RAB18, a protein associated with Warburg Micro syndrome, controls neuronal migration in the developing cerebral cortex

There is no apparently changed after overexpression of RAB18 in cortical neuronal migration. A Representative coronal section showing migration of transfected neurons 4 d after electroporated at E14.5 with GFP plasmid together with indicated constructs. Scale bar: 100 μm. B Quantitative analysis of GFP positive neurons in different cortical regions in A. Data represent the mean ± SEM (n = 3). (PDF 76 kb

Evidence for association between Disrupted-in-schizophrenia 1 (DISC1) gene polymorphisms and autism in Chinese Han population: a family-based association study

<p>Abstract</p> <p>Background</p> <p>Disrupted-in-Schizophrenia 1 (<it>DISC1</it>) gene is one of the most promising candidate genes for major mental disorders. In a previous study, a Finnish group demonstrated that <it>DISC1 </it>polymorphisms were associated with autism and Asperger syndrome. However, the results were not replicated in Korean population. To determine whether <it>DISC1 </it>is associated with autism in Chinese Han population, we performed a family-based association study between <it>DISC1 </it>polymorphisms and autism.</p> <p>Methods</p> <p>We genotyped seven tag single nucleotide polymorphisms (SNPs) in <it>DISC1</it>, spanning 338 kb, in 367 autism trios (singleton and their biological parents) including 1,101 individuals. Single SNP association and haplotype association analysis were performed using the family-based association test (FBAT) and Haploview software.</p> <p>Results</p> <p>We found three SNPs showed significant associations with autism (rs4366301: G > C, Z = 2.872, <it>p </it>= 0.004; rs11585959: T > C, Z = 2.199, <it>p </it>= 0.028; rs6668845: A > G, Z = 2.326, <it>p </it>= 0.02). After the Bonferroni correction, SNP rs4366301, which located in the first intron of <it>DISC1</it>, remained significant. When haplotype were constructed with two-markers, three haplotypes displayed significant association with autism. These results were still significant after using the permutation method to obtain empirical <it>p </it>values.</p> <p>Conclusions</p> <p>Our study provided evidence that the <it>DISC1 </it>may be the susceptibility gene of autism. It suggested <it>DISC1 </it>might play a role in the pathogenesis of autism.</p

Existence of One-Signed Solutions of Discrete Second-Order Periodic Boundary Value Problems

We prove the existence of one-signed periodic solutions of second-order nonlinear difference equation on a finite discrete segment with periodic boundary conditions by combining some properties of Green's function with the fixed-point theorem in cones

Comparison of the probability of four anticonvulsant mood stabilizers to facilitate polycystic ovary syndrome in women with epilepsies or bipolar disorder—A systematic review and meta-analysis

BackgroundPatients treated with anticonvulsant mood stabilizers have a higher incidence of polycystic ovary syndrome (PCOS). However, there is no comparison between different anticonvulsant mood stabilizers. The purpose of this study was to systematically evaluate the prevalence of PCOS in women taking anticonvulsant mood stabilizers and compare the probability of PCOS caused by different anticonvulsant mood stabilizers.MethodsFive databases, namely PubMed, Embase, Web of Science, Cochrane Library, and Clinical Trials, were searched for literature on anticonvulsant mood stabilizers and PCOS published up to October 28, 2022. This meta-analysis was performed using Revman 5.4, Stata 14.0, and R4.1.0, and effect size pooling was performed in fixed- or random-effects models based on the results of I2 and Q-test, and the surface under the cumulative ranking curve (SUCRA) was used for analysis to assess the cumulative probability of drug-induced PCOS. Publication bias was assessed by funnel plot Egger's test and meta regression.ResultsTwenty studies with a total of 1,524 patients were included in a single-arm analysis, which showed a combined effect size (95% CI) of 0.21 (0.15–0.28) for PCOS in patients taking anticonvulsant mood stabilizers. Nine controlled studies, including 500 patients taking medication and 457 healthy controls, were included in a meta-analysis, which showed OR = 3.23 and 95% CI = 2.19–4.76 for PCOS in women taking anticonvulsant mood stabilizers. Sixteen studies with a total of 1416 patients were included in a network meta-analysis involving four drugs, valproate (VPA), carbamazepine (CBZ), oxcarbazepine (OXC), and lamotrigine (LTG), and the results of the network meta-analysis showed that VPA (OR = 6.86, 95% CI = 2.92–24.07), CBZ (OR = 3.28, 95% CI = 0.99–12.64), OXC (OR = 4.30, 95% CI = 0.40–49.49), and LTG (OR = 1.99, 95% CI = 0.16–10.30), with cumulative probabilities ranked as VPA (90.1%), OXC (63.9%), CBZ (50.1%), and LTG (44.0%).ConclusionThe incidence of PCOS was higher in female patients treated with anticonvulsant mood stabilizers than in the healthy population, with VPA having the highest likelihood of causing PCOS. The most recommended medication when considering PCOS factors is LTG.Systematic review registrationidentifier: CRD4202238092

