Depression, in most cases, is caused by a combination of multiple factors. These factors can include genetic susceptibility, live events, environmental stress, and psychodynamic considerations.

Biological Factors

• Neurotransmitter Disturbances
  Norepinephrine and serotonin are the two neurotransmitters most implicated in mood disorders. Dopamine is also thought to play a role.
• Hormonal Dysregulation
  Approximately 5 to 10 percent of depression patients have previously undetected thyroid dysfunction.
• Sleep Neurophysiology
  Depression is associated with a premature loss of deep (slow-wave) sleep and in increase in sleep awakening at night.
• Neuroanatomical Considerations
  Modern neuroscience focuses on four regions of the brain responsible for the regulation of normal emotions: the prefrontal cortex, the anterior cingulate, the hippocampus, and the amygdala. Physical trauma to the brain, therefore, could be a factor in depression.• Immunological Issues
  Depressive disorders are associated with several immunological abnormalities. (More info in Q&A)

Genetic Factors
Studies indicate that if one parent has a mood disorder, such as major depressive disorder, their child will have a 10 to 25 percent risk for a mood disorder. If both parents are affected, the risk for their child approximately doubles. In addition, the more members of a family that are affected by a mood disorder the greater the risk is to a child.

Studies of twins provide evidence that genes account for 50 to 70 percent of genetic mood disorders. Environmental or other factors are thought to account for the remainder. Studies show that the rate of mood disorders shared by twins is higher among identical twins (70 to 90 percent) than among fraternal twins (16 to 35 percent).

Psychosocial Factors

• Life Events and Environmental Stress
  Stressful life events are shown to more often precede first, rather than subsequent, episodes of depression. One theory is that the stress accompanying the first episode of depression results in long-lasting changes in the brain’s biology, which may alter neurotransmitter functioning. As a result, a person is at risk for experiencing subsequent episodes of depression, even without an external stressor. Some experts believe that life events play the primary role in depression. The strongest evidence to support this theory is when children under the age of 11 lose a parent and experience major depression. Losing a spouse is the life event most often associated with the onset of depression. Another risk factor is unemployment. People who are out of work are three times more likely to report symptoms of major depression than those who are employed.
• Personality Factors
  There is no evidence that any particular personality type or trait predisposes a person to depression. All people, of any personality type, can and do become depressed under appropriate circumstances, such as job loss, traumatic events, major life change, loss of a loved one, persistent abuse by another, or drug/substance abuse.
• Psychodynamic Factors
  Psychodynamic factors take into account the unconscious psychological forces that impact a person’s psychological development. When it comes to depression, there are several different psychodynamic theories. Theories range from a disturbed infant-mother relationship (Sigmond Freud), an expression of aggression toward loved ones (Melanie Klein), living for someone else rather than oneself (Silvano Arieti), an expression of powerlessness (Edith Jacobson), a lack of self-esteem due to emotional needs unmet by parents (Heinz Kohut), traumatic separation during childhood or damaged early attachments (John Bowlby).

Cognitive Theory
The cognitive theory asserts that depression can develop in individuals with cognitive distortions (inaccurate thoughts), such as negative perceptions towards themselves, the world, and their future (Aaron Beck). Depressed patients may have cognitive distortions, drawing a specific conclusion without sufficient evidence. They may also focus on a single detail while ignoring other, more important aspects of an experience. Likewise, they may form conclusions based on limited experience, or they may overvalue or undervalue the significance of a particular event.

Learned Helplessness
The learned helplessness theory connects depression to the experience of uncontrollable events. Adverse external events cause a loss of self-esteem, leading to depression. Behaviorists who subscribe to this theory believe that improving one’s depression in such a case depends on the patient learning a sense of control and mastery of one’s environment.