There is a risk for developing depression when there is a family history, indicating that a biological vulnerability can be inherited. The risk may be somewhat higher for those with bipolar depression. However, not everybody with a genetic vulnerability develops the illness. Apparently additional factors, possibly a stressful environment and other psychosocial factors are involved in the onset of depression.

Though major depression seems to occur, generation after generation, in some families, it can also occur in people who have no family history of depression. Whether the disease is inherited or not, it is evident that individuals with major depressive illness often have too little or too much of certain neurochemicals.

Psychological makeup also plays a role in vulnerability to depression. People who have low self-esteem, who consistently view themselves and the world with pessimism, or who are readily overwhelmed by stress are prone to depression.

A serious loss, chronic illness, difficult relationship, financial problem or any unwelcome change in life patterns can also trigger a depressive episode. Very often, a combination of genetic, psychological, and environmental factors is involved in the onset of a depressive illness.