Office of Research & Development

VA research on

Depression


Introduction

Depression causes sadness, loss of interest in activities people once enjoyed, withdrawal from others, and have little energy. Depression can also cause people to feel hopeless about the future and even think about suicide.

According to the National Institute of Mental Health (NIMH), major depression is one of the most common mental disorders in the United States, and it carries the heaviest burden of disability among mental and behavioral disorders. In 2014, NIMH estimated that some 15.7 million adults aged 18 or older in the United States had at least one major depressive episode in the past year. This number represented 6.7 percent of all U.S. adults.

Most experts believe a combination of genes and stressful life events can cause depression. Health problems such as anemia or an underactive thyroid gland can also lead to depression, as can certain medicines, such as steroids or narcotics.

Most people who experience depression need treatment to get better. The good news is that depression, even in its most severe forms, is a highly treatable disorder.

In 2008, VA estimated that about 1 in 3 Veterans visiting primary care clinics has some symptoms of depression; 1 in 5 has serious symptoms that suggest the need for further evaluation for major depression; and 1 in 8 to 10 has major depression, requiring treatment with psychotherapy or antidepressants.

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Selected Major Accomplishments

  • 2006: Developed, through VA's TIDES project, an evidence-based collaborative approach to depression management
  • 2006: Began the Heart and Soul Study, on how psychological factors influence the outcomes of patients with coronary heart disease
  • 2008: Demonstrated that the link between depression and heart disease may hinge largely on behavioral factors associated with depression, such as lack of exercise and increased smoking
  • 2012: Found that serotonin and norepinephrine reuptake inhibitors (SNRIs) may be more effective in treating depression symptoms than drugs that affect only serotonin (SSRIs)
  • 2015: Learned that talk therapy delivered by two-way video calls is at least as effective as in-person treatment delivery for older Veterans with depression

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New, Ongoing, and Published Research

VA researchers are making important headway in treating, screening, and diagnosing depression and other mood disorders such as bipolar disorder, persistent despondency, and seasonal affective disorder.

Researchers are developing models of family interventions and social support to help Veterans recover from mood disorders, learning which risk factors make a person more likely to suffer from depression or to respond positively to a specific medication, and identifying and testing potential new drugs for depression and other disorders.

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➤ Depression among Veterans and non-Veterans

A team from the VA Palo Alto Health Care System and Stanford University School of Medicine examined data on 7,000 men age 50 or older in a study published in 2014, and found that Veterans were no more likely than non-Veterans to have depression or anxiety.

Because Veterans, especially those who served in combat, have generally experienced more stress and trauma in their lives than non-Veterans, the team had expected to see higher rates of depression among Veterans. Instead, they found just the opposite. Older Veterans actually scored better than non-Veterans in the same age group.

The team found 11 percent of Veterans reported elevated rates of depression, compared with 12.8 percent of non-Veterans. For anxiety, 9.9 percent of Veterans reported elevated levels, versus 12.3 percent for non-Veterans. These differences were not considered statistically significant.

Vietnam Veterans, however, were twice as likely to have elevated depression and anxiety than World War II or Korean War Veterans in the study. The team suggested further studies are needed to determine why this was true.

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➤ The TIDES project

VA researchers have learned that a team approach to providing care can improve the management of mental health conditions, as it has also been shown to do for other illnesses. VA's TIDES project demonstrated the value of an evidence-based collaborative approach to depression management that has now been successfully incorporated into the VA system. (TIDES is an acronym for "Translating Initiatives for Depression into Effective Solutions.")

The TIDES project provided guidelines for collaboration between mental health and primary care specialists with support for assessment and triage, patient education, and proactive follow-up of patients with symptoms of depression. The guidelines have helped VA systematically integrate collaborative care for depression into primary care settings throughout the VA health care system.

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➤ The VAST-D study

Several types of depression medications, or antidepressants, are used to treat depression and conditions in which depression is a component of the disease (such as bipolar disorder). These drugs improve symptoms of depression by increasing the availability of brain chemicals called neurotransmitters. It is believed that these chemicals help regulate brain circuits that affect emotions.

