Identification of VIPR2 rare and common variants in the Chinese Han population with schizophrenia

IntroductionSchizophrenia is a severe and chronic psychiatric disorder with hereditary risk up to 80% as previous studies indicated. Several researches have demonstrated a significant association between schizophrenia and microduplications that overlap the vasoactive intestinal peptide receptor 2 gene (VIPR2).MethodsTo further investigate potential causal VIPR2 gene variants, all exons and un-translated portions of the VIPR2 gene were sequenced using amplicon targeted resequencing in 1804 Chinese Han patients with schizophrenia and 996 healthy counterparts in the present study.ResultsNineteen rare non-synonymous mutations and 1 frameshift deletion was identified for schizophrenia, among which 5 variants have never been reported so far. Frequencies of rare non-synonymous mutations were significantly different between the two groups. Specifically, the non-synonymous mutation rs78564798 (Pallele = 0.006) as well as two rare variations in the VIPR2 gene’s introns (rs372544903, Pallele = 0.026 and a novel mutation, chr7:159034078, GRCh38, Pallele = 0.048) were significantly associated with schizophrenia.DiscussionOur findings add new evidence that the functional and probable causative variants of VIPR2 gene may play an important role in susceptibility to schizophrenia. Further studies on validations of VIPR2’s function in the etiology of schizophrenia are warranted

The Shared and Distinct White Matter Networks Between Drug-Naive Patients With Obsessive-Compulsive Disorder and Schizophrenia

Background: Obsessive-compulsive disorder (OCD) and schizophrenia (SZ) as two severe mental disorders share many clinical symptoms, and have a tight association on the psychopathological level. However, the neurobiological substrates between these two diseases remain unclear. To the best of our knowledge, no study has directly compared OCD with SZ from the perspective of white matter (WM) networks.Methods: Graph theory and network-based statistic methods were applied to diffusion MRI to investigate and compare the WM topological characteristics among 29 drug-naive OCDs, 29 drug-naive SZs, and 65 demographically-matched healthy controls (NC).Results: Compared to NCs, OCDs showed the alterations of nodal efficiency and strength in orbitofrontal (OFG) and middle frontal gyrus (MFG), while SZs exhibited widely-distributed abnormalities involving the OFG, MFG, fusiform gyrus, heschl gyrus, calcarine, lingual gyrus, putamen, and thalamus, and most of these regions also showed a significant difference from OCDs. Moreover, SZs had significantly fewer connections in striatum and visual/auditory cortices than OCDs. The right putamen consistently showed significant differences between both disorders on nodal characteristics and structural connectivity.Conclusions: SZ and OCD present different level of anatomical impairment and some distinct topological patterns, and the former has more serious and more widespread disruptions. The significant differences between both disorders are observed in many regions involving the frontal, temporal, occipital, and subcortical regions. Particularly, putamen may serve as a potential imaging marker to distinguish these two disorders and may be the key difference in their pathological changes

Gut microbial DL-endopeptidase alleviates Crohn's disease via the NOD2 pathway

The pattern-recognition receptor NOD2 senses bacterial muropeptides to regulate host immunity and maintain homeostasis. Loss-of-function mutations in NOD2 are associated with Crohn's disease (CD), but how the variations in microbial factors influence NOD2 signaling and host pathology is elusive. We demonstrate that the Firmicutes peptidoglycan remodeling enzyme, DL-endopeptidase, increased the NOD2 ligand level in the gut and impacted colitis outcomes. Metagenomic analyses of global cohorts (n = 857) revealed that DL-endopeptidase gene abundance decreased globally in CD patients and negatively correlated with colitis. Fecal microbiota from CD patients with low DL-endopeptidase activity predisposed mice to colitis. Administering DL-endopeptidase, but not an active site mutant, alleviated colitis via the NOD2 pathway. Therapeutically restoring NOD2 ligands with a DL-endopeptidase-producing Lactobacillus salivarius strain or mifamurtide, a clinical analog of muramyl dipeptide, exerted potent anti-colitis effects. Our study suggests that the depletion of DL-endopeptidase contributes to CD pathogenesis through NOD2 signaling, providing a therapeutically modifiable target

Finite element analysis of different fixation methods of screws on absorbable plate for rib fractures

Multiple rib fractures caused by trauma are common injuries and the internal fixation methods of these injuries have been paid more and more attention by surgeons. Absorbable plates and screws are the effective way to treat rib fractures, but there are no reports on which type of screw fixation method is most effective. In this study, finite element analysis was used to study the effects of five different types of screw fixation methods on anterior rib, lateral rib and posterior rib. The finite element model of the ribs was reconstructed from CT images, and the internal pressure (40 kPa) and intercostal force (30 N) on the surfaces of the ribs were simulated accordingly. An intercostal force of 30 N was applied to the upper and lower surfaces of the ribs to simulate the effect of intercostal muscle force. The pressure of 40 kPa was applied to the inner surface of the ribs, and the normal direction was applied to the inner surface of the ribs. The positive direction was considered inspiratory pressure, and the negative direction was considered expiratory pressure. The results indicate the optimal type of screw fixation on the absorbable plate for rib fractures, and provide a basis and reference for clinical application

