Epigenetic alterations represent a sort of functional modifications related to the genome that are not responsible for changes in the nucleotide sequence. DNA methylation is one of such epigenetic modifications that have been studied intensively for the past several decades. The transfer of a methyl group to the 5 position of a cytosine is the key feature of DNA methylation. A simple change as such can be caused by a variety of factors, which can be the cause of many serious diseases including several neurodegenerative diseases. In this review, we have reviewed and summarized recent progress regarding DNA methylation in four major neurodegenerative diseases: Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). The studies of these four major neurodegenerative diseases conclude the strong suggestion of the important role DNA methylation plays in these diseases. However, each of these diseases has not yet been understood completely as details in some areas remain unclear, and will be investigated in future studies. We hope this review can provide new insights into the understanding of neurodegenerative diseases from the epigenetic perspective.

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Background: There is a crucial link between the gut microbiota and the host central nervous system, and the communication between them occurs via a bidirectional pathway termed the “microbiota-gut-brain axis.” The gut microbiome in the modern environment has markedly changed in response to environmental factors. These changes may affect a broad range of host psychiatric disorders, such as depression, by interacting with the host through metabolic, immune, neural, and endocrine pathways. Nevertheless, the general aspects of the links between the gut microbiota and depression have not been systematically investigated through bibliometric analysis.Aim: This study aimed to analyze the current status and developing trends in gut microbiota research in the depression field through bibliometric and visual analysis.Methods: A total of 1,962 publications published between 1999 and 2019 were retrieved from the Web of Science Core Collection. CiteSpace (5.6 R5) was used to perform collaboration network analysis, co-citation analysis, co-occurrence analysis, and citation burst detection.Results: The number of publications has been rapidly growing since 2010. The collaboration network analysis revealed that the USA, University College Cork, and John F. Cryan were the most influential country, institute, and scholar, respectively. The most productive and co-cited journals were Brain Behavior and Immunity and Proceedings of the National Academy of Sciences of the United States of America, respectively. The co-citation analysis of references revealed that the most recent research focus was in the largest theme cluster, “cytokines,” thus reflecting the important research foundation in this field. The co-occurrence analysis of keywords revealed that “fecal microbiota” and “microbiome” have become the top two research hotspots since 2013. The citation burst detection for keywords identified several keywords, including “Parkinson's disease,” “microbiota-gut-brain axis,” “microbiome,” “dysbiosis,” “bipolar disorder,” “impact,” “C reactive protein,” and “immune system,” as new research frontiers, which have currently ongoing bursts.Conclusions: These results provide an instructive perspective on the current research and future directions in the study of the links between the gut microbiota and depression, which may help researchers choose suitable cooperators or journals, and promote their research illustrating the underlying molecular mechanisms of depression, including its etiology, prevention, and treatment.

The kynurenine pathway, in which tryptophan is metabolized to kynurenine and kynurenic acid, has been linked to depression. A rapid and highly reproducible liquid-chromatography-tandem mass spectrometry (LC-MS/MS) method were established for determining tryptophan, kynurenine and kynurenic acid in human serum. Biological samples were precipitated with methanol before separation on an Agilent Eclipse XDB-C18. The stable-isotope-labeled internal standards (kynurenine-CN and kynurenic acid-d) were used for quantification. Detection was performed using multiple reaction monitoring in electrospray ionization mode at m/z 205.1→188.1 for tryptophan, m/z 209.1→146.1 for kynurenine, m/z 190.1→144.1 for kynurenic acid. Good linearity of analyte to internal standard peak area ratios was seen in the concentration range 1,000-50,000 ng/mL for tryptophan, 100-5,000 ng/mL for kynurenine and 1-60 ng/mL for kynurenic acid. Pooled drug-free human serum was purified using activated charcoal and the method was shown to be linear, with validation parameters within acceptable limits. The newly developed method was successfully used to determine concentrations of tryptophan, kynurenine and kynurenic acid in serum from 26 healthy volunteers and 54 patients with depression. Concentrations of tryptophan and kynurenine were lower in serum from depressed individuals than from healthy individuals.

Background: The objective of this study was to investigate the serum concentrations of olanzapine in relation to age, sex, and other factors in Chinese patients aged between 10 and 90 years. Methods: Data for 884 olanzapine patients, deposited between 2016 and 2017, were retrieved from the therapeutic drug monitoring database of the Affiliated Brain Hospital of Guangzhou Medical University. The effects of covariates on serum olanzapine concentration, dose-normalized concentration (C/D ratio), and normalized concentration (C/D/weight) were investigated. Results: Generally, male patients had lower olanzapine concentration, C/D ratio, and C/D/weight than female patients (P < 0.001). Smoking and drinking reduced olanzapine concentration, C/D ratio, and C/D/weight (P < 0.001). Coadministration with valproate decreased olanzapine concentration, C/D ratio, and C/D/weight by about 16%, 30%, and 40%, respectively (P < 0.001). Patients younger than 60 years had higher olanzapine concentrations (P < 0.05) but lower C/D ratios and C/D/weight (P < 0.001) than patients older than 60 years. Age was correlated with olanzapine concentration (r = −0.082, P < 0.05), C/D ratio (r = 0.196, P < 0.001), and C/D/weight (r = 0.169, P < 0.001). Sample timing after dose and diagnostic factors also contributed to the olanzapine concentrations. Multiple linear regression analysis revealed significant influences of dosage, age, sex, valproate comedication, smoking, postdose interval, and schizophrenia (vs bipolar affective disorders) on serum olanzapine concentrations. Conclusions: The metabolism of olanzapine may be altered by several factors. Patients characterized with a combination of factors may benefit from therapeutic drug monitoring for the adjustment of olanzapine dose to minimize adverse reactions.

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