The role of the brain reward system in depression

1. The goal of this review is to familiarize the reader about the potential involvement of the brain reward system (BRS) in symptoms of Major Depressive Disorder (MDD). The authors introduce a novel approach to study the pathophysiology of MDD that includes pharmacological probing of BRS pathways (e.g. d-amphetamine, hydromorphone) together with an elicited and measurable behavioral component (e.g. pleasant effects, increased energy, altered cognition). 2. To this date, the major focus of MDD pathophysiology studies has been to characterize biological differences between healthy subjects and depressed patients such as alteration in the monoaminergic and endocrine systems. The relative importance of the various biological changes has not been elucidated, that is, linking these with specific behavioral manifestations in MDD have rarely been attempted. 3. One core symptom of MDD is a decreased experience of pleasure or interest in previously enjoyed activities (i.e. anhedonia) such as work or hobbies, and is accompanied by decreased motivation or drive. The BRS consists of the neural pathways involved in eliciting rewarding experiences in animals and humans. 4. The hypothesis is that altered BRS function may be an underlying brain mechanism of the loss of pleasure/interest experienced in MDD, and will be manifested through an altered response to a BRS probe. The authors have examined BRS function in MDD by introducing a pharmacological probe (i.e. d-amphetamine/d-amph). Amphetamine is defined as a probe due to its ability to release dopamine within major components of the BRS (i.e. the mesocorticolimbic dopamine system.) In addition to the objective pharmacological effects (e.g, altered heart rate), BRS probes like d-amph elicit reliable and measurable behavior, that is, the hedonic effects. 5. A review of the neurobiology of MDD, the BRS, the rationale for implicating the BRS in depressive symptoms, and preliminary data, are presented in this article.