Individual differences in dopamine-related traits influence mood effects of dopamine D2-antagonist and antidepressant treatment expectations

Background: High trait anhedonia and low trait extraversion have both been previously related to not only low state positive affect but also depressive disorders, disrupted reward processing, and altered mesolimbic dopaminergic signaling. Research on placebo responses suggests that treatment expectations may alter dopamine signaling, elevate positive affect, and reduce depressive symptoms in anhedonic individuals. However, it remains unclear whether such antidepressant placebo responses depend on putative low baseline dopaminergic functioning in high anhedonia and low extraversion. The present study investigates how interindividual differences in these traits influence positive affective responses under manipulation of dopamine and treatment expectations.Materials and Methods: In a randomized, double-blind 2×2 design (N = 297), we administered either placebo or the dopamine D2 receptor antagonist sulpiride (400 mg), and manipulated treatment expectations by telling participants that they received either a mood-elevating drug or an inactive substance. Moreover, we assessed trait anhedonia and extraversion, and had participants rate state positive affect at 6 different time points before and after treatment.Results: Trait anhedonia and extraversion, as well as a broad trait positive affectivity factor, predicted state positive affect across time points. Importantly, effects of sulpiride and antidepressant treatment expectations on positive affect were moderated by dopaminergic traits such that sulpiride increased state positive affect in high anhedonia but decreased it in low anhedonia. Similarly, antidepressant treatment expectations raised positive affect in low extraversion but reduced it in high extraversion. Conclusions: This study demonstrates that dopamine-related individual differences moderate the effects of both sulpiride and a placebo intervention on positive affective state.