Association between NAT2 polymorphisms and the risk of schizophrenia in a Northern Chinese Han population

The gene that encodes N-acetyltransferase 2 (NAT2), an enzyme that plays a crucial role in the metabolism of many drugs and xenobiotics, is located on chromosome 8p22, one of the most convictive susceptibility loci of schizophrenia. NAT2 genetic polymorphisms lead to various enzyme acetylation phenotypes. In the present study, six selected NAT2 exonic single nucleotide polymorphisms were genotyped in an independent case-control sample of a Northern Chinese Han population to verify the possible association between NAT2 and schizophrenia. Three (rs1801280T/341C, rs1799930/G590A, and rs1208/A803G) of the six single nucleotide polymorphisms showed significant allele frequency differences between the case and the control groups after rigorous Bonferroni correction. One protective fast-acetylation haplotype (NAT2*4) and two risk slow acetylation haplotypes (NAT2*5B and NAT2*6A) were discovered to be associated with schizophrenia. Our results indicate that NAT2 may be a susceptibility gene for schizophrenia in this Chinese Han population, and the risk haplotypes might cause the impairment of NAT2 in metabolizing neurotoxic substances. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved

Tcf4 controls neuronal migration of the cerebral cortex through regulation of Bmp7

AbstractBackground: Transcription factor 4 (TCF4) is found to be associated with schizophrenia. TCF4 mutations also cause Pitt-Hopkins Syndrome, a neurodevelopmental disorder associated with severe mental retardation. However, the function of TCF4 during brain development remains unclear. Results: Here, we report that Tcf4 is expressed in the developing cerebral cortex. In utero suppression of Tcf4 arrested neuronal migration, leading to accumulation of ectopic neurons in the intermediate zone. Knockdown of Tcf4 impaired leading process formation. Furthermore, Bone Morphogenetic Protein 7 (Bmp7) is upregulated in Tcf4-deficient neurons. In vivo gain of function and rescue experiments demonstrated that Bmp7 is the major downstream effector of Tcf4 required for neuronal migration. Conclusion: Thus, we have uncovered a new Tcf4/Bmp7-dependent mechanism underlying neuronal migration, and provide insights into the pathogenesis of neurodevelopmental disorders

Phosphodiesterase and psychiatric disorders: a two-sample Mendelian randomization study

Abstract Background Phosphodiesterases (PDEs) have been associated with psychiatric disorders in observational studies; however, the causality of associations remains unestablished. Methods Specifically, cyclic nucleotide PDEs were collected from genome-wide association studies (GWASs), including PDEs obtained by hydrolyzing both cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) (PDE1A, PDE2A, and PDE3A), specific to cGMP (PDE5A, PDE6D, and PDE9A) and cAMP (PDE4D and PDE7A). We performed a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the relationship between PDEs and nine psychiatric disorders. The inverse-variance-weighted (IVW) method, MR-Egger, and weighted median were used to estimate causal effects. The Cochran’s Q test, MR-Egger intercept test, MR Steiger test, leave-one-out analyses, funnel plot, and MR pleiotropy residual sum and outlier (MR-PRESSO) were used for sensitivity analyses. Results The PDEs specific to cAMP were associated with higher-odds psychiatric disorders. For example, PDE4D and schizophrenia (SCZ) (odds ratios (OR) = 1.0531, P IVW = 0.0414), as well as major depressive disorder (MDD) (OR = 1.0329, P IVW = 0.0011). Similarly, PDE7A was associated with higher odds of attention-deficit/hyperactivity disorder (ADHD) (OR = 1.0861, P IVW = 0.0038). Exploring specific PDE subtypes and increase intracellular cAMP levels can inform the development of targeted interventions. We also observed PDEs (which hydrolyzes both cAMP and cGMP) was associated with psychiatric disorders [OR of PDE1A was 1.0836 for autism spectrum disorder; OR of PDE2A was 0.8968 for Tourette syndrome (TS) and 0.9449 for SCZ; and OR of PDE3A was 0.9796 for MDD; P < 0.05]. Furthermore, psychiatric disorders also had some causal effects on PDEs [obsessive–compulsive disorder on increased PDE6D and decreased PDE2A and PDE4D; anorexia nervosa on decreased PDE9A]. The results of MR were found to be robust using multiple sensitivity analysis. Conclusions In this study, potential causal relationships between plasma PDE proteins and psychiatric disorders were established. Exploring other PDE subtypes not included in this study could provide a more comprehensive understanding of the role of PDEs in psychiatric disorders. The development of specific medications targeting PDE subtypes may be a promising therapeutic approach for treating psychiatric disorders