Depression ranks among the leading causes of disability, morbidity, and mortality in young people (YP). Although the last decades have led to considerable progress in our understanding of the causes of mood problems in YP and in the development of effective treatments, limitations of current theoretical and intervention approaches have also become increasingly clear. First, with regard to diagnosis, there is a clear shift away from a categorical, disease-oriented model to a dimensional approach that focuses on underlying systems implicated in psychopathology. The Research Domain Criteria (RDoC) is a good example of this change in approach. Second, with regard to treatment, although a variety of effective interventions for pediatric depression have been developed, they are equally effective, response rates are relatively low, with a substantial number of YP dropping out of treatment and thus being “hard-to-reach”. Together, these findings force us to ask the “hard questions” about our views concerning the nature of depression and its treatment in YP.
Based on evolutionary biological and developmental psychopathology considerations, we present an integrative developmental cascade model of depression that essentially suggests that depression emerges out of a three-pronged series of interacting impairments in the domains of stress regulation, reward, and mentalizing (SRM).
We also focus on how this model may explain in large part the heterogeneity and thus marked comorbidity of depression with other psychiatric disorders, as well as with functional somatic and somatic disorders.
We outline the implications for the development, evaluation, training and dissemination of interventions for YP with depression.

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