L-dopa modulates striatal functional connectivity in adults with psychotic-like experiences: A randomized double-blind placebo-controlled study

Abstract

IntroductionAccording to the dopamine hypothesis functional brain abnormalities and neurochemical alterations may converge to cause psychosis through aberrant salience attribution. Indeed, resting-state functional magnetic resonance imaging (rs-fMRI) has revealed widespread brain disconnectivity across the psychotic spectrum.ObjectivesTo advance the understanding of the dopaminergic involvement in intrinsic functional connectivity (iFC) and its putative relationship to the development of psychotic disorders we aimed to investigate the link between L-Dopa, a dopamine precursor, and its modulation of striatal iFC in subthreshold psychosis, i.e. non-clinical psychosis.MethodsWe used a randomized, double-blind placebo controlled study design including in our sample 56 healthy, male, right-handed, subjects with no familiar risk factors for psychosis who were assessed with the Schizotypal Personality Questionnaire (SPQ) and underwent 10 minutes of rs-fMRI scanning. All subjects received either 250 mg of Madopar DR®(200 mg L-Dopa plus 50 mg benserazid, dual release form) or a placebo. We analysed resting-state iFC of 6 striatal seeds, known to evoke dopamine related networks.ResultsThe main effect of L-Dopa presented itself (FWE-corrected) as a significant decrease in iFC from the right ventral striatum to the cerebellum and the precuneus cortex, and an increase in iFC to the occipital cortex. Subjects with high SPQ positive symptom sub-scores showed a significant increase of L-Dopa induced connectivity.ConclusionWe identified striatal functional connectivity being modulated by augmented dopamine availability, and in support of the dopamine hypothesis, we found that those iFC patterns are associated to high scores of psychotic like experiences.Disclosure of interestThe authors have not supplied their declaration of competing interest.