ABSTRACT
The magnitude of evidence supporting a role for the serotonin neurotransmitter system in major depressive disorder (MDD) has been forthcoming over the past ˜ve decades and is indispensable to our understanding of this complex and heterogeneous illness. In this chapter, we will explore the historical perspectives that led to the monoamine hypothesis of depression and, speci˜cally, the ideas regarding the role of serotonin in the etiology and pathophysiology of depression. We will present recent views on factors in¡uencing susceptibility to depression, including the discovery of gene polymorphisms in humans and studies focused on the developmental sensitivity of the serotonin system, which provide approaches to unraveling the complexity of depression. Additionally, investigations on the mechanisms of action of different classes of antidepressant drugs have also contributed insight into the role of serotonin in depression. Finally, we will touch on peripheral biomarkers of the central serotonin system that might lead to personalized medicine approaches to improve therapeutic outcomes.
