Dopamine Release in Antidepressant-Naive Major Depressive Disorder: A Multimodal [11C]-(+)-PHNO Positron Emission Tomography and Functional Magnetic Resonance Imaging Study

[11C]-(+)-PHNO demonstrated high sensitivity to displacement by amphetamine-induced dopamine release, but dopamine release capacity and D2/D3 availability were not associated with ventral striatal activation to reward prediction error or clinical features, in this study powered to detect large effects. While a preponderance of indirect evidence implicates dopaminergic dysfunction in MDD, these findings suggest that presynaptic dopamine dysregulation may not be a feature of MDD or a prerequisite for treatment response to dopamine agonists.