The Invisible Disease - Depression

Depression is a serious medical illness. In contrast to the normal emotional experiences of sadness, loss, or passing mood states, clinical depression is persistent and can interfere significantly with an individual's ability to function.

Symptoms of depression include sad mood, loss of interest or pleasure in activities that were once enjoyed, change in appetite or weight, difficulty sleeping or oversleeping, physical slowing or agitation, energy loss, feelings of worthlessness or inappropriate guilt, difficulty thinking or concentrating, and recurrent thoughts of death or suicide. A diagnosis of unipolar major depression (or major depressive disorder) is made if a person has five or more of these symptoms and impairment in usual functioning nearly every day during the same two-week period. Major depression often begins between ages 15-30 or even earlier. Episodes typically recur.

Some people have a chronic but less severe form of depression, called dysthymia (or dysthymic disorder), that is diagnosed when depressed mood persists for at least two years and is accompanied by at least two other symptoms of depression. Many people with dysthymia also have major depressive episodes. While unipolar major depression and dysthymia are the primary forms of depression, a variety of other subtypes exist.

Depression can be devastating to all areas of a person's everyday life, including family relationships, friendships, and the ability to work or go to school. Many people still believe that the emotional symptoms caused by depression are "not real," and that a person should be able to shake off the symptoms if only he or she were trying hard enough. Because of these inaccurate beliefs, people with depression either may not recognize that they have a treatable disorder or may be discouraged from seeking or staying on treatment because of feelings of shame and stigma. Too often, untreated or inadequately treated depression leads to suicide.

  • Depression affects nearly 10 percent of adult Americans ages 18 and over in a given year, or more than 19 million people in 1998.
  • Unipolar major depression is the leading cause of disability in the United States and worldwide.
  • Nearly twice as many women (12 percent) as men (7 percent) are affected by a depressive illness each year.
  • Evidence from studies of twins supports the existence of a genetic component to risk of depression. Across six studies, the average concordance rate in identical twins (40%) for unipolar depression is more than twice the concordance rate in fraternal twins (17%).
  • Research has shown that stress in the form of loss, especially death of close family members or friends, may trigger major depression in vulnerable individuals.


Antidepressant medications are widely used, effective treatments for depression. Existing antidepressant drugs are known to influence the functioning of certain neurotransmitters (chemicals used by brain cells to communicate), primarily serotonin, norepinephrine, and dopamine, known as monoamines. Older medications - tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) - affect the activity of both of these neurotransmitters simultaneously. Their disadvantage is that they can be difficult to tolerate due to side effects or, in the case of MAOIs, dietary and medication restrictions. Newer medications, such as the selective serotonin reuptake inhibitors (SSRIs), have fewer side effects than the older drugs, making it easier for patients to adhere to treatment. Both generations of medications are effective in relieving depression, although some people will respond to one type of drug, but not another. Medications that take entirely different approaches to treating depression are now in development.

Electroconvulsive therapy (ECT), although not generally used as a first-line treatment, is one of the effective treatments for severe depression.

Psychotherapy is also effective for treating depression. Certain types of psychotherapy, cognitive-behavioral therapy (CBT) and interpersonal therapy (IPT), have been shown to be particularly useful. More than 80 percent of people with depression improve when they receive appropriate treatment with medication, psychotherapy, or the combination.

Recently there has been enormous interest in herbal remedies for various medical conditions including depression. One herbal supplement, hypericum or St. John's Wort, has been promoted as having antidepressant properties. However, no carefully designed studies have determined the antidepressant efficacy of the supplement. NIMH is currently enrolling patients in the first large-scale, multi-site, controlled study of St. John's wort as a potential treatment for depression.

Recent Research Findings

Modern brain imaging technologies are revealing that in depression, neural circuits responsible for moods, thinking, sleep, appetite, and behavior fail to function properly, and that the regulation of critical neurotransmitters is impaired. Genetics research indicates that vulnerability to depression results from the influence of multiple genes acting together with environmental factors. Studies of brain chemistry, mechanisms of action of antidepressant medications, and the cognitive distortions and disturbed interpersonal relationships commonly associated with depression, continue to inform the development of new and better treatments. The hormonal system that regulates the body's response to stress - the hypothalamic-pituitary-adrenal (HPA) axis - is overactive in many patients with depression. The hypothalamus, the brain region responsible for managing hormone release from glands throughout the body, increases production of a substance called corticotropin releasing factor (CRF) when a threat to physical or psychological well-being is detected. Elevated levels and effects of CRF lead to increased hormone secretion by the pituitary and adrenal glands which prepares the body for defensive action. The body's responses include reduced appetite, decreased sex drive, and heightened alertness. Research suggests that persistent overactivation of this hormonal system may lay the groundwork for depression. The elevated CRF levels detectable in depressed patients are reduced by treatment with antidepressant drugs, and this reduction corresponds to improvement in depressive symptoms.

Source: National Institute of Mental Health, National Institutes of Health