NRF2 and HMOX1 Gene Expression against the Background of Systemic Oxidative Stress in Patients with Acute Psychosis

The aim of this study was to evaluate NRF2 and HMOX1 gene expression against the background of systemic oxidative stress in patients with acute psychosis. The study included 40 patients with newly developed paranoid schizophrenia, 22 subjects with new-onset acute psychosis associated with excessive alcohol consumption, and 25 healthy volunteers. The signs of systemic oxidative stress were assessed by 8-dihydro-2'-deoxyguanosine (8-oxodG) contents in peripheral blood lymphocytes (PBL) and in cell-free (cf) DNA samples obtained from plasma specimens of the patients and healthy controls. The patients of both groups demonstrated a significant (a hundredfold) increase in 8-oxodG content in cfDNA samples and a marked (5- to 8-fold) elevation of 8-oxodG concentration in PBL. Against the background of systemic oxidative stress, there was a statistically significant increase in NRF2 protein expression as well as marked elevation of NRF2 and Hmox1 gene transcriptional activity in PBL obtained from alcoholic patients. In contrast, the subjects with newly developed paranoid schizophrenia demonstrated decrease in expression of NRF2, the master regulator of anti-oxidant defenses, as well as reduction of NRF-2 and Hmox1 gene transcriptional activity compared to both healthy controls and alcoholic patients. In conclusion, against the background of systemic oxidative stress associated acute psychosis development, PBL of patients with paranoid schizophrenia was characterized by reduced NRF2 gene transcriptional activity and decreased NRF2 protein expression.