Increased Ribosome Biogenesis and Increased Oxidative Stress in Blood Leukocytes of Patients With Catatonic Schizophrenia Compared With Paranoid Schizophrenia.

Abstract

Background: Schizophrenia (SZ) is associated with chronic oxidative stress in the patient's body. Previous studies revealed an increased copy number of genes for 47S pre-ribosomal RNA (pre-rRNA) in SZ patients. In this study, levels of oxidative stress and factors involved in the adaptive response to chronic stress (rDNA transcription) were, for the first time, compared in blood cells of patients with catatonic SZ(C) and paranoid SZ(P), chronic forms of schizophrenia, as well as healthy controls (HC).

Methods: Ribosomal DNA (rDNA) and telomere repeat (TR) were quantified in leukocyte DNA using non-radioactive quantitative hybridization. Fragments of 5' external transcribed spacer (5' ETS) and 18S rRNA were assayed in leukocyte RNA using quantitative reverse transcription PCR (RT-qPCR). Proteins γ-histone H2AX (γH2AX), NADPH-oxidase 4 (NOX4), nuclear factor erythroid 2-related factor 2 (NRF2), BCL2-like protein 4 (BAX), BCL2, and oxidation marker 8-oxo-2'-deoxyguanosine (8-oxodG) were quantified in blood lymphocytes using flow cytometry.

Results: SZ(C) cells exhibited higher levels of the oxidative stress markers than SZ(P) and HC cells. The rDNA copy numbers in SZ(C) genomes negatively correlated with the amounts of the oxidative stress markers levels. Thus, genomes of blood cells isolated from catatonic patients harbor more copies of ribosomal genes than those from paranoid schizophrenia patients, correlating with higher levels of rRNA in catatonic patients.

Conclusions: The upregulated ribosome biogenesis appears to be required for adaptive response to the elevated levels of oxidative stress in catatonic compared to paranoid patients.