Until now, depression research has taken a surprisingly narrow approach to modelling the disease, mainly focusing on some form of psychomotor retardation within a mechanistic framework of depression etiology. However, depression has many symptoms and each is associated with a vast number of substrates. Thus, to deepen our insights, this SI ("Depression Symptoms") reviewed the behavioral and neurobiological sequelae of individual symptoms, specifically, psychomotor retardation, sadness, low motivation, fatigue, sleep/circadian disruption, weight/appetite changes, and cognitive affective biases. This manuscript aims to integrate the most central information provided by the individual reviews. As a result, a dynamic model of depression development is proposed, which views depression as a cumulative process, where different symptoms develop at different stages, referred to as early, intermediate, and advanced, that require treatment with different pharmaceutical agents, that is, selective serotonin reuptake inhibitors early on and dopamine-based antidepressants at the advanced stage. Furthermore, the model views hypothalamic disruption as the source of early symptoms and site of early intervention. Longitudinal animal models that are capable of modelling the different stages of depression, including transitions between the stages, may be helpful to uncover novel biomarkers and treatment approaches.
Keywords: Animal model; Depression; Hypothalamus; Orexin; Stress; Symptomatology.
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