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The cause of major depression cannot be narrowed down to a single factor. However, it appears that brain chemistry plays a major role. Brain chemicals called neurotransmitters convey messages between the nerves. Too many or too few neurotransmitters, particularly norepinephrine, serotonin and dopamine, are believed to cause alterations in mood.

There are many risk factors for major depression. For instance, women are nearly twice as likely to be diagnosed with major depression as men. Many mental health professionals believe that hormonal changes during pregnancy, miscarriage, menstruation, the postpartum period, peri-menopause and menopause may lead to a major depressive episode.

Individuals with a personal or family history of depression are also at greater risk of developing the condition. Heredity may influence women's risk of developing the disorder more so than men, according to a recent study on twins. People who have had one episode of major depression have a 60 percent chance of having another episode. The risk of major depression may be as high as 25 percent in first-degree relatives (e.g., parents, children, siblings) of patients with a history of major depression, according to the National Alliance on Mental Illness (NAMI).

Other risk factors for major depression include:

• Stressful events or life situations. Individuals who have experienced major stresses, such as the death or prolonged absence of a loved one, divorce, discrimination, abuse or trauma, have an increased risk of major depression. Unrealistic or unreachable expectations or life goals or major obstacles (real or perceived) to life goals and expectations may also increase the risk of major depression.
  
  
• Chronic physical medical conditions. The rate of major depression among patients hospitalized for general medical illnesses is between 10 and 14 percent, according to the National Mental Health Association (NMHA). The more severe the condition, the greater the risk of major depression. Relatives, especially children, of chronically ill or hospitalized patients may also be at an increased risk for major depression. Medical conditions of particular concern include:
  
  
• • Heart disease. About 18 to 20 percent of patients with coronary disease who have not had a heart attack may have a diagnosis of major depression, and as many as 40 to 65 percent of heart attack survivors may have major depression, according to the NMHA. Heart failure is also a risk factor for depression. Depression that is untreated increases the risk of a heart attack.
    
    
  • Stroke. The NMHA reports that as many as 10 to 27 percent of stroke survivors may experience major depression for about a year. Patients who have had a stroke and have an untreated diagnosable major depression have a higher death rate in the six months post stroke than those who either do not have depression or have their depression treated.
    
    
  • Diabetes. The risk of major depression in patients with adult-onset diabetes is as high as 25 percent, according to the NMHA. In addition, as many as 70 percent of patients with diabetic complications, such as kidney failure, may be have a major depressive illness. Untreated major depression is associated with less-effective diabetic control and more side effects of diabetes.
    
    
  • Cancer. An estimated one in four people with cancer have a diagnosable major depression, according to the NMHA. Treating the depression can make a significant difference in their response to cancer treatment and their quality of life. It is not acceptable for a physician to take the position that "I would be depressed too" and fail to treat this illness.
    
    
  • Nutritional deficiency. Several studies report that there may be a link between insufficient vitamin B12 and major depression. Further, replacement of vitamin B12 may increase the probability of recovery from depression. New research also suggests that a low level of vitamin D may increase the risk of depression.
    

Other conditions including obesity, chronic kidney failure, lung disease, fibromyalgia and chronic fatigue syndrome are associated with diagnosable major depressive illness.

In addition, conditions such as hypothyroidism (low levels of thyroid hormone) and anemia (deficiency of red blood cells) may mimic the symptoms of depression and can be misdiagnosed as major depression.

• Medication use. Numerous medications can produce side effects that include symptoms of depression.
  
  
• Other mental health conditions. People with other mental health conditions, such as some eating disorders and some anxiety disorders, are more likely to experience major depression.
  
  
• Substance abuse. People who abuse alcohol, drugs or other substances have an increased risk of major depression. The likelihood of suffering major depression also seems to be increased among cigarette smokers, especially those who smoke heavily. Many treatment providers for substance abuse problems still take the position that treating depression before a period of sobriety is not indicated; however, research supports early treatment when a major depression is diagnosed.
  
  
• Marital status, quality of marriage and lack of social supports. In general, married people have a lower risk of major depression. However, unhappily married people have a much higher risk of the disorder. Individuals who feel rejected or depreciated by a loved one, or who have few or no friends, are also at an increased risk for major depression.
  
  
• Negative patterns of thinking. Individuals who tend to think negatively are at an increased risk of major depression.