Serotonin receptors in depression: from A to BDespite the relative success in treating depression by increasing extracellular serotonin, there is a lack of strong evidence supporting a direct correlation between low serotonin signaling and depression. While some studies report an association between levels of platelet serotonin and depression, this has not been a consistent finding in large sample sets, and it is also unclear how platelet levels are related to brain levels of serotonin 10, 11. Additionally, few studies report direct correlations between cerebrospinal fluid 5-hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite, and depression 12, 13. Low levels of tryptophan have been consistently linked to depression; however, these effects could be independent of serotonin 14, 15. The lack of consistent clear-cut abnormalities in global measures of serotonin signaling isn’t surprising if one considers the complexity of the receptors at which serotonin binds, the intricate neuroanatomical circuitry of the serotonin system, and the developmental role serotonin plays as a neurotrophic factor 16– 18. Many recent studies have focused on understanding the mechanisms through which serotonin affects depression by studying the impact of 5-HTT and the 15 known receptors through gene-association studies, human brain imaging, and pharmacological and genetic mouse models 19.