BackgroundPsychotic symptoms have been linked to salience abnormalities in the brain reward system, perhaps caused by a dysfunction of the dopamine neurotransmission in striatal regions. Blocking dopamine D₂ receptors dampens psychotic symptoms and normalises reward disturbances, but a direct relationship between D₂ receptor blockade, normalisation of reward processing and symptom improvement has not yet been demonstrated. The current study examined the association between blockade of D₂ receptors in the caudate nucleus, alterations in reward processing and the psychopathology in a longitudinal study of antipsychotic-naïve first-episode schizophrenia patients.MethodsTwenty-two antipsychotic-naïve first-episode schizophrenia patients (10 males, mean age 23.3) and 23 healthy controls (12 males, mean age 23.5) were examined with single-photon emission computed tomography using ¹²³I-labelled iodobenzamide. Reward disturbances were measured with functional magnetic resonance imaging (fMRI) using a modified version of the monetary-incentive-delay task. Patients were assessed before and after 6 weeks of treatment with amisulpride.ResultsIn line with previous results, patients had a lower fMRI response at baseline (0.2 ± 0.5 v. 0.7 ± 0.6; p = 0.008), but not at follow-up (0.5 ± 0.6 v. 0.6 ± 0.7), and a change in the fMRI signal correlated with improvement in Positive and Negative Syndrome Scale positive symptoms (ρ = -0.435, p = 0.049). In patients responding to treatment, a correlation between improvement in the fMRI signal and receptor occupancy was found (ρ = 0.588; p = 0.035).ConclusionThe results indicate that salience abnormalities play a role in the reward system in schizophrenia. In patients responding to a treatment-induced blockade of dopamine D₂ receptors, the psychotic symptoms may be ameliorated by normalising salience abnormalities in the reward system.