Preclinical and clinical evidence suggests that 5-HT4R levels are sensitive to serotonergic manipulations in healthy controls such that higher synaptic serotonin, lower 5-HT4R (Haahr et al., 2014); however, this is not necessarily the case in depression and does not necessarily translate to absolute 5-HT4R levels in stable conditions. Here, HTR4 is linked to major depressive disorder.