Major depressive disorder (MDD), particularly with recurring episodes, is characterized by decreased striatal dopamine transporter (DAT) expression, which may reflect a compensatory downregulation due to low dopamine (DA) signalizing within mesolimbic pathways. This according to a cross-sectional positron emission topography (PET) study that enrolled consecutive individuals with MDD who were not taking medication and who were demographically matched to healthy controls. Striatal and midbrain DAT binding potential was assessed. Researchers found:
- Compared with 23 healthy controls, 25 individuals with MDD showed significantly lower in vivo DAT availability in the bilateral putamen and ventral tegmental areas, and both reductions were exacerbated with increased numbers of depressive episodes.
- The MDD group failed to show an age-associated reduction in striatal DAT availability.
- DAT availability in the ventral tegmental area was lowest in individuals with MDD who reported feeling trapped in stressful circumstances.
Pizzagalli DA, Berretta S, Wooten D, et al. Assessment of striatal dopamine transporter binding in individuals with major depressive disorder: In vivo positron emission tomography and postmortem evidence. [Published online ahead of print May 1, 2019]. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2019.0801.
This paper by Pizzagalli et al. suggests that certain major depressive disorder (MDD) patients have low levels of dopamine transporters (DAT) and posit this may occur as a result of poor dopamine neurotransmission. Essentially, as dopamine activity lowers (possible etiology of MDD), there may be less need for DAT. In this specific subset of patients, and thinking of clinical application, we might theorize that blocking DAT then with an antidepressant such as bupropion may not be effective. Using an off label amphetamine at higher doses might alter the VMAT2 system to allow greater synaptic dopamine release or use of a D2/D3 dopamine receptor partial agonist might be able to improve dopamine neurotransmission to alleviate MDD. If DAT is not a great target translationally in these patients, a psychopharmacologist may think of other ways to enhance dopaminergic neurocircuitry in hopes of lowering MDD symptoms. —Thomas L. Schwartz, MD; Senior Associate Dean of Education, Interim Chair/Professor of Psychiatry, SUNY Upstate Medical University.