Metagenome-wide association of gut microbiome features for schizophrenia.

Evidence is mounting that the gut-brain axis plays an important role in mental diseases fueling mechanistic investigations to provide a basis for future targeted interventions. However, shotgun metagenomic data from treatment-naïve patients are scarce hampering comprehensive analyses of the complex interaction between the gut microbiota and the brain. Here we explore the fecal microbiome based on 90 medication-free schizophrenia patients and 81 controls and identify a microbial species classifier distinguishing patients from controls with an area under the receiver operating characteristic curve (AUC) of 0.896, and replicate the microbiome-based disease classifier in 45 patients and 45 controls (AUC = 0.765). Functional potentials associated with schizophrenia include differences in short-chain fatty acids synthesis, tryptophan metabolism, and synthesis/degradation of neurotransmitters. Transplantation of a schizophrenia-enriched bacterium, Streptococcus vestibularis, appear to induces deficits in social behaviors, and alters neurotransmitter levels in peripheral tissues in recipient mice. Our findings provide new leads for further investigations in cohort studies and animal models.

Increased methylation of glucocorticoid receptor gene promoter 1F in peripheral blood of patients with generalized anxiety disorder.

Previous findings on the dysfunction of hypothalamic-pituitary-adrenal (HPA) axis in generalized anxiety disorder (GAD) are controversial, and the molecular mechanisms underlying such dysfunction remain unclear. We analyzed the methylation status of the NR3C1 1F promoter and the expression of glucocorticoid receptor-α isoform (GRα) in peripheral blood mononuclear cells (PMBCs), the basal cortisol level in serum, and a functional neuroendocrine marker for GR sensitivity in the PMBCs in 64 patients with current GAD and 85 healthy controls. We found that patients with GAD had significantly elevated levels of morning basal serum cortisol (P < 0.0001) and diminished GR sensitivity in the PBMCs (P < 0.0001) compared with healthy controls. The overall methylation levels across NR3C1 1F promoter (P < 0.0001) and percent methylation at each of the 5 CpG sites including CpG12, 21, 30, 31, and 32 (P < 0.001) significantly increased. Accordingly, the mRNA levels of GRα significantly decreased (P < 0.0001) in the PBMCs in patients with GAD compared with healthy controls, with the effects specific in patients without childhood traumatic experience. Moreover, both serum basal cortisol levels and GR sensitivity in the PBMCs were negatively correlated with the overall methylation levels of the NR3C1 1F promoter (P < 0.0001) and positively correlated with GRα mRNA levels (P = 0.007) in the PBMCs. In sum, our study revealed the increased activity of the HPA axis and diminished peripheral glucocorticoid responsiveness of GR underlying episodes of GAD. Furthermore, such dysfunction of the HPA axis is associated with both increased DNA methylation of NR3C1 1F promoter and decreased GRα expression.

Repetitive transcranial magnetic stimulation for treating the symptoms of schizophrenia: A PRISMA compliant meta-analysis.

OBJECTIVE: To explore the efficacies of 1-Hz (low frequency) and 10-Hz (high frequency) repetitive transcranial magnetic stimulation (rTMS) in treating auditory hallucinations and negative symptoms of schizophrenia, respectively. METHODS: Electronic databases were searched to identify relevant literature. Standard mean difference (SMD) and 95% confidence interval (CI) values were used to evaluate the effects of rTMS. The stability and sensitivity of the results, the source of heterogeneity, and the recommended grade of the evidence were also analyzed. RESULTS: Thirteen studies of 1-Hz rTMS were included. The auditory hallucinations improved more in the rTMS group than in the sham group (SMD=-0.29, 95%CI=-0.57 to -0.01). However, this result was not stable after sensitivity analysis, and publication bias had a substantial impact on the results. Meta-analysis performed for seven studies of 10-Hz rTMS found that improvement of negative symptoms did not differ significantly between the real rTMS and sham groups. Finally, the grade of evidence for this meta-analysis was found to be low. CONCLUSION: Although there may appear to be a therapeutic effect for 1-Hz rTMS on auditory hallucinations of schizophrenia, this needs to be confirmed by large-scale randomized controlled trials before this finding can be recommended in clinical practice. SIGNIFICANCE: 1-Hz rTMS might have an effect on auditory hallucinations of schizophrenia.

