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The theory of constructed emotion is a systems neuroscience approach to understanding the nature of emotion. It is also a general theoretical framework to guide hypothesis generation for how actions and experiences are constructed as the brain continually anticipates metabolic needs and attempts to meet those needs before they arise (termed allostasis). In this review, we introduce this framework and hypothesize that allostatic dysregulation is a trans-disorder vulnerability for mental and physical illness. We then review published findings consistent with the hypothesis that several symptoms in major depressive disorder (MDD), such as fatigue, distress, context insensitivity, reward insensitivity, and motor retardation, are associated with persistent problems in energy regulation. Our approach transforms the current understanding of MDD as resulting from enhanced emotional reactivity combined with reduced cognitive control and, in doing so, offers novel hypotheses regarding the development, progression, treatment, and prevention of MDD.