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What Causes Depression?


Updated September 26, 2013

Written or reviewed by a board-certified physician. See About.com's Medical Review Board.

The causes of depression are not completely understood at this time, but it is believed that it is most likely a combination of biology, genetics, and environment that makes certain people more prone to developing this condition.

Biological Factors

In order to understand the biological roots of depression, it is first important to understand a little bit about how the brain works. The brain is composed of millions of nerve cells called neurons. These neurons are in close proximity to each other. When communication between neurons needs to occur, chemical messengers called neurotransmitters are released, which then cross the gap between communicating neurons and bind to receptor sites on the receiving neuron.

When all is functioning normally, the message gets passed along from neuron to neuron in this manner until it reaches its target. In people with depression, however, there is thought to be a problem with this process, causing a breakdown in neural communication.

Three particular neurotransmitters have been widely studied in relation to depression: serotonin, norepinephrine, and dopamine. It is believed that imbalances in these substances are important in the development of depression, although others, such as gamma-Aminobutyric acid (GABA), may play a role as well.

Female sex hormones are also believed to play a role in depression causation, perhaps by influencing neurotransmitters. It has been widely documented that about twice as many women as men suffer from depression, with the incidence of depression among women correlating with times when hormones are in flux, such as menstruation, childbirth, and perimenopause. Furthermore, a woman's risk for depression lessens after menopause.

Additionally, the stress hormone cortisol has been implicated in depression. Although the relationship between cortisol and depression is complex, some research has shown that elevated cortisol, as can occur with chronic stress, may impact serotonin functioning and contribute to depression.

Genetic Factors

Although no studies thus far have been able to pinpoint what specific gene or combination of genes might be involved in depression, the evidence does point to a link between genetic inheritance and depression vulnerability.

People who have a parent, brother, sister, or child with major depression have been found to be anywhere from two to four times more likely to have major depression than other people.

In addition, studies comparing pairs of twins provide compelling evidence. In one study, if a non-identical twin (similar, but not identical, genetic material) was found to have had depression, there was a 20 percent chance that the other twin would develop depression. However, if an identical twin (identical genetic material) had depression, the other twin had about a 50 percent likelihood of developing depression.

As further evidence of depression's genetic link, certain inherited personality traits, such as neuroticism, appear to to be risk factors for major depression. Individuals with this type of personality tend to be more likely to respond to stressful situations in a negative way and to interpret these situations as threatening or hopeless.

Environmental Factors

Environmental stress, both past and present, has been linked to depression risk. People who experience adverse circumstances during their youth -- such as physical and sexual abuse, poor relationships with their parents, and divorce -- are more likely to develop major depression later in life. In theory, childhood adversity may predispose individuals to future depression by making their brains more sensitive to stress. Current environmental stressors -- such as job loss, marital strife, health problems, and loss -- are also associated with a greater risk for depression, presumably because chronically high levels of the stress hormone cortisol may influence serotonin levels.


Espejo, E.P. et. al. "Stress sensitization and adolescent depressive severity as a function of childhood adversity: a link to anxiety disorders." Journal of Abnormal Child Psychology. 23.2 (2007): 287-99.

Heina, A., et. al. "Relationship between cortisol and serotonin metabolites and transporters in alcoholism (correction of alcolholism)." Pharmacopsychiatry 35.4 (2002):127-34.

Katz, Vern L. et. al., eds. Comprehensive Gynecology. 5th ed. Philadelphia: Mosby, 2007.

Moore, David P. and James W. Jefferson. Handbook of Medical Psychiatry. 2nd Ed. Philadelphia: Mosby, Inc., 2004.

Stern, Theodore A. et. al. eds. Massachusetts General Hospital Comprehensive Clinical Psychiatry. 1st ed. Philadelphia: Mosby Elsevier, 2008.

Tafet, G.E., et. al. "Correlation between cortisol level and serotonin uptake in patients with chronic stress and depression." Cognitive, Affective, & Behavioral Neuroscience 1.4 (2001) :388-393(6).

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