• Etiological models for depression are largely diathesis-stress models in which stressful experiences trigger depression in those who may be vulnerable due to biological and psychosocial characteristics and circumstances.

• Environmental stressors associated with depression include acute life events, chronic stress, and childhood exposure to adversity. Personal vulnerabilities associated with depression include cognitive, interpersonal, and personality factors.

• Biological, environmental, and personal vulnerabilities interact to contribute to the development of depression and also may be affected by depressive states in a bidirectional process.

• Depression rarely occurs independent of other psychological disorders, including anxiety, substance abuse, behavioral, and personality disorders, as well as other medical illnesses. The presence of co-occurring psychological and medical disorders exacerbates the clinical and social consequences of depression, and makes it more challenging to treat.

• Certain biological, environmental, and personal factors have also been associated with the protection from or the overcoming of risk factors and adverse conditions related to the development of depression.

The purpose of this chapter is to review what is known or suspected about the causes of depression. Fundamentally, such depressive symptoms as sad mood, pessimism, and lethargy, are universal human experiences and are considered normal reactions to the struggles, disappointments, and losses of everyday life. However, for some individuals, the intensity and persistence of depressive symptoms are not typical, and a challenge for researchers has been to understand why some individuals experience marked and enduring depressive reactions and others do not. This chapter discusses some of the characteristics of individuals that may make them vulnerable, as well as the features of environments that are particularly likely to provoke depression. The chapter also emphasizes the interplay between persons