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.

Housekeeping proteins are essential endogenous controls for normalization as they are expected to be stably expressed. However, the stability of the expression level of housekeeping proteins needs to be assessed considering various experimental conditions. Our study evaluated the degree of variability of 7 commonly used housekeeping proteins with regard to their potential utility as normalizers in 56 pairs of matched colorectal adenocarcinoma (CRC) tissue samples and 6 pairs of hepatocellular carcinoma (HCC) tissue samples using multiple reaction monitoring (MRM) and Western blot analyses. A comprehensive experimental design and strict statistical analysis revealed that the expression levels of these 7 housekeeping proteins were not as stable as expected and they all exhibited upregulations to varying degrees in both the CRC and the HCC tissue samples. Consequently, we verified that using the amount of total protein instead of that of an individual protein can serve as a preferable control for studies of protein expression that require normalization.

Schizophrenia is a debilitating mental disorder and often has a prodromal period, referred to as clinical high risk (CHR) for psychosis, prior to the first episode. The etiology and pathogenesis of schizophrenia remain unclear. Despite the human gut microbiome being associated with schizophrenia, the role of the oral microbiome, which is a vital player in the mouth–body connection, is not well understood. To address this, we performed 16S rRNA gene sequencing to investigate the salivary microbiome in 85 patients with drug-naïve first-episode schizophrenia (FES), 43 individuals at CHR, and 80 healthy controls (HCs). The salivary microbiome of FES patients was characterized by higher α-diversity and lower β-diversity heterogeneity than those of CHR subjects and HCs. Proteobacteria, the predominant phylum, was depleted, while Firmicutes and the Firmicutes/Proteobacteria ratio was enriched, in a stepwise manner from HC to CHR to FES. H2S-producing bacteria exhibited disease-stage-specific enrichment and could be potential diagnostic biomarkers for FES and CHR. Certain salivary microbiota exhibited disease-specific correlation patterns with symptomatic severities, peripheral pro-inflammatory cytokines, thioredoxin, and S100B in FES. Furthermore, the metabolic functions from inferred metagenomes of the salivary microbiome were disrupted in FES, especially amino acid metabolism, carbohydrate metabolism, and xenobiotic degradation. This study has established a link between salivary microbiome alterations and disease initiation and provided the hypothesis of how the oral microbiota could influence schizophrenia.

Previous studies have indicated that schizophrenia is linked to abnormal lipid metabolism. Free fatty acids (FFAs) in peripheral blood can reflect the status of lipid metabolism in human body. The purpose of this study was to scan the FFA pattern and elucidate the characteristics of lipid metabolic abnormality in schizophrenia patients. One hundred and ten patients with schizophrenia (SCZs) and 109 healthy controls (HCs) were included in the study and divided into a discovery set and a validation set. Forty-seven serum FFAs were detected by UPLC-QTOF-MS and 39 of them were absolutely quantified by establishing standard curves. Monounsaturated fatty acids (MUFAs) and ω-6 polyunsaturated fatty acids (ω-6 PUFAs) were significantly increased in SCZs compared with HCs. Desaturation from saturated fatty acids to MUFAs and β-oxidation were enhanced, as estimated by the ratios of products to precursors. These results suggest that lipolysis and β-oxidation are upregulated in SCZ, presumably resulting from insufficient brain energy supply.