Often, the first antipsychotic medication physicians choose for their patients does not work well. The VA Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D) study, a VA cooperative study (CSP No. 576), is now underway at 34 VA facilities throughout the nation. Study researchers are working to determine research-based next steps for outpatients with major depressive disorder who have not had satisfactory outcomes to standard first-step treatments.

The team will attempt to determine for which patients, and under what circumstances, it is better to switch to other antidepressants, versus augmenting the first medication that was prescribed.

Researchers will also look at the results of augmenting the first medication with atypical antipsychotics, a newer generation of drugs used to help treat depression. These results will be compared with those achieved by switching to or augmenting the first medication with more "typical" medications first developed in the 1950s. These "first generation" antipsychotics include Haldol and Thorazine.

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➤ Non-drug treatments for depression

Telemedicine talk therapy—In 2015, a study led by researchers from VA's Heath Equity and Rural Outreach Innovation Center (HEROIC) in Charleston, S.C., found that talk therapy delivered by two-way video calls is at least as effective as in-person treatment delivery for older Veterans with depression.

In the study, the research team recruited 241 Veterans aged 58 or older with major depression. The Veterans were randomly assigned to receive either telemedicine or same-room psychotherapy. both groups received the same kind of treatment: behavioral activation, a talk therapy that emphasizes reinforcing positive behaviors.

The team found that telemedicine-delivered psychotherapy produced similar outcomes to in-person treatment. After a year of treatment, 39 percent of telemedicine patients and 46 percent of in-person therapy patients were no longer depressed, according to structured clinical interviews.

The team concluded that telemedicine is a good option for depressed older adults who have barriers to mobility, have some kind of stigma, or are geographically isolated.

Transcranial magnetic stimulation—Researchers at eight VA medical centers throughout the nation are conducting a cooperative study (CSP No. 556) to determine if repetitive transcranial magnetic stimulation (TMS) helps Veterans with depression and possible PTSD or substance abuse who have not responded adequately to medication. The therapy is already approved by the Food and Drug Administration to treat refractory (treatment-resistant) depression, but past studies have typically not included patients who also have other mental conditions—such as PTSD or substance abuse—along with their depression. Such combinations are more common in VA patients than in the general population.

In TMS, clinicians take an electromagnetic coil, charge it with electricity, and apply it to specific points on the skull. The result is a targeted magnetic field that can affect brain cells in a specific area.

Participants in the study receive a 30-minute session of this kind, five days per week, for six weeks. Researchers use the electronic coil to stimulate the participants' prefrontal cortex, the part of the brain responsible for emotions and mood regulation.

The study is expected to be completed in spring 2016.

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➤ Depression and heart disease: the Heart and Soul Study

The Heart and Soul Study is an ongoing project led by VA and University of California, San Francisco, researchers. It is helping to determine how psychological factors influence the outcomes of patients with coronary heart disease.

A total of 1,024 patients in the San Francisco area, including 440 Veterans, were enrolled in the study between 2000 and 2002. Researchers have followed them ever since to understand the association between psychological factors and cardiovascular events.

A 2008 paper by study researchers, published in the Journal of the American Medical Association, provided evidence that the link between depression and heart disease may hinge largely on behavioral factors associated with depression, such as lack of exercise and increased rates of smoking.

The most recent study by the Heart and Soul team, published in 2016, further explored whether depression is mainly a cause or a consequence of poor health behaviors.

The team found that among 667 patients with coronary heart disease, depressive symptoms were linked to a range of lifestyle risk factors. These risk factors included smoking, low levels of physical activity, poor sleep quality, and poor medical adherence. The research showed that each of these lifestyle factors significantly worsened over a five-year period in depressed individuals, more so than in individuals who were not depressed. This lends credence to the idea that depression is primarily a cause of poor health behaviors, rather than a consequence. Researchers continue to study this question, with the goal of generating additional insights to help guide prevention and treatment.

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➤ Depression and heart disease: other VA studies

Mental disorders and heart attack risk—By examining the health histories of more than 350,000 Veterans over a seven-year period, researchers from the St. Louis VA Medical Center reported, in 2010, that those with depression are at about 40 percent higher risk than others for having a heart attack.

