While PET studies using TSPO ligands in other disease states (e.g., Alzheimer’s disease) have reference regions that may be used instead of arterial sampling [44], the universal increases in TSPO binding observed in unmedicated MDD subjects indicate that no reference region exists in the brain and that arterial sampling will be required to measure differences between patients and controls. This evidence concerns the gene TSPO and early-onset autosomal dominant Alzheimer disease.