Dopamine challenge reduces mental state attribution accuracy

Abstract Difficulties in reasoning about others’ mental states (i.e., mentalising / Theory of Mind) are highly prevalent among disorders featuring dopamine dysfunctions (e.g., Parkinson’s disease) and significantly affect individuals’ quality of life. However, due to multiple confounding factors inherent to existing patient studies, currently little is known about whether these socio-cognitive symptoms originate from aberrant dopamine signalling or from psychosocial changes unrelated to dopamine. The present study therefore investigated the role of dopamine in modulating mentalising in a sample of healthy volunteers. We used a double-blind, placebo-controlled procedure to test the effect of the D2 antagonist haloperidol on mental state attribution, using an adaptation of the Heider & Simmel (1944) animations task. On two separate days, once after receiving 2.5mg haloperidol and once after receiving placebo, 33 healthy adult participants viewed and labelled short videos of two triangles depicting mental state (e.g., surprising) and non-mental state (e.g., following) interactions. Using Bayesian mixed effects models we observed that haloperidol decreased accuracy in labelling both mental- and non-mental state animations. Our secondary analyses suggest that dopamine modulates inference from mental- and non-mental state animations via independent mechanisms, pointing towards two putative pathways underlying the dopaminergic modulation of mental state attribution: Action representation and a shared mechanism supporting mentalising and emotion recognition. We conclude that dopamine is causally implicated in Theory of Mind. Our results have implications for the neurochemical basis of socio-cognitive difficulties in patients with dopamine dysfunctions and generate new hypotheses about the specific dopamine-mediated mechanisms underlying social cognition.