Sodium nitroprusside as an adjunctive treatment for schizophrenia reduces Ndel1 oligopeptidase activity

To assess nuclear distribution element-like 1 (Ndel1) enzyme activity following acute administration of sodium nitroprusside (sNP) in a rodent model of schizophrenia (SCZ) and in a cohort of chronic SCZ patients. Ndel1 activity was measured following sNP infusions in spontaneously hypertensive rats (SHR) (2.5 or 5.0 mg/kg) and in a double-blind randomized trial with 15 SCZ patients (0.5 µg/kg/min). Patients were randomized into two groups (group I: n=7; group II: n=8), with one group receiving placebo and the other sNP in phase A. In phase B, the groups switched treatments. sNP was administered as an infusion of 0.5 µg/kg/min, for 4 h, while placebo was a 5% glucose solution infused under the same conditions. The infusions were administered once weekly over 4 weeks. Psychopathology was assessed using the 18-item figure 5 (BPRS-18 - Bech's version) and the negative subscale of the Positive and Negative Syndrome Scale. Ndel1 activity was significantly reduced after sNP infusion in SHR and in patients receiving sNP (t = 7.756, degrees of freedom [df] = 97, p < 0.0001, dcohen=1.44) compared to placebo. Reduced Ndel1 activity from baseline to the end of infusion was only seen in patients after treatment with sNP. SCZ patients may benefit from adjunctive therapy with sNP and that the Ndel1 enzyme is a candidate biomarker of psychopathology in the disorder. Future research should look into the role of Ndel1 in SCZ and the potential effects of sNP and drugs with similar profiles of action in both animals and patients.