Depression is a mood disorder that affects the way you think, feel, and behave. It causes feelings of sadness or hopelessness that can last anywhere from a few days to a few years. This is different than being upset about a minor setback or disappointment in your day.

Some people may experience mild depression only once in their lives, while others have several severe episodes over their lifetime. This more serious, long-lasting and intense form of depression is known as major depressive disorder (MDD). It may also be referred to as clinical depression or major depression.

The symptoms of MDD significantly interfere with daily activities, such school, work, and social events. They also impact mood and behavior as well as various physical functions, such as sleep and appetite. To be diagnosed with MDD, you must display five or more of the following symptoms at least once a day over the course of two weeks:

  • persistent feelings of sadness and hopelessness
  • lack of interest in doing most activities, including those you once enjoyed
  • decrease or increase in appetite accompanied by extreme weight loss or weight gain
  • sleeping too much or too little
  • restlessness
  • fatigue
  • excessive or inappropriate feelings of guilt or worthlessness
  • difficulty making decisions, thinking, and concentrating
  • multiple thoughts of death or suicide
  • a suicide attempt

People of any age may develop MDD, but the average age of onset is 32. According to the Depression and Bipolar Support Alliance, approximately 14.8 million American adults, or 6.7 percent of the United States population over age 18, are affected by MDD every year. The disorder also occurs in about one in 33 children and one in eight teens. In both children and adults, MDD may be treated with psychological counseling, antidepressant medication, or a combination of both therapies.

Researchers don’t know exactly why some people develop MDD, but they believe the following factors may play a role:

  • genetics: It appears that people with a family history of MDD are more likely to develop the disorder than others.
  • stress: A stressful life event, such a divorce or death of a loved one, can trigger an episode of MDD.
  • biochemical reactions: Chemicals in the brains of people with MDD seem to function differently than those in the brains of those without the disorder.
  • hormone imbalances: Changes in the balance of hormones may trigger MDD in certain people, especially during menopause or during and after pregnancy.

There are three parts of the brain that appear to play a role in MDD: the hippocampus, amygdala, and prefrontal cortex.

The hippocampus is located near the center of the brain. It stores memories and regulates the production of a hormone called cortisol. The body releases cortisol during times of physical and mental stress, including during times of depression. Problems can occur when excessive amounts of cortisol are sent to the brain due to a stressful event or a chemical imbalance in the body. In a healthy brain, brain cells (neurons) are produced throughout a person’s adult life in a part of the hippocampus called the dentate gyrus. In people with MDD, however, the long-term exposure to increased cortisol levels can slow the production of new neurons and cause the neurons in the hippocampus to shrink. This can lead to memory problems.

The prefrontal cortex is located in the very front of the brain. It is responsible for regulating emotions, making decisions, and forming memories. When the body produces an excess amount of cortisol, the prefrontal cortex also appears to shrink.

The amygdala is the part of the brain that facilitates emotional responses, such as pleasure and fear. In people with MDD, the amygdala becomes enlarged and more active as a result of constant exposure to high levels of cortisol. An enlarged and hyperactive amygdala, along with abnormal activity in other parts of the brain, can result in disturbances in sleep and activity patterns. It can also cause the body to release irregular amounts of hormones and other chemicals in the body, leading to further complications.

Many researchers believe high cortisol levels play the biggest role in changing the physical structure and chemical activities of the brain, triggering the onset of MDD. Normally, cortisol levels are highest in the morning and decrease at night. In people with MDD, however, cortisol levels are always elevated, even at night.

Experts have found that balancing the amount of cortisol and other chemicals in the brain can help reverse any shrinkage of the hippocampus and treat the memory problems it may cause. Correcting the body’s chemical levels can also help reduce symptoms of MDD.

There are several common medications that can fight the negative effects of depression on the brain by helping to balance the chemicals in the brain. These include:

  • selective serotonin uptake inhibitors (SSRIs): These drugs can help alleviate symptoms of MDD by changing the levels of a chemical called serotonin in the brain. Examples of SSRIs include fluoxetine (Prozac), paroxetine (Paxil), and citalopram (Celexa).
  • serotonin-norepinephrine reuptake inhibitors (SNRIs) and tricyclic antidepressants: When used together, these medications can relieve MDD symptoms by altering the amounts of serotonin and norepinephrine in the brain. These chemicals help boost mood and energy levels. Examples of SNRIs include duloxetine (Cymbalta) and venlafaxine (Effexor XR). Imipramine (Tofranil), nortriptyline (Pamelor), and trimipramine (Surmontil) are examples of tricyclic antidepressants.
  • norepinephrine-dopamine reuptake inhibitors (NDRIs): These medications aid people with MDD by increasing levels of the mood-boosting chemicals norepinephrine and dopamine in the brain. Bupropion (Wellbutrin) is a type of NDRI that may be used.
  • monoamine oxidase inhibitors (MAOIs): These drugs help ease symptoms of MDD by increasing the amount of norepinephrine, serotonin, and dopamine in the brain. They can also improve brain cell communication
  • atypical antidepressants: This group of medications includes tranquilizers, mood stabilizers, and antipsychotics. These drugs can block brain cell communication in order to relax the body.

Besides medications, certain medical procedures can also affect the brain to help ease symptoms of MDD. These include:

  • electroconvulsive therapy (ECT), which involves passing electrical currents through the brain to boost communication between brain cells
  • transcranial magnetic stimulation (TMS), which involves sending electrical pulses into the brain cells that regulate mood

Researchers also believe that psychotherapy can alter brain structure and help relieve MDD symptoms. Specifically, psychotherapy appears to strengthen the prefrontal cortex.

There are other ways to boost brain health and help recover from MDD without medical intervention. These include:

  • eating healthful foods and staying active, which stimulates brain cells and strengthens communication between brain cells
  • sleeping well, which helps grow and repair brain cells
  • avoiding alcohol and illegal drugs, which can destroy brain cells

Talk to your doctor about which treatments may be best for you.