Impairment of Working Memory, Decision-making, and Executive Function in the First-Degree Relatives of People with Panic Disorder: A Pilot Study

BackgroundPanic disorder (PD) patients present impairments of working memory, decision-making, and executive function. However, whether the first-degree relatives (FDRs) of people with PD present abnormal characteristics, including clinical and neuropsychological aspects, in comparison to the general population, has not been studied. Investigation and understanding of the abnormal neuropsychological characteristics of the FDRs of people with PD will contribute to the prevention and treatment of PD.ObjectiveThe purpose of this paper is to compare the working memory, decision-making, and executive function among people with PD, their FDRs, and controls.Materials and methodsNeuropsychological functions of 30 people with PD, 30 FDRs of people with PD, and 30 controls were measured with a digit span task, Iowa Gambling Task (IGT), and Wisconsin Card Sorting Test (WCST).ResultsPerseverative errors, failure to maintain set scores, and number of cards chosen from decks A, B, C, and D were higher for People with PD and their FDRs than those of controls. Furthermore, error rates for these tests were higher for people with PD than their FDRs. Forward scores and backward scores, percentage of conceptual level responses, the number of categories completed, choices from advantageous minus disadvantageous decks, and mean amount of money earned of people with PD and their FDRs were all lower than those of controls. Scores for these tests were also lower for people with PD than for their FDRs.ConclusionPeople with PD as well as their FDRs present different degrees of impairments of working memory, decision-making, and executive function. Impaired performance on three tasks appears to be associated with the diathesis for PD and may be a valuable indicator of susceptibility for this disorder

Increased Insular Cortical Thickness Associated With Symptom Severity in Male Youths With Internet Gaming Disorder: A Surface-Based Morphometric Study

With the rising increase in Internet-usage, Internet gaming disorder (IGD) has gained massive attention worldwide. However, detailed cerebral morphological changes remain unclear in youths with IGD. In the current study, our aim was to investigate cortical morphology and further explore the relationship between the cortical morphology and symptom severity in male youths with IGD. Forty-eight male youths with IGD and 32 age- and education-matched normal controls received magnetic resonance imaging scans. We employed a recently proposed surface-based morphometric approach for the measurement of cortical thickness (CT). We found that youths with IGD showed increased CT in the bilateral insulae and the right inferior temporal gyrus. Moreover, significantly decreased CT were found in several brain areas in youths with IGD, including the bilateral banks of the superior temporal sulci, the right inferior parietal cortex, the right precuneus, the right precentral gyrus, and the left middle temporal gyrus. Additionally, youths with IGD demonstrated a significantly positive correlation between the left insular CT and symptom severity. Our data provide evidence for the finding of abnormal CT in distributed cerebral areas and support the notion that altered structural abnormalities observed in substance addiction are also manifested in IGD. Such information extends current knowledge about IGD-related brain reorganization and could help future efforts in identifying the role of insula in the disorder

Cognitive Biases toward Internet Game-Related Pictures and Executive Deficits in Individuals with an Internet Game Addiction

<div><h3>Background</h3><p>The cue-related go/no-go switching task provides an experimental approach to study individual’s flexibility in changing situations. Because Internet addiction disorder (IAD) belongs to the compulsive-impulsive spectrum of disorders, it should present cognitive bias and executive functioning deficit characteristics of some of these types of disorders. Until now, no studies have been reported on cognitive bias and executive function involving mental flexibility and response inhibition in IAD.</p> <h3>Methodology/Principal Findings</h3><p>A total of 46 subjects who met the criteria of the modified Young’s Diagnostic Questionnaire for Internet addiction (YDQ) were recruited as an Internet game addiction (IGA) group, along with 46 healthy control individuals. All participants performed the Internet game-shifting task. Using hit rate, RT, <em>d′</em> and C as the dependent measures, a three-way ANOVA (group × target × condition) was performed. For hit rate, a significant effect of group, type of target and condition were found. The group–target interaction effect was significant. For RT, significant effects were revealed for group and type of target. The group–target interaction effect was significant. Comparisons of the means revealed that the slowing down of IGA relative to NIA was more pronounced when the target stimuli were neutral as opposed to Internet game-related pictures. In addition, the group–condition interaction effect was significant. For <em>d′</em>, significant effects of group, type of target and condition were found. The group–target interaction effect was significant. For C, the type of target produced a significant effect. There was a positive correlation between the length of the addiction (number of years) and the severity of the cognitive bias.</p> <h3>Conclusions</h3><p>IGA present cognitive biases towards information related to Internet gaming. These biases, as well as poor executive functioning skills (lower mental flexibility and response inhibition), might be responsible for Internet game addiction. The assessment of cognitive biases in IGA might provide a methodology for evaluation of therapeutic effects.</p> </div