Effects of sodium nitroprusside on the default mode network of patients with schizophrenia and healthy controls

Brain default mode network (DMN) function is altered in schizophrenia (SZ). Considering the roles of nitrergic and glutamatergic transmission in SZ neurobiology, supplementation with nitric oxide (NO) donors such as sodium nitroprusside (SNP) has been proposed as a means of reducing symptoms, but results have been mixed and potential mechanisms remain unclear. In this context, we sought to investigate the effects of SNP on DMN functional connectivity (FC) assessed by functional magnetic resonance imaging (fMRI) in SZ patients and healthy controls.

In an open-label trial, participants were divided into three treatment groups to receive intravenous SNP (0.25 µg/kg/min over 12 minutes): SZ patients on clozapine (CLZ) (n=13), SZ patients on non-CLZ antipsychotics (n=13), and controls (n=14). fMRI data was collected continuously before, during, and after SNP infusion. Symptom changes were evaluated with the Brief Psychiatric Rating Scale (BPRS).

Considering only patient groups at baseline, there was no difference in connectivity. When comparing all patient groups to controls, patients exhibited increased activity in DMN subregions and increased FC in the left supramarginal gyrus. During SNP infusion, FC was increased in the left angular gyrus; immediately following infusion, FC increased in the bilateral medial temporal gyri and left supramarginal gyrus of patients compared to controls. There were no significant differences between patient groups at any time point, nor changes in symptoms.

Although our results are preliminary, this work demonstrated for the first time that SNP modulates brain connectivity in healthy controls and patients with SZ. Future research is warranted to confirm these findings.