Adolescent development is accompanied by the emergence of a population-wide increase in vulnerability to depression that is maintained through adulthood. We provide a model for understanding how this vulnerability to depression arises, and why depression is so often precipitated by social rejection or loss of status during this phase. There is substantial remodeling and maturation of the dopaminergic reward system and the prefrontal cortex during adolescence, that coincides with the adolescent entering the complex world of adult peer and romantic relationships, where the rewards that can be obtained (feelings such as belonging, romantic love, status and agency) are abstract and temporally distant from the proximal context. Development of the prefrontal cortex makes it possible to pursue such complex and distal rewards, which are, however, tenuous and more readily frustrated than more immediate rewards. We hypothesize that when these distant rewards are frustrated they suppress the reward system, and that when such suppression is extensive and occurs for long enough, the clinical picture that results is one of depression.