Identification of Immune-Related Gene Signature in Schizophrenia.

BACKGROUND: Schizophrenia (SCZ) is a type of psychiatric disorder characterized by multiple symptoms. Our aim is to decipher the relevant mechanisms of immune-related gene signatures in SCZ. METHODS: The SCZ dataset and its associated immunoregulatory genes were retrieved using Gene Expression Omnibus (GEO) and single-sample gene set enrichment analysis (ssGSEA). Co-expressed gene modules were determined through weighted gene correlation network analysis (WGCNA). To elucidate the functional characteristics of these clusters, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used. Additionally, gene set enrichment analysis (GSEA) and Gene Set Variation Analysis (GSVA) were conducted to identify enriched pathways for the immune subgroups. A protein-protein interaction (PPI) network analysis was performed to identify core genes relevant to SCZ. RESULTS: A significantly higher immune score was observed in SCZ compared to control samples. Seven distinct gene modules were identified, with genes highlighted in green selected for further analysis. Using the Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) method, degrees of immune cell adhesion and accumulation related to 22 different immune cell types were calculated. Significantly enriched bioprocesses concerning the immunoregulatory genes with differential expressions included interferon-beta, IgG binding, and response to interferon-gamma, according to GO and KEGG analyses. Eleven hub genes related to immune infiltration emerged as key players among the three top-ranked GO terms. CONCLUSIONS: This study underscores the involvement of immunoregulatory reactions in SCZ development. Eleven immune-related genes (IFITM1 (interferon induced transmembrane protein 1), GBP1 (guanylate binding protein 1), BST2 (bone marrow stromal cell antigen 2), IFITM3 (interferon induced transmembrane protein 3), GBP2 (guanylate binding protein 2), CD44 (CD44 molecule), FCER1G (Fc epsilon receptor Ig), HLA-DRA (major histocompatibility complex, class II, DR alpha), FCGR2A (Fc gamma receptor IIa), IFI16 (interferon gamma inducible protein 16), and FCGR3B (Fc gamma receptor IIIb)) were identified as hub genes, representing potential biomarkers and therapeutic targets associated with the immune response in SCZ patients.

Mediating role of impaired wisdom in the relation between childhood trauma and psychotic-like experiences in Chinese college students: a nationwide cross-sectional study.

BACKGROUND: The association between childhood trauma (CT) and psychotic-like experiences (PLEs) is well-established. Many previous studies have recognized wisdom as a protective factor for mental health, but its role in the relation between CT and PLEs remains unknown. We aimed to investigate the mediating effect of wisdom in the above association among Chinese college students. METHODS: We conducted a nationwide survey covering 9 colleges across China and recruited a total of 5873 students using online questionnaires between September 14 and October 18, 2021. Convenience sampling was adopted. We employed the San Diego Wisdom Scale (SD-WISE), the Childhood Trauma Questionnaire (CTQ-28), and the 15-item Positive Subscale of the Community Assessment of Psychic Experiences (CAPE-15) to measure the wisdom, CT and PLEs, respectively. Descriptive, correlation, and mediation analysis were utilized. RESULTS: The positive correlation between CT and PLEs was well-replicated among college students (Pearson's r = 0.30, p < 0.001). Wisdom was negatively associated with CT (Pearson's r = - 0.46, p < 0.001) and frequency of PLEs (Pearson's r = - 0.25, p < 0.001). Total wisdom scores partially mediated the relationship between cumulative childhood trauma, neglect, abuse and PLEs, separately. The mediated model respectively explained 21.9%, 42.54% and 18.27% of the effect of CT on PLEs. Our model further suggested that childhood trauma could be related to PLEs through decreasing the following wisdom components: decisiveness, emotional regulation and prosocial behavior. CONCLUSION: For the first time, our results suggested that impaired wisdom played a role in the translation from childhood adversity to subclinical psychotic symptoms, implicating wisdom as a possible target for early intervention for psychosis among young individuals. Longitudinal work is warranted to verify the clinical implications.

Altered resting-state functional organization within the central executive network in obsessive-compulsive disorder.

