Analysis of the concentrations and size distributions of cell-free DNA in schizophrenia using fluorescence correlation spectroscopy

Abstract

Cell-free DNA (cfDNA), which is primarily released following cell death, has been described and developed to serve as an effective biomarker in autoimmune diseases which may share the pathogenesis with schizophrenia. In this study, we hypothesized and explored whether the concentrations and size distributions of cfDNA are abnormal in schizophrenia. A total of 65 patients with schizophrenia (SZ), 29 patients with mood disorders (MD) and 62 matched healthy controls (HC) were included in the study. Fluorescence correlation spectroscopy was used to assay the molar concentrations and size distributions of cfDNA. Fluorometric quantification and quantitative real-time PCR (qPCR) were performed to verify the results. The cfDNA levels were approximately two-fold higher in the SZ group ((29 ± 15) nM) than in the healthy controls ((15 ± 9) nM; P-value = 0.00062), but the levels in patients with MD were not significantly different from those in the healthy controls ((17 ± 10) nM; P-value = 0.343). According to the size distribution analysis, cfDNA in schizophrenia patients was composed of shorter DNA molecules and showed an apoptosis-like distribution pattern. Our study shows the elevated levels and short sizes of cfDNA in schizophrenia patients, which provide direct evidences supporting increased apoptotic activity in the disease. cfDNA may be developed to serve as an auxiliary diagnostic marker for the disease in the future.

The clinical significance of serum free DNA concentration detection in patients with schizophrenia

“…In this study, we found that patients with schizophrenia had higher levels of cf-DNA in their blood than normal controls. The results of the study are consistent with those of Jiang [29] which testified that apoptosis exists in SZ patients and laid the foundation for the evaluation of clinical treatment effect. Our research is supplemented and expanded on this basis.…”

“…1). SZ patients were divided into undifferentiated type (133), paranoid (11), acute schizophrenia-like psychosis (29), and other subtypes (2). The average concentration of cf-DNA in the different types were respectively 533.5 ng/ml (interquartlie range 237.1-1095.9 ng/ml), 849.9 ng/ml (interquartlie range 450.5-1378.6 ng/ml) and 1115.3 ng/ml (interquartlie range 167.1-1673.4 ng/ml).…”

“…While the fragments greater than 10,000 bp are from necrotic cells [26]. Rencent study suggested that there is a higher concentration of short DNA molecules in the schizophrenia patients [29]. In this study, 115 bp fragments were selected as primers to amplify and calculate its content.…”

“…Serum samples were collected at from 174 patients with schizophrenia (the SZ group) who were from the Nantong Fourth Peoples Hospital, from 1st December 2017 to 1st August 2018. SZ patients were divided into undifferentiated type (133), paranoid (11), acute schizophrenia-like psychosis (29), and other subtypes (2).The diagnosis of schizophrenia was based on the criteria of Diagnostic and…”

“…When the cut-off value was 567.1 ng/ml, the sensitivity was 51.72% and the specificity was 90%, with a 95% confidence interval of 44.04%-59.35%. SZ patients were divided into undifferentiated type (133), paranoid (11), acute schizophrenia-like psychosis (29), and other subtypes (2). Based on the cut-off value of 567.1 ng/ml, there is undifferentiated type 63 (47.7%), the paranoid 8 (72.7%), acute schizophrenia -like psychosis 19 (65.6%), no statistical differences between different classification groups (P > 0.05) (Fig.…”