UPLC-MS/MS determination of 71 neuropsychotropic drugs in human serum.

In this study, a UPLC-MS/MS method was developed for the rapid detection of 71 neuropsychotropic drugs in human serum for drug concentration monitoring and toxicity screening. The analytes were separated from the biological matrix by protein precipitation using a methanol-acetonitrile solvent mixture. The chromatographic separation was performed on a Kromasil ClassicShell C18 column (2.1*50 mm, 2.5 µ m) with gradient elution using acetonitrile-0.2 % acetic acid and 10 mM ammonium acetate as the mobile phases (flow rate 0.4 mL/min, column temperature 40 °C, injection volume 5 µL). An electrospray ion source in both positive and negative ion modes with multiple ion monitoring was used. The total run time was 6 min. All compounds were quantified using the isotope internal standard method. Totally, 71 drugs were detected within their linear ranges with correlation coefficients greater than 0.990. The intra- and inter-batch precision relative standard deviations (RSDs) for the low, medium, and high concentration points were less than 15 %, with an accuracy of 90%-110 %. All compounds except Moclobemide N-oxindole are stabilised within 7 days. The relative matrix effect results for each analyte were within ±20 % of the requirements. The method is validated according to Clinical and Laboratory Standards Institute guidelines, easy to use, and has a low cost.

Dysbiosis of the Gut Microbiota and Kynurenine (Kyn) Pathway Activity as Potential Biomarkers in Patients with Major Depressive Disorder.

With increasing attention paid to the concept of the microbiota-gut-brain axis, mounting evidence reveals that the gut microbiota is involved in a variety of neurological and psychiatric diseases. However, gut microbiota changes in major depressive disorder (MDD) patients and their association with disease mechanisms remain undefined. Fifty MDD patients and sixty healthy controls were recruited from the Shanghai Healthy Mental Center, China. Fecal samples were collected, and the compositional characteristics of the intestinal flora were determined in MDD patients by MiSeq sequencing. Venous blood was collected for the detection of plasma indoleamine-2,3-dioxygenase (Ido), kynurenine (Kyn) and tryptophan (Trp) levels. Stool samples of bacterial 16S sequencing was carried out. A total of 2,705,809 optimized sequences were obtained, with an average of 54,116 per sample. More unique OTUs were observed at the family, genus and species levels in the control group compared with the MDD cases. Further analysis showed significant changes in the α- and ß-diversities and relative abundance levels of gut microbial entities in MDD patients, as well as elevated amounts of Ido and Kyn indicating Kyn pathway activation, KEGG bacterial 16S function prediction analysis shows a variety of amino acids and metabolic (including Ido, Trp and Kyn) changes in the body of patients with MDD. These may result in increased neurotoxic metabolites and reduced generation of serotonin in the disease process. These changed factors may potentially be utilized as biomarkers for MDD in the future, playing more important roles in the disease course.

Consensus on potential biomarkers developed for use in clinical tests for schizophrenia.

Background: Schizophrenia is a serious mental illness affecting approximately 20 million individuals globally. Both genetic and environmental factors contribute to the illness. If left undiagnosed and untreated, schizophrenia results in impaired social function, repeated hospital admissions, reduced quality of life and decreased life expectancy. Clinical diagnosis largely relies on subjective evidence, including self-reported experiences, and reported behavioural abnormalities followed by psychiatric evaluation. In addition, psychoses may occur along with other conditions, and the symptoms are often episodic and transient, posing a significant challenge to the precision of diagnosis. Therefore, objective, specific tests using biomarkers are urgently needed for differential diagnosis of schizophrenia in clinical practice. Aims: We aimed to provide evidence-based and consensus-based recommendations, with a summary of laboratory measurements that could potentially be used as biomarkers for schizophrenia, and to discuss directions for future research. Methods: We searched publications within the last 10 years with the following keywords: 'schizophrenia', 'gene', 'inflammation', 'neurotransmitter', 'protein marker', 'gut microbiota', 'pharmacogenomics' and 'biomarker'. A draft of the consensus was discussed and agreed on by all authors at a round table session. Results: We summarised the characteristics of candidate diagnostic markers for schizophrenia, including genetic, inflammatory, neurotransmitter, peripheral protein, pharmacogenomic and gut microbiota markers. We also proposed a novel laboratory process for diagnosing schizophrenia in clinical practice based on the evidence summarised in this paper. Conclusions: Further efforts are needed to identify schizophrenia-specific genetic and epigenetic markers for precise diagnosis, differential diagnosis and ethnicity-specific markers for the Chinese population. The development of novel laboratory techniques is making it possible to use these biomarkers clinically to diagnose disease.

Research Progress on the Correlation Between Epigenetics and Schizophrenia.

PURPOSE OF THE REVIEW: Nowadays, the incidence of schizophrenia is noticeably increased. If left undiagnosed and untreated, it will lead to impaired social functions, repeated hospital admissions, decline in quality of life and life expectancy. However, the diagnosis of schizophrenia is complicated and challenging. Both genetic and environmental factors are considered as important contributors to the development and progression of this disorder. The environmental factors have been linked to changes in gene expression through epigenetic modulations, which have raised more and more research interests in recent years. This review article is to summarize the current findings and understanding of epigenetic modulation associated with pathogenesis of schizophrenia, aiming to provide useful information for further research in developing biomarkers for schizophrenia. RECENT FINDINGS: Three major types of epigenetic modulations have been described in this article. Firstly, both DNA hypermethylation and hypomethylated have been associated with schizophrenia via analyzing post-mortem brain tissues and peripheral blood of patients. Specific changes of non-coding RNAs, particularly microRNAs and long-chain non-coding RNAs, have been observed in central and peripheral samples of schizophrenia patients, indicating their significant diagnostic value for the disease, and may also potentially predict treatment response. The correlation between histone modification and schizophrenia, however, is largely unclear. SUMMARY: Epigenetic modulations, including DNA methylation, ncRNA transcriptional regulation and histone modification, play an important role in the pathogenesis of schizophrenia. Therefore, tests of these epigenetic alterations may be utilized to assist in the diagnosis and determination of strategies of individualized treatment in clinical practice.