Pizzagalli DA, Berretta S, Wooten D, et al. - Via a cross-sectional study that investigated positron emission tomography in 25 individuals with major depressive disorder (MDD) and 23 healthy controls and postmortem data in 15 individuals with MDD and 14 healthy controls, researchers examined the striatal dopamine transporter binding in individuals with MDD and assessed in postmortem tissues from donors with MDD who died by suicide. In contrast with 23 healthy controls, 25 individuals with MDD demonstrated significantly lower in vivo DA transporter (DAT) availability in the bilateral putamen and ventral tegmental area, and both decreases were intensified with rising numbers of depressive episodes. The MDD group failed to exhibit an age-associated decrease in striatal DAT availability, with young individuals with MDD being imperceptible from elderly healthy controls, unlike healthy controls. Furthermore, in people with MDD who reported feeling trapped in stressful situations, DAT availability in the ventral tegmental area was least. Lower DAT levels (and tyrosine hydroxylase) in the putamen of MDD vs healthy controls were replicated in postmortem analyses. In conclusion, major depressive disorder, particularly with recurring episodes, was identified by reduced striatal DAT expression, which might highlight a compensatory downregulation because of low DA signaling within mesolimbic pathways.