Effects of Sodium Nitroprusside on the Default Mode Network of Schizophrenia Patients and Healthy Controls.

Objective: Schizophrenia patients present poorer social cognition skills related to altered default mode network (DMN) functioning. In this context, glutamate NMDA receptors is relevant, alongside the supplementation with a nitric oxide (NO) donor such as sodium nitroprusside.

Methods: This investigation concerned sodium nitroprusside's effects on schizophrenia patients' brain DMN functional connectivity using fMRI. In this open-label trial, we administered a 0.25 μg/kg/min sodium nitroprusside infusion over 12 minutes in three treatment groups: patients taking clozapine (n = 13), patients taking other antipsychotics than clozapine (n = 13), and healthy controls (n = 14). Functional MRI data was collected continuously before, during, and after sodium nitroprusside infusion. Symptom changes were evaluated with the Brief Psychotic Rating Scale.

Results: Considering only patient groups at baseline, there was no difference in connectivity. When comparing all patients to controls, patients presented increased activity in sub-regions of the default mode network and increased functional connectivity in the left supramarginal gyrus. During sodium nitroprusside infusion, there was greater functional connectivity in the left angular gyrus. Immediately after treatment, increased functional connectivity in the bilateral medial temporal gyrus and the left supramarginal gyrus was found in patients compared to controls. There were no significant differences between patient groups in any timepoint or changes in symptoms.

Conclusions: Although the results presented are preliminary, composing of a small sample and dosage, this work demonstrated for the first time that sodium nitroprusside modulates brain connectivity in healthy controls and patients with schizophrenia. Future research is warranted to confirm these findings.