts to reduce surgeons' distress and eliminate barriers that lead to underuse of mental health resources," they conclude.

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Journal Reference:

1. Tait D. Shanafelt; Charles M. Balch; Lotte Dyrbye; Gerald Bechamps; Tom Russell; Daniel Satele; Teresa Rummans; Karen Swartz; Paul J. Novotny; Jeff Sloan; Michael R. Oreskovich. Special Report: Suicidal Ideation Among American Surgeons. Archives of Surgery, 2011; 146 (1): 54-62 DOI: 10.1001/archsurg.2010.292

One out of every four or five students who visits a university health center for a routine cold or sore throat turns out to be depressed, but most centers miss the opportunity to identify these students because they don't screen for depression, according to new Northwestern Medicine research.

About 2 to 3 percent of these depressed students have had suicidal thoughts or are considering suicide, the study found.

"Depression screening is easy to do, we know it works, and it can save lives," said Michael Fleming, professor of family and community medicine at Northwestern University Feinberg School of Medicine. "It should be done for every student who walks into a health center."

The consequences of not finding and treating these students can be can be serious and even deadly. "These kids might drop out of school because they are so sad or hurt or kill themselves by drinking too much or taking drugs," Fleming said.

"Things continually happen to students — a low grade or problems with a boyfriend or girlfriend — that can trigger depression," Fleming said. "If you don't take the opportunity to screen at every visit, you are going to miss these kids."

Fleming, who joined Feinberg in the fall of 2010, is lead author of a paper on the findings in the January issue of the American Journal of Orthopsychiatry. He conducted the research when he was a faculty member at the University of Wisconsin.

The study is the first to screen for depression in a large population of students who are coming to campus health centers for routine care. Prior depression studies have been conducted by surveying general college samples or students in counseling centers. The frequency of depression and suicidal thoughts among campus health clinic users was nearly twice as high as rates reported in general college samples.

Depressed students need treatment, which may include counseling and medication. These students are more likely to drink, smoke and be involved in intimate partner violence, the study found.

With new technology, screening students is simple, Fleming noted. While waiting for an appointment at the health center, the student could answer seven simple questions — a depression screening tool that that could be immediately entered into his electronic health record. "They can answer those seven questions in a minute," Fleming said.

When the doctor or nurse sees the student, she then could address the student's sadness or depression.

Universities typically separate mental health treatment from primary care treatment. If a student comes to a campus health center and complains about depression, he is referred to a counseling center.

"But students don't necessarily get there unless they are pretty depressed," Fleming said. "If we screen, we can try to find every student that is depressed."

Historical perceptions and biases against preventive screenings are that kids who need treatment the most don't go to campus health centers, and they won't tell the truth about their depression.

That's wrong. "Students will tell you the truth," Fleming said. "If they are sad and depressed, they will tell you that. And, kids who are drinking too much or who are suicidal do go to the campus health centers."

The study also found that students who exercise frequently are not as depressed. "That's the one thing that seemed to be protective," Fleming said.

The study surveyed 1,622 college students at college campuses including the University of Wisconsin, the University of Washington and the University of British Columbia.

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Journal Reference:

1. Sara Mackenzie, Jennifer R. Wiegel, Marlon Mundt, David Brown, Elizabeth Saewyc, Eric Heiligenstein, Brian Harahan, Michael Fleming. Depression and Suicide Ideation Among Students Accessing Campus Health Care. American Journal of Orthopsychiatry, 2011; 81 (1): 101 DOI: 10.1111/j.1939-0025.2010.01077.x

Depression and diabetes appear to be associated with a significantly increased risk of death from heart disease and risk of death from all causes over a six-year period for women, according to a report in the January issue of Archives of General Psychiatry, one of the JAMA/Archives journals.

Depression affects close to 15 million U.S. adults each year and more than 23.5 million U.S. adults have diabetes, according to background information in the article. Symptoms of depression affect between one-fifth and one-fourth of patients with diabetes, nearly twice as many as individuals without diabetes. Diabetes and its complications are leading causes of death around the world.

An Pan, Ph.D., of the Harvard School of Public Health, Boston, and colleagues studied 78,282 women aged 54 to 79 in 2000 who were participating in the Nurses' Health Study. The women were classified as having depression if they reported being diagnosed with the condition, were treated with antidepressant medications or scored high on an index measuring depressive symptoms. Reports of type 2 diabetes were confirmed using a supplementary questionnaire.

During six years of follow-up, 4,654 of the women died, including 979 who died from cardiovascular disease. Compared with women who did not have either condition, those with depression had a 44 percent increased risk of death, those with diabetes had a 35 percent increased risk of death and those with both conditions had approximately twice the risk of death.

When considering only deaths from cardiovascular disease, women with diabetes had a 67 percent increased risk, women with depression had a 37 percent increased risk and women with both had a 2.7-fold increased risk.

