Functional Connectivity Between Auditory and Medial Temporal Lobe Networks in Antipsychotic-Naïve Patients With First-Episode Schizophrenia Predicts the Effects of Dopamine Antagonism on Auditory Verbal Hallucinations

Understanding how antipsychotic medication ameliorates auditory verbal hallucinations (AVH) through modulation of brain circuitry is pivotal for understanding the pathophysiology of psychosis and for predicting treatment response. This case-control study included examinations at baseline and at follow up after six weeks. Initially antipsychotic-naïve first-episode schizophrenia experiencing AVH was recruited together with healthy controls. Antipsychotic treatment with the relatively selective D2 receptor antagonist amisulpride was administered as monotherapy. Functional connectivity measured by resting state functional magnetic resonance imaging between networks of interest was used to study the effects of D2 blockade on brain circuitry and to predict clinical treatment response. Hallucinations were rated with the Positive and Negative Syndrome Scale (PANSS). Thirty-two patients experiencing AVH and 34 healthy controls were scanned at baseline. Twenty-two patients and 34 healthy controls were re-scanned at follow up. Connectivity between the auditory network and the medial temporal lobe network was increased in patients at baseline (p = 0.002) and normalized with six weeks of D2 blockade (p = 0.018). At baseline, the connectivity between these networks were positively correlated with ratings of hallucinations (t = 2.67; p = 0.013). Moreover, baseline connectivity between auditory network and the medial temporal lobe network predicted reduction in hallucinations (t = 2.34; p = 0.032). Functional connectivity between auditory network and medial temporal lobe predicted response to initial antipsychotic treatment. These findings demonstrate that connectivity between networks involved in auditory processing, internal monitoring and memory are associated with the clinical effect of dopamine antagonism.