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It is estimated that 16% of the general population experiences clinically significant depression in a given 12-month period (Kessler, Tat Chiu, Demler, & Walters, 2005). In addition to the impact on affected individuals and their families, depressive disorders place a burden of almost $50 billion per year on the American economy, accounting for over 20% of costs for all mental illness (Stewart, Ricci, Chee, Hahn, & Morganstein, 2003). Compared to other physical and mental disorders, depression is the leading cause of disability worldwide according to the World Health Organization (James et al., 2018). Given the substantial personal and societal costs of this disorder, efforts to identify vulnerability factors and effective interventions for depression are particularly important. Our goal in this chapter is to present basic psychopathology research in depression and to discuss the treatment implications of these findings. Though all depressive disorders share similar features (Gotlib & LeMoult, 2014), there are some important differences between diagnostic categories that are not covered in this chapter. Instead, we focus here on depressive symptoms in general and major depressive disorder (MDD) in particular. We first describe the phenomenology of depression, including its associated clinical features and course. We then discuss the etiology of depression and focus in particular on novel empirical findings. After each section, we address the clinical implications of the findings. This is a timely and important task because, even though effective depression treatments exist, these interventions have undergone few changes in the past decades, and rates of recurrence of depression are still high even after successful treatment. C H A P T E R 2