A Novel Biomarker Renalase and Its Relationship with its Substrates in Schizophrenia

J Med Biochem. 2019 May 11;38(3):299-305. doi: 10.2478/jomb-2018-0031. eCollection 2019 Jul.

Abstract

Background: Schizophrenia, particularly the form related to excessive dopamine (DA), is a chronic psychotic disorder affecting millions of people worldwide. Renalase metabolizes its catecholamine (CA) substrates, including DA, suggesting that there might be an association between renalase levels and schizophrenia occurrence. Therefore, the current study aimed to evaluate the renalase and CA levels in the serum of patients with schizophrenia.

Methods: The study was conducted with thirty-three schizophrenia patients and an age- and gender-matched group of thirty-one controls. Renalase and CA levels were measured by using an enzyme-linked immunosorbent assay (ELISA).

Results: Renalase levels were significantly lower in the schizophrenia patients than in the control group (p<0.05), whereas DA levels were significantly higher (p<0.05). The epinephrine (Epi) levels of both groups were similar (p=0.186), while the norepinephrine levels in patients with schizophrenia were significantly lower than those in the control group (p<0.05). The areas under the curves for the renalase-dopamine, renalase-norepinephrine and renalase-epinephrine ratios were 0.805, 95% confidence interval (CI): 0.699-0.912 (p<0.001); 0.726, 95% CI: 0.594-0.859 (p=0.032); and 0.656, 95% CI: 0.520-0.791 (p=0.02).

Conclusions: The high DA levels in patients with schizophrenia might be due to low renalase levels. Renalase enzyme levels may play a substantial role in the pathophysiology of schizophrenia. Thus, this enzyme might be a new future target for the treatment and diagnosis of schizophrenia after intrabrain renalase and DA dynamics have been further evaluated.

Uvod: Shizofrenija, posebno oblik sa povećanim dopaminom (DA) je hronični psihijatrijski poremećaj od koga boluju milioni ljudi širom sveta. Relanaza metaboliše supstrate kateholamine (CA), uključujući DA, što ukazuje da može da postoji veza između nivoa relanaze i pojave shizofrenije. Shodno ovome, ovo izučavanje je imalo za cilj da proceni nivoe relanaze i CA u serumu pacijenata sa shizofrenijom.

Metode: Izučavanje je obuhvatilo trideset tri pacijenta sa shizofrenijom i trideset jednu osobu iste starosti i pola kao kontrolnu grupu. Nivoi renalaze i CA mereni su primenom ELISA metode.

Rezultati: Nivoi renalaze bili su značajno niži kod pacijenaza sa shizofrenijom nego u kontrolnoj grupi (p<0,05), dok su nivoi DA bili značajno viši (p<0,05). Nivoi epinefrina (Epi) u obe grupe bili su manji (p=0,186), dok su nivoi norepinfrina u pacijenata sa shizofrenijom bili značajno niži nego u kontrolnoj grupi (p<0,05). Površina ispod krive za renelaze-dopamin i renelaze-epinefrin odnose bili su 0,805, 95% konfidens interval CI: 0,594–0,859 (p=0,032); i 0,656, 95% CI: 0,520–0,791 (p=002).

Zaključak: Visoki nivoi DA u pacijenata sa shizofrenijom mogu biti usled niskih nivoa renalaze. Nivoi renalaze enzima mogu imati značajnu ulogu u patofiziologiji shizofrenije. To znači da ovaj enzima može imati značajnu ulogu u tretmanu i dijagnostikovanju shizofrenije te ona treba dalje da bude izučavana kao i dinamika DA.

Keywords: catecholamine; dopamine; renalase; schizophrenia.