Biological Factors
The underlying causes of depression are not well understood, although there are a lot of clues suggesting that various systems in the brain may cause depression or be affected by it. For example, major depression is characterized by excessive sleep. So, it is very likely that the brain stem (which controls sleep) plays a role in depression. Similarly, abnormalities in the cerebral cortex (which controls thinking) probably have to do with the inability to concentrate and negative thoughts that can be characteristic of depression.
Imbalances in neurotransmitters (chemicals in the nervous system) seem to play a key role in depression. Research into the way antidepressant medication function has provided the greatest insight in this area. For example, certain medications used to treat depression have been shown to increase the amount of neurotransmitters such as norepinephrine, serotonin and dopamine in the brain; this suggests that a chemical imbalance in the brain causes depressive symptoms. Abnormalities in the neuroendocrine system of the brain also seem to play a role in depression, including abnormalities linked to the thyroid, pituitary and adrenal glands.

Genetic Factors
Individuals with a family history of depression have a greater risk of becoming depressed than the general population. Some researchers believe that a "single depression gene" exists, but there is mounting evidence to suggest that several genes may be responsible for causing depression.

Social and Environmental Factors
Social and environmental factors also may cause depression, but there are many conflicting studies concerning this issue. For example, some studies suggest that adverse life events such as divorce, serious illness or multiple episodes of misfortune may cause depression. Other studies have found that no such relationship exists.

Strokes and Depression
In some cases, a stroke may cause depression. Strokes that cause depression are more likely to occur in the left frontal lobe of the brain, but they can be found elsewhere. One study of older adults found that damage to specific areas of the brain (subcortical white matter lesions) were more likely to be found in people with major depression than in healthy individuals, or patients with dementia (progressive decline in the ability to think and reason). These small, subcortical strokes are the type found in individuals with long-standing high blood pressure (hypertension), diabetes or other medical illnesses that affect blood vessels in the brain, heart and other organs.