"The underlying mechanisms of the increased mortality risk associated with depression in patients with diabetes remains to be elucidated," the authors write. "It is generally suggested that depression is associated with poor glycemic control, an increased risk of diabetes complications, poor adherence to diabetes management by patients and isolation from the social network." In addition, diabetes and depression are both linked to unhealthy behaviors such as smoking, poor diet and a sedentary lifestyle, and depression could trigger changes in the nervous system that adversely affect the heart.

"Considering the size of the population that could be affected by these two prevalent disorders, further consideration is required to design strategies aimed to provide adequate psychological management and support among those with longstanding chronic conditions, such as diabetes," the authors conclude.

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Journal Reference:

1. A. Pan, M. Lucas, Q. Sun, R. M. van Dam, O. H. Franco, W. C. Willett, J. E. Manson, K. M. Rexrode, A. Ascherio, F. B. Hu. Increased Mortality Risk in Women With Depression and Diabetes Mellitus. Archives of General Psychiatry, 2011; 68 (1): 42 DOI: 10.1001/archgenpsychiatry.2010.176

University of Michigan Health System researchers have found new evidence that our genes help determine our susceptibility to depression.

Their findings, published online in the Archives of General Psychiatry, challenge a 2009 study that called the genetic link into question and add new support to earlier research hailed as a medical breakthrough.

In the summer of 2003, scientists announced they had discovered a connection between a gene that regulates the neurotransmitter serotonin and an individual's ability to rebound from serious emotional trauma, such as childhood physical or sexual abuse.

The journal Science ranked the findings among the top discoveries of the year and the director of the National Institute of Mental Health proclaimed, "It is a very important discovery and a real advance for the field."

That excitement was dampened in 2009, however, after the research was called into question by a study published in the Journal of the American Medical Association. The New York Times reported that analysis, which examined results from 14 different studies, showed the initial findings had "not held up to scientific scrutiny."

Srijan Sen, M.D., Ph.D, an assistant professor of psychiatry at the University of Michigan Medical School, and his colleagues are presenting a new, broader analysis of the follow-up studies to date. The U-M team examined 54 studies dating from 2001 to 2010 and encompassing nearly 41,000 participants — making it the largest analysis of the serotonin gene's relationship to depression.

"When we included all the relevant studies, we found that an individual's genetic make-up does make a difference in how he or she responds to stress," says Sen.

The U-M analysis supports previous findings that individuals who had a short allele on a particular area the serotonin gene had a harder time bouncing back from trauma than those with long alleles.

Rudolf Uher, Ph.D., a clinical lecturer at the Institute of Psychiatry in London, says the U-M research will help cut through the debate about the genetic connection and refocus the field on making new advances to help those affected by mental illness.

"The major strength of the analysis is that it is the first such work that included all studies that were available on the topic," Uher says. "And it gives a very clear answer: the 'short' variant of the serotonin transporter does make people more sensitive to the effects of adversity."

The authors of the initial study from 2003 were also excited by the U-M team's results.

"Their careful and systematic approach reveals why the JAMA meta-analysis got it wrong," says Terrie Moffitt, Ph.D., a professor at Duke University and one of the authors of the 2003 study. "We hope that the same journalists who were so hasty to publish a simplistic claim in 2009 will cover this more thoughtful new analysis."

When the U-M team restricted their analysis to the 14 studies included in the 2009 JAMA paper, they also failed to find a genetic link, suggesting to Sen that the scope of the analysis, not the methodology, was responsible for the new findings.

The U-M analysis found robust support for the link between sensitivity to stress and a short allele in those who had been mistreated as children and in people suffering with specific, severe medical conditions. Only a marginal relationship was found in those who had undergone stressful life events.

But that's also common sense. Different stressful life events may have very different effects, Sen says. For instance, there is no reason to think that the effects of divorce, at a biological level, would be similar to the effects of losing your home or being physically assaulted.

Still, the study results don't mean that everyone should run out and get a genetic test; additional susceptibility from having a short allele is only one factor among many that determine how an individual responds to stress, Sen says.

Additional research will help to map an individual's genetic profile for depression.

"This brings us one step closer to being able to identify individuals who might benefit from early interventions or to tailor treatments to specific individuals," Sen says.

Funding: The research was supported by grants from the National Institutes of Health, University of Michigan Depression Center and Studienstiftung des Deutschen Volkes.

Additional U-M Authors: Margit Burmeister, Ph.D., Kerby Shedden, Ph.D., former graduate student Katja Karg

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Journal Reference:

1. Katja Karg; Margit Burmeister; Kerby Shedden; Srijan Sen. The Serotonin Transporter Promoter Variant (5-HTTLPR), Stress, and Depression Meta-analysis Revisited: Evidence of Genetic Moderation. Archives of General Psychiatry, 2011; DOI: 10.1001/archgenpsychiatry.2010.189

— Many people in the U.S. have multiple common chronic diseases such as diabetes and heart disease, which complicates health care needs. When depression coexists with diabetes, heart disease, or both, health outcomes are often less favorable.