Associations between dopamine D2 receptor gene polymorphisms and schizophrenia risk: a PRISMA compliant meta-analysis.

OBJECTIVE: To determine the relationships between dopamine D2 receptor gene polymorphisms and the risk of schizophrenia using meta-analysis. METHOD: The PubMed, Embase, and China National Knowledge Infrastructure databases were searched to identify relevant literature published up to February 2016. The allele contrast model was used. Stata software was used for statistical analysis, with odds ratios (ORs) and 95% confidence intervals (CIs) calculated to evaluate the associations between dopamine D2 receptor gene polymorphisms and the risk of schizophrenia. Meta-regression and publication bias, trim-and-fill, subgroup, sensitivity, cumulative, and fail-safe number analyses were also performed. RESULTS: This meta-analysis included 81 studies. The rs1801028 and rs1799732 were associated with schizophrenia risk among Asians (P=0.04, OR =1.25, 95% CI =1.01-1.55; P<0.01, OR =0.76, 95% CI =0.63-0.92, respectively), while the rs6277 was associated with schizophrenia risk in Caucasians (P<0.01, OR=0.72, 95% CI =0.66-0.79). The rs1800497 was also associated with schizophrenia risk in population-based controls (P<0.01, OR =0.84, 95% CI =0.72-0.97). The rs6275, rs1079597, and rs1800498 were not associated with schizophrenia risk. In addition, meta-regression indicated that the controls may be sources of heterogeneity for the rs1801028 single-nucleotide polymorphism (SNP), while ethnicity may be sources of heterogeneity for the rs6277 SNP. Publication bias was significant for the rs1801028 SNP, and this result changed after the publication bias was adjusted using the trim-and-fill method. CONCLUSION: This meta-analysis demonstrated that the rs1801028 may be a risk factor for susceptibility to schizophrenia among Asians, while the rs1799732 may be a protective factor for that population. Large-sample studies are necessary to verify the results of this meta-analysis.

[Effects of Temperature on the Preparation of Al/Zn3N2 Thin Films Using Magnetron Reactive Sputtering].

The effects of substrate temperature on the plasma active species were investigated by plasma optical emission spectroscopy. With increasing substrate temperature, the characteristic spectroscopy intensity of the first positive series of N2* (B(3)Πg-->A(3)Σu(+)), the second positive N2* (C(3)Πu-->B(3)Πg), the first negative series N2(+)* (B(2)Σu(+)-->X(2)Σg(+)) and Zn* are increased. Due to the substrate temperature, each ion kinetic energy is increased and the collision ionization intensified in the chamber. That leading to plasma ion density increase. These phenomenons's show that the substrate temperature raises in a certain range was conducive to zinc nitride thin films growth. Zn3N2 thin films were prepared on Al films using ion sources-assisted magnetron sputtering deposition method. The degree of crystalline of the films was examined with X-ray diffraction (XRD). The results show that has a dominant peak located at 34.359° in room temperature, which was corresponding to the (321) plane of cubic anti-bixbyite zinc nitride structure (JCPDS Card No35-0762). When the substrate temperature was 100 °C, in addition to the (321) reflection, more diffraction peaks appeared corresponding to the (222), (400) and (600) planes, which were located at 31.756°, 36.620° and 56.612° respectively. When the substrate temperature was 200 °C, in addition to the (321), (222), (400) and (600) reflection, more new diffraction peaks also appeared corresponding to the (411), (332), (431) and (622) planes, which were located at 39.070, 43.179°, 47.004° and 62.561° respectively. These results show the film crystalline increased gradually with raise the substrate temperature. XP-1 profilometer were used to analyze the thickness of the Zn3N2 films. The Zn3N2 films deposited on Al films in mixture gas plasma had a deposition rate of 2.0, 2.2, and 2.7 nm · min(-1). These results indicate that the deposition rate was gradually enhanced as substrate temperature increased. Field emission scanning electron microscope (SEM) images revealed that the particles of zinc nitride thin films became smaller but more uniform and density with increase the substrate temperature. The Zn3N2 thin films were strongly bound on the Al films. The experiments of films properties analysis results about the substrate temperature were consistent with the results of the plasma optical emission spectroscopy. The results would help improving the preparation of magnetron sputtering technique and getting better Zn3N2 thin films. On the other hand, the results were reflected that the plasma emission spectrum was fast and effective method to analyze the intrinsic characteristics of plasma.