SLC6A4 and major depressive disorder: While patients suffering from depression and anxiety will not possess every SNP, transcript or protein change, we speculate that any of these changes could result in decreased endocytosis of 5-HT1A and 5-HT2A, disrupting their typical plasma membrane and endosomal signaling profiles (Figure 3A), or enhance clathrin-independent endocytosis and recycling of SERT or decrease SERT CME, increasing its levels at the plasma membrane (Figure 3B), which would deplete extracellular serotonin levels to further reducing serotonin signaling.