Office of Research & Development


Depression icon

Depression is an illness that causes those who have it to feel sad, lose interest in activities they've always enjoyed, withdraw from others, and have little energy. Depression can also cause people to feel hopeless about the future, and even to think about suicide.

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.

Depression is a common but serious illness, and most who experience it need treatment to get better. The good news is that depression, even in its most severe forms, is a highly treatable disorder.

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; understanding whether certain 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.

Selected Major Accomplishments

  • VA's TIDES program provides an evidence-based collaborative approach to depression management.
  • VA and UCSF's Heart and Soul study has produced more than 135 papers on how psychological factors influence the outcomes of patients with coronary heart disease.
  • VA researchers have found that serotonin and norepinephrine reuptake inhibitors (SNRIs) may be more effective in treating depression symptoms than drugs that affect only serotonin (SSRIs).

Selected Milestones and Major Events


Major depression is currently the leading cause of disability in the United States, and by 2020 it is projected to be the leading cause of disability worldwide. It's estimated that, fewer than one-fourth of Americans who have an episode of depression during a 12-month period receive appropriate treatment.

Depression is the second most prevalent, chronic, disabling, and costly illness in VA health care settings. It is also prevalent among Veterans with other chronic mental and physical illnesses.

Most VA patients who are found to have depression receive their diagnosis by VA primary care physicians. A 2005 study showed that about 20 percent of primary care patients screen positive for depression symptoms.

In 2008, VA estimated that about one of every three Veterans visiting primary care clinics has some symptoms of depression; one in five has serious symptoms that suggest the need for further evaluation for major depression; and one in eight to ten has major depression, requiring treatment with psychotherapy or antidepressants.

VA Research's response

As part of a comprehensive research agenda aimed at advancing the care of Veterans with depression, VA researchers are developing, testing, and implementing ways to do a better job of screening for and treating the disease.

They are also studying ways to improve outcomes for Veterans affected by depression along with other conditions, such as heart disease or diabetes, and exploring the genetic and molecular roots of the condition with the goal of developing more effective drugs.

VA researchers have found 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 is an evidence-based collaborative approach to depression management that has been successfully incorporated into the VA system. (TIDES is an acronym for "Translating Initiatives for Depression into Effective Solutions.")

VA's Quality Enhancement Research Initiative (QUERI) has been a leader in making knowledge gained by TIDES researchers available to VA mental health practitioners. For example, a QUERI-funded adaptation of TIDES for human immunodeficiency virus (the virus that causes AIDS) led to improved physical and depression outcomes for those with HIV.

Recent accomplishments

A 2008 VA/UCSF study 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.

By examining the health histories of more than 350,000 Veterans over a seven-year period, other VA researchers found those with depression were 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 PTSD also raises the risk—but to a lesser degree. Researchers are continuing to study whether treating these mental disorders reduces heart risk.

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.

Further research is needed to confirm this finding, and to determine whether treating depression in mid-life can help keep away later depression.

VA researchers and their research colleagues have found that duloxetine (sold as Cymbalta), part of a class of drugs called serotonin and norepinephrine reuptake inhibitors, or SNRIs, is more effective in treating depression symptoms than drugs that affect only serotonin, or SSRIs. (Serotonin is a compound present in blood platelets and serum that constricts the blood vessels and transmits messages between the brain's billions of nerve cells.)

Results of the study showed that duloxetine provided greater improvements in pain and functioning than four generic SSRI drugs used in the research.

Ongoing studies

An ongoing four-year study is examining whether talk therapy through in-home videoconferencing can help to treat older Veterans who have major depression. The study includes 224 Veterans living in and around Charleston, S.C. After eight weeks of treatment, patients were followed for 12 months.

Preliminary results of the project indicate that mental health therapy for elderly people with major depression can be delivered just as effectively by in-home video teleconference as by face-to-face-therapy sessions, and that the results of the therapy are sustained after a year. The team is now looking at whether providing therapy in this way is cost effective.

The Heart and Soul study is an ongoing project conducted by VA and UCSF researchers and their colleagues. It was designed 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. They have been followed ever since to understand the association between psychological factors and cardiovascular events.

More than 135 papers have already been published using data from the study, and still more are expected.

More on our Website

VA Research Fact Sheet: Depression

Study confirms that depression can shorten life, VA Research news feature

Prolonged exposure therapy yields results for PTSD, depression, VA Research Currents (online only) September 13, 2013

'Loving-kindness' meditation shows promise in pilot study, VA Research Currents, Fall 2013

Study underscores body-mind connection, VA Research Currents, September-October 2012

Collaborative Care for Depression in the Primary Care Setting : a primer on VA's Translating Initiatives for Depression into Effective Solution's (TIDES) project

Determining key features of effective depression interventions, VA Health Services Research & Development.

Serious Mental Illness Treatment Resource and Evaluation Center (SMITREC).

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, anxiety disorder unspecified, panic disorder and PTSD were at increased risk of heart attack. Am Heart J. 2010 May;159(5):772-9.

A pragmatic 12-week, randomized trial of duloxetine versus generic selective serotonin-reuptake inhibitors in the treatment of adult outpatients in a moderate-to-severe depressive episode . Martinez JM, Katon W, Greist JH, Kroenke K, Thase ME, Meyers AL, Edwards SE, Marangell LB, Shoemaker S, Swindle R. Significantly greater benefit for duloxetine compared with SSRIs was demonstrated on measures of pain and functioning. Int Clin Psychopharmacol. 2012 Jan;27(1);17-26.

Diagnosis and treatment of depression in adults with comorbid medical conditions: a 52-year-old man with depression . Whooley MA. Using the case of Mr. J, a 52-year-old man with depressive symptoms and several comorbid medical conditions, diagnosis and treatment of depression are discussed. JAMA 2012 May 2;307(17):1848-57.

Midlife vs. late-life depressive symptoms and risk of dementia: differential effects for Alzheimer's disease and vascular dementia . Barnes DE, Yaffe K, Byers AL, McCormick M, Schaefer C, Whitmer RA. Depressive symptoms in midlife or late life are associated with an increased risk of developing dementia. Arch Gen Psychiatry, 2012 May;69(5);493-8.

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

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

Mental Illness Research, Education, and Clinical Centers (MIRECC), 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

Defense Suicide Prevention Office , U.S. Department of Defense

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