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Depression is believed to have a biological basis, caused by low levels of chemical messengers in the brain, especially serotonin and norepinephrine. These natural substances, called neurotransmitters, carry electrical signals from one nerve cell in the brain to another across spaces (called synapses). Although an imbalance in levels of these neurotransmitters may be ultimately responsible for a person's depressed mood, live events such as the death of a loved one, change in marital status, financial problems or job loss also can trigger, maintain or be a consequence of depressive feelings.

Several theories about the causes of depression have been proposed and researched.  Factors which have been studied include: stress (e.g., financial pressures, the build-up of daily "hassles," etc.), loss (e.g., death of someone close to us, loss of identity as a top student in a high school, break-up of a relationship, etc.), low rewards (e.g., few pleasurable events to look forward to), "anger turned inward" (e.g., stuffing away angry feelings and hoping they will go away) rigid or distorted thinking patterns (e.g., the belief that one must be perfect right now or that it is essential that one be loved by everyone), genetic predisposition, physical illness, lack of sunlight during the winter months, and other physiological causes.

Combinations of these factors can make it more likely that a person will become depressed. Some individuals can identify an event that seemed to trigger their depression; other individuals cannot point to a cause of their depression. It is often difficult to distinguish whether severe depression is either "chemical" or "emotional," since depression involves both aspects of functioning: a severely depressed person is likely to feel sad, to experience problems in living, and to exhibit changes in physiological functioning.

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