Depression may be described as feeling sad, blue, unhappy, miserable, or down in the dumps. Most of us feel this way at one time or another for short periods. True clinical depression is a mood disorder in which feelings of sadness, loss, anger, or frustration interfere with everyday life for a long period of time. Depression affects about 19 million Americans annually. It is estimated to contribute to half of all suicides. About 5%-10% of women and 2%-5% of men will experience at least one major depressive episode during their adult life. Depression affects people of all races, incomes, ages, and ethnic and religious backgrounds, but it is three to five times more common in the elderly than in young people.

• The exact cause of depression is not known. Many researchers believe it is caused by chemical imbalances in the brain, which may be hereditary or caused by events in a person's life.
• Some types of depression seem to run in families, but depression can also occur in people who have no family history of the illness. Stressful life changes or events can trigger depression in some people. Usually, a combination of factors is involved.
• Substance abuse: While it has long been believed that depression caused people to misuse alcohol and drugs in an attempt to make themselves feel better (self-medication), it is now thought that the reverse can also be the case; substance abuse can actually cause depression.

There is no single cause of major depression. Psychological, biological and environmental factors may all contribute to its development. Whatever the specific causes of depression, scientific research has firmly established that major depression is a biological, medical illness.

• Norepinephrine, serotonin and dopamine are three neurotransmitters (chemical messengers that transmit electrical signals between brain cells) thought to be involved with major depression.
• "Scientists have also found evidence of a genetic predisposition to major depression"Scientists believe that if there is a chemical imbalance in these neurotransmitters, then clinical states of depression result. Antidepressant medications work by increasing the availability of neurotransmitters or by changing the sensitivity of the receptors for these chemical messengers.
• Scientists have also found evidence of a genetic predisposition to major depression. There is an increased risk for developing depression when there is a family history of the illness. Not everyone with a genetic predisposition develops depression, but some people probably have a biological make-up that leaves them particularly vulnerable to developing depression.
• Some illnesses such as heart disease and cancer and some medications may also trigger depressive episodes.
• It is also important to note that many depressive episodes occur spontaneously and are not triggered by a life crisis, physical illness or other risks.

• Life events or situations, such as: Breaking up with a significant other, illness or death in the family, or parents divorcing (for adolescents)
• Repetitive traumatic calls
• Childhood events, such as abuse or neglect
• Divorce, death of a friend or relative, or loss of a job (for adults)
• Social isolation (common in the elderly)
• Medical conditions such as hypothyroidism (underactive thyroid), medications (such as sedatives and high blood pressure medications), cancer, major illness, or prolonged pain
• Sleeping problems, Sleep deprivation
• Alcohol or drug abuse

Agitation, restlessness, and irritability

Dramatic change in appetite, often with weight gain or loss

Extreme difficulty concentrating

Fatigue and lack of energy

Feelings of hopelessness and helplessness

Feelings of worthlessness, self-hate, and inappropriate guilt

Inactivity and withdrawal from usual activities, a loss of interest or pleasure in activities that were once enjoyed (such as sex)

Thoughts of death or suicide

Trouble sleeping or excessive sleeping

Depression can appear as anger and discouragement, rather than as feelings of hopelessness and helplessness. Use of alcohol or illegal substances may be more likely to occur.

Even Medicines that you take for other problems could cause or worsen depression, check with your doctor.

• Medicines that you take for other problems could cause or worsen depression. You may need to change them. DO NOT change or stop taking any of your medications without consulting your doctor.
• People who are so severely depressed that they are unable to function, or who are suicidal and cannot be safely cared for in the community may need to be treated in a psychiatric hospital.
• Most people benefit from antidepressant drug therapy, along with psychotherapy. As treatment takes effect, negative thinking diminishes. It takes time to feel better, but there are usually day-to-day improvements.

• Take medications correctly and learn how to manage side effects.
• Learn to watch for early signs that depression is becoming worse and know how to react when it does.
• Try to exercise more, seek out other activities that bring you pleasure, and maintain good sleep habits.
• Avoid alcohol and illegal drugs. These substances can make the depression worse over time, and may also impair your judgment about suicide.
• When struggling with your depression, talk to someone you trust about how you are feeling. Try to be around people who are caring and positive.
• Try volunteering or getting involved in group activities.

• Cognitive behavioral therapy teaches depressed people ways of fighting negative thoughts. People can learn to be more aware of their symptoms, learn what seems to make depression worse, and learn problem-solving skills.
• Psychotherapy can help someone with depression understand the issues that may be behind their behaviors, thoughts, and feelings.
• Joining a support group of people who are experiencing problems like yours can also help. Ask your therapist or doctor for a recommendation.

•Fava M, Cassano P. Mood disorders: Major depressive disorder and dysthymic disorder. In: Stern TA, Rosenbaum JF, Fava M, Biederman J, Rauch SL, eds. Massachusette General Hospital Comprehensive Clinical Psychiatry. 1st ed. Philadelphia, Pa: Mosby Elsevier; 2008:chap 29.

•American Psychiatric Association. Practice guidelines for the treatment of patients with major depressive disorder. 2nd ed. September 2007. Accessed January 22, 2010.

•Little A. Treatment-resistant depression. Am Fam Physician. 2009;80:167-172. [PubMed: 19621857]