According 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.

To 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.

We 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.

The 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.

We 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.

The authors have not supplied their declaration of competing interest.