General anxiety and panic disorder seem to raise the risk to a similar extent, and posttraumatic stress disorder (PTSD) also raises the risk—but to a lesser degree. Researchers are continuing to study whether treating these mental disorders reduces heart risk.

Vascular depression—In a follow-up study, whose results were published in 2012, researchers found that those who had depression in middle age were at an increased risk of developing vascular depression (depression caused by reduced or blocked blood flow to the brain) in old age, and that their mid-life depression could be a causal risk factor.

Ischemic heart disease—In 2014, researchers at the VA Puget Sound Health Care System reported that Veterans with depression are more likely to complain of increased chest pain related to ischemic heart disease.

Ischemia is a condition in which blood flow, and therefore oxygen, is restricted or reduced in a part of the body. Ischemic heart disease, also known as coronary artery disease, is the term given to heart problems caused by narrowed heart arteries.

The research team's findings indicated that changes in depression symptoms could affect the perception of a patient's chest pain, or angina. The greater the perception of chest pain, regardless of the actual extent of the disease, the greater the likelihood of cardiac intervention. Multiple procedures and tests are both costly and can adversely affect quality of life.

In their study of 569 Veterans, the team found that Veterans whose depression had begun recently were the ones most dramatically affected, reporting more chest pain and physical limitations, along with poorer quality of life. Veterans who were persistently depressed also reported more problems in these areas than those with ischemic heart disease who were not depressed.

CART-CL—Through the CART-CL (Clinical Assessment Reporting and Tracking System for Cath Labs) program, VA researchers are focusing in on how cardiac catheterization is done at VA laboratories throughout the nation. The CART-CL program collects data from all 77 VA cath labs. Researchers use that data to improve VA's clinical performance.

Cardiac catheterization is used to diagnose and treat cardiovascular conditions. During the procedure, a long thin tube called a catheter is inserted in an artery or vein in the groin, neck, or arm, and is threaded through the blood vessels to the heart. The procedure allows cardiologists to investigate what's going on in the heart, or to open blocked arteries impeding blood flow.

A 2015 study by researchers with the VA Ann Arbor Healthcare system and the University of Michigan used CART-CL data to look at nearly 86,000 Veterans who underwent the procedure at a VA facility between October 2007 and September 2012. Nearly 3,200 of those Veterans were women.

The researchers found that women Veterans who underwent the procedure tended to be younger and more obese than men, and that they were more likely to have PTSD or depression. They were also significantly less likely to have obstructive coronary disease, and consequently were less likely to have been prescribed heart medications.

However, their long-term health outcomes were about the same as those of their male counterparts. According to the research team, the findings suggest that a significant percentage of women Veterans may have chest pain that is not attributable to obstructive coronary artery disease, and that further research is needed into the reasons for that chest pain.

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➤ Iraq and Afghanistan Veterans and depression

Many Iraq and Afghanistan Veterans have developed mental and behavioral conditions as a result of their combat experiences or other war-zone stressors. A 2015 study by researchers at VA's Translational Research Center for TBI and Stress Disorders at the VA Boston Healthcare System identified three such conditions that cause the greatest level of difficulty in Veterans when they occur together.

The three conditions are depression, PTSD, and traumatic brain injury (TBI). Patients with those conditions, which the researchers call the "deployment trauma factor," have higher disability scores than those with any other three-diagnosis combination.

The disabilities measured include difficulty in getting around, communicating and getting along with others, self-care, and other daily tasks. Other common problems that appeared to predict disability included anxiety conditions other than PTSD, pain along with sleep difficulty, and substance abuse or dependence.

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➤ Seasonal affective disorder

In a 2015 study, researchers from VA's Baltimore and Denver Mental Illness Research Education and Clinical Centers (MIRECCs), along with researchers from several universities, found that cognitive behavioral therapy (CBT) can help Veterans and others with seasonal affective disorder (SAD). CBT is a form of psychotherapy that focuses on the integral relationship between people's thoughts and their behaviors.