In a randomized controlled trial, testing a primary care intervention called TEAMcare, nurses worked with patients and health teams to manage care for depression and physical disease together, using evidence-based guidelines. The result for patients: less depression, and better control of blood sugar, blood pressure and cholesterol and improved quality of life.

Researchers at the University of Washington (UW) and Group Health Research Institute published their findings in the December 30, 2010 New England Journal of Medicine.

"Depressed patients with multiple uncontrolled chronic diseases are at high risk of heart attack, stroke and other complications," said Dr. Wayne J. Katon, a UW professor of psychiatry and behavioral sciences and an affiliate investigator at Group Health Research Institute. "We are excited about finding a new way to help patients control these chronic diseases, including depression. Then they can get back to enjoying what makes their lives worth living," he said.

Depression is common in patients with diabetes and heart disease, and it has been linked to worse self-management and more complications and deaths. Depression can make people feel helpless and hopeless about managing other chronic diseases. In turn, coping with chronic disease can worsen depression. This tangle of health problems can feel overwhelming — for patients, their families and their health care providers.

To explore possible solutions, the trial focused on 214 Group Health Cooperative patients who were randomly assigned to either standard care or the TEAMcare intervention. In the TEAMcare intervention, a nurse care manager coached each patient, monitored disease control and depression, and worked with the patient's primary care doctors to make changes in medications and lifestyle when treatment goals were not reached. Working together, the nurse and patient set realistic step-by-step goals: reductions in depression and blood sugar, pressure and cholesterol levels. Patients assigned to the standard care arm of the study did not receive the nurses' coaching and monitoring services.

To reach these goals, the nurse regularly monitored the patient's mental and physical health. Based on guidelines that promoted incremental improvements, the care team offered recommendations to the patient's primary care doctor to consider changes to the dose or type of medication used for managing blood pressure, blood sugar, lipids or depression. This process is called "treating to target."

Katon said that the "treating to target" approach helped boost patients' confidence as goals were accomplished. "It reverses what happens when they set overly ambitious goals they don't reach, which discourages them, their families, and health care providers."

At one year — compared with the standard care control group — patients with the TEAMcare intervention were significantly less depressed and also had improved levels of blood glucose, low-density lipoprotein (LDL) cholesterol, and systolic blood pressure. These differences are clinically significant, particularly if achieved in large numbers of patients, Katon said.

"Each of these four disease control measures has been linked to higher risks of complications and deaths from diabetes and heart disease," he added.

The researchers have not yet completed their analysis of possible cost savings from the intervention, but they estimated that the two-year TEAMcare intervention cost $1,224 per patient, on average. This is for patients whose medical care costs health care systems approximately $10,000 per year, said Katon.

TEAMcare intervention patients reported enhanced quality of life and satisfaction with care for depression and either diabetes, heart disease or both. Patients were more likely to have timely adjustment of glucose levels, high blood pressure, cholesterol and antidepressant medications.

"TEAMcare is a truly patient-centered approach that enhances a primary care team to deliver optimal care for both physical and mental health in a seamless manner," said co-author Elizabeth H.B. Lin, MD, MPH, Group Health family physician and an affiliate investigator at Group Health Research Institute. "It recognizes there can be no health without mental health."

This trial is the culmination of more than 25 years of collaboration between the UW and Group Health to improve care for patients with chronic diseases including depression in everyday primary care settings.

Other co-authors were: Paul Ciechanowski, MDCM, MPH, of the UW School of Medicine's Department of Psychiatry and Behavioral Sciences and an affiliate investigator at Group Health Research Institute; Bessie Young, MD, MPH, of the UW School of Medicine's Department of Medicine and Veterans Affairs Puget Sound Health Care; Michael Von Korff, ScD, Evette J. Ludman, PhD, Do Peterson, MS, and Mary McGregor, MSN, of Group Health Research Institute; Carolyn M. Rutter, PhD, of Group Health Research Institute and the Department of Biostatistics of the UW School of Public Health; and David McCulloch, MD, of Group Health.

The National Institute of Mental Health funded the TEAMcare trial, with institutional support from Group Health Cooperative.

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Journal Reference:

1. Wayne J. Katon, Elizabeth H.B. Lin, Michael Von Korff, Paul Ciechanowski, Evette J. Ludman, Bessie Young, Do Peterson, Carolyn M. Rutter, Mary McGregor, David McCulloch. Collaborative Care for Patients with Depression and Chronic Illnesses. New England Journal of Medicine, 2010; 363 (27): 2611 DOI: 10.1056/NEJMoa1003955