SAD is a form of clinical depression that occurs in fall and winter and is more highly prevalent in those who live in northern climates. The current prevalent treatment for SAD is light therapy, in which a patient sits in front of a bright light unit every day for a designated period of time to help regulate his or her body clock. Patients also receive antidepressants, mood stabilizing medications, or psychotherapy if needed.

In this study, some patients received CBT twice per week over six weeks in group sessions with a community therapist. They focused on behaviors that would help them cope with winter, such as changing negative thoughts associated with winter, and were encouraged to engage in fun activities during the winter to counteract their avoidance mechanisms. Others received light therapy instead.

The research team concluded that, while results from the two groups were similar, CBT may be better overall for patients with SAD. This is because CBT develops skills patients can use once the treatment ends, whereas light therapy requires daily therapy—every winter.

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➤ Genomics

The Office of Research and Development will soon be funding a project led by the Genomic Medicine Implementation, HSR&D, and QUERI programs to study the genomics of major depressive disorder in Veterans. The project will examine strategies to use patients' genetic information to prescribe the best antidepressants and discover the most effective dosage.

Until now, there have not been many studies of genomic testing implementation in the clinical care setting. This program will actually return genomic test results to providers and patients, which may subsequently influence treatment. The study will look at at the most effective way return results to clinicians and patients to directly guide treatment. This type of study could serve as a primer for similar studies going forward.

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More on Our Website

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Selected Scientific Articles by Our Researchers

Developing effective collaboration between primary care and mental health providers. Felker BL, Chaney E, Rubenstein LV, Bonner LM, Yano EM, Parker LE, Worley LLM, Sherman SE, Ober S. Programs like TIDES that have implemented collaboration between primary care and mental health services have resulted in improved patient care. Prim Care Companion J Clin Psychiatry, 2006; 8(1):12-16

Depressive symptoms, health behaviors, and risk of cardiovascular events in patients with coronary heart disease. Whooley MA, de Jonge P, Vittinghoff E, Otte C, Moos R, Carney RM, Ali S, Dowray S, Na B, Feldman MD, Schiller NB, Browner WS. In this sample of outpatients with coronary heart disease, the association between depressive symptoms and adverse cardiovascular events was largely explained by behavioral factors, particularly physical inactivity. JAMA, 2008 Nov 26;300(20):2379-88.

Anxiety disorders increase risk for incident myocardial infarction in depressed and nondepressed Veterans Administration patients. Scherrer JF, Chrusclel T, Zeringue A, Garfield LD, Hauptman PJ, Lustman PJ, Freedland KE, Carney RM, Bucholz KK, Owen R, True WR. In VA patients free of heart disease in 1999 and 2000, those with depression, unspecified anxiety disorders, panic disorder and PTSD were at increased risk of heart attack. Am Heart J, 2010 May;159(5):772-9.

Depression and anxiety symptoms in male Veterans and non-Veterans: the Health and Retirement Study. Gould CE, Rideaux T, Spira AP, Beaudreau SA. In a community-based sample of men aged 50 and older, Veteran status was not associated with the presence of elevated depression and anxiety symptoms. Int J Geriatr Psychiatry, 2015 Jun;30(6):623-30.

Angina symptom burden associated with depression status among Veterans with ischemic heart disease. Trivedi R, Gerrity M, Rumsfeld JS, Spertus JA, Sun H, McDonell M, Doak M, Lucas L, Fihn SD. Depression and angina outcomes are significantly associated. Ann Behav Med, 2015 Feb;49(1):58-65.

Characteristics and outcomes of women Veterans undergoing cardiac catheterization in the Veterans Affairs healthcare system: insights from the VA CART program. Davis MB, Maddox TM, Langner P, Plomondon ME, Rumsfeld JS, Duvernoy CS. Women Veterans undergoing catheterizations are younger, have more obesity, depression, and PTSD, less obstructive coronary artery disease, and similar long-term outcomes, compared with men. Circ Cardiovasc Qual Outcomes, 2015 Mar;8(2 Suppl 1):S39-47.

Deployment-related psychiatric and behavioral conditions and their association with functional disability in OEF/OIF/OND Veterans. Lippa SM, Fonda JR, Fortier CB, Amick MA, Kenna A, Milberg WP, McGlinchey RE. Depression, PTSD, and a history of military mild TBI may comprise an especially harmful combination associated with high risk for substantial disability. J Trauma Stress, 2015 Feb 28(1):25-33.

Identification of a common neurobiological substrate for mental illness. Goodkind M, Eickhoff SB, Oathes DJ, Jiang Y, Chang A, Jones-Hagata LB, Ortega BN, Zaiko YV, Roach EL, Korgaonkar MS, Grieve SM, Galatzer-Levy I, Fox PT, Etkin A. A meta analysis of 193 peer-reviewed papers identified a common pattern of loss of gray matter in three brain structures across a spectrum of psychiatric disorders that are widely perceived to be distinct. JAMA Psychiatry, 2015 Apr:72(4):305-15.

Relationship between toxoplasma gondii and mood disturbance in women Veterans. Dufy AR, Beckie TM, Brenner LA, Beckstead JW, Seyfang A, Postolache TT, Groer MW. This study is the first to describe relationships between chronic T. gondii infection, depression, and dysphoric moods in a Veteran population. Mil Med, 2015 Jun;180(6):621-5.

Psychotherapy for depression in older Veterans via telemedicine: a randomised, open-label, non-inferiority trial. Egede LE, Acierno R, Knapp RG, Lejuez C, Hernandez-Tejada M, Payne EH, Frueh BC. Telemedicine-delivered psychotherapy for older adults with major depression is not inferior to same-room treatment. Lancet Psychiatry, 2015 Aug;2(8):693-701.

Randomized trial of cognitive-behavioral therapy versus light therapy for seasonal affective disorder: acute outcomes. Rohan KJ, Mahon JN, Evans M, Ho SY, Meyerhoff J, Postolache TT, Vacek PM. Cognitive behavioral therapy for seasonal affective disorder and light therapy are comparably effective for seasonal affective disorder, and both may be considered as treatment options. Am J Psychiatry, 2015 Sep 1;172(9):862-9.

The VA augmentation and switching treatments for improving depression outcomes (VAST-D) study: Rationale and design considerations. Mohamed S, Johnson GR, Vertrees JE, Guarino PD, Weingart K, Young IT, Yoon J, Gleason TC, Kirkwood KA, Kilbourne AM, Gerrity M, Marder S, Biswas K, Hicks P, Davis LL, Chen P, Kelada A, Huang GD, Lawrence DD, LeGwin M, Zisook S. Design of a trial of three "next-step" strategies for Veterans who do not achieve remission with their first antidepressant: switching to another antidepressant (bupropion-SR) or augmenting the current antidepressant with either another antidepressant (bupropion-SR) or with an atypical antipsychotic (aripiprazole). Psychiatry Res, 2015 Oct 30:229(3):760-70.

Direction of association between depressive symptoms and lifestyle behaviors in patients with coronary heart disease: the Heart and Soul Study. Sin NL, Kumar AD, Gehi AK, Whooley MA. Among patients with coronary heart disease, depressive symptoms were linked to a range of lifestyle risk factors and predicted further declines in physical activity, medication adherence, and sleep quality. Ann Behav Med, 2016 Jan 27. (Epub ahead of print)

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Depression Fact Sheet

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VA and other U.S. Government Online Resources

Mental Health: Depression, U.S. Department of Veterans Affairs

Mental Health: Bipolar, U.S. Department of Veterans Affairs

Mental Health: Suicide Prevention, U.S. Department of Veterans Affairs

Homeless Veterans Mental Health Services , U.S. Department of Veterans Affairs

Vet Center Program, U.S. Department of Veterans Affairs

Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury , U.S. Department of Defense

Moving Forward: overcoming life's challenges, U.S. Department of Defense

Depression, healthfinder.gov

Depression, Medline Plus

Depression, National Institute of Mental Health, National Institutes of Health

Depression, NIH Senior Health, National Institutes of Health

Get help for depression, U.S. Department of Health and Human Services


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