AIM: Obsessive-compulsive disorder (OCD) is associated with deficits in response inhibition and planning, which are governed by the central executive network. The objective of this study was to investigate both intra- and inter-regional resting-state connectivity within the central executive network in OCD. METHODS: Thirty OCD patients and 30 matched healthy controls were scanned using resting-state functional magnetic resonance imaging. The independent component analysis was used on a separate sample of healthy controls to generate the central executive network mask for the subsequent OCD analyses. Regional homogeneity (ReHo) and seed-based functional connectivity analyses were used to explore the differences between intra- and inter-regional synchronized activity within the central executive network in OCD patients at rest. RESULTS: Increased ReHo and functional connectivity in the key regions of the central executive network, such as the orbitofrontal cortex, dorsolateral prefrontal cortex, and the angular gyrus, were found in OCD patients. Furthermore, changes in both the ReHo within the orbitofrontal cortex and the functional connectivity between the orbitofrontal cortex and angular gyrus were negatively correlated with OCD duration. CONCLUSION: The increased resting-state functional organization within the central executive network may be related to OCD patients' deficits in cognitive control and symptom progression.

[Genome-wide association studies on the developmental dyslexia children].

OBJECTIVE: To find out the potential polymorphisms of gene with developmental dyslexia children. METHODS: From January 2010 to December 2013, 121 cases children with developmental dyslexia and 117 cases health children as the control were enrolled into the study. The potential polymorphisms of gene were found by case-control study strategies based on the Affymetrix Genome-Wide SNP 6. 0 microarray and pathway analysis. RESULTS: Genotypes and allele frequencies of rs331142 and rs12495133 from DYX1C1 gene, rs11629841 and rs3743205 from ROBOl gene between cases and control groups were significantly different (P < 0. 05). CONCLUSION: Polymorphism of rs331142 and rs12495133 from DYX1C1 gene, rs11629841 and rs3743205 from ROB01 gene may associate with developmental dyslexia children.

Profile and mental health characterization of childhood overprotection/overcontrol experiences among Chinese university students: a nationwide survey.

Introduction: The childhood experiences of being overprotected and overcontrolled by family members have been suggested to be potentially traumatic. However, the possible associated factors of these experiences among young people are still not well studied. This study aimed to partly fill such gaps by a relatively large, nationwide survey of Chinese university students. Methods: A total of 5,823 university students across nine different provinces in China were included by the convenience sampling method in the data analyses. All participants completed the overprotection/overcontrol (OP/OC) subscale in a recently developed 33-item childhood trauma questionnaire (CTQ- 33). Data were also collected on all participants' socio-demographic profiles and characterization of mental health. Binary logistic regression was conducted to investigate the associated socio-demographic and psychological factors of OP/ OC. Results: The prevalence of childhood OP/OC was estimated as 15.63% (910/5,823) based on a cutoff OP/OC subscale score of ≥ 13. Binary logistic regression suggested that being male, being a single child, having depression, having psychotic-like experiences, lower family functioning, and lower psychological resilience were independently associated with childhood OP/OC experiences (all corrected-p < 0.05). The OP/OC was also positively associated with all the other trauma subtypes (abuses and neglects) in the CTQ-33, while there are both shared and unique associated factors between the OP/OC and other trauma subtypes. Post-hoc analyses suggested that OP/OC experiences were associated with depression in only females and associated with anxiety in only males. Discussion: Our results may provide initial evidence that childhood OP/OC experiences would have negative effects on young people's mental health which merits further investigations, especially in clinical populations.

Inhibition of MicroRNA-182/183 Cluster Ameliorates Schizophrenia by Activating the Axon Guidance Pathway and Upregulating DCC.

Schizophrenia (SZ) is a complex disorder caused by a variety of genetic and environmental factors. Mounting evidence suggests the involvement of microRNAs (miRNAs) in the pathology of SZ. Accordingly, the current study set out to investigate the possible implication of the miR-182/183 cluster, as well as its associated mechanism in the progression of SZ. Firstly, rat models of SZ were established by intraperitoneal injection of MK-801. Moreover, rat primary hippocampal neurons were exposed to MK-801 to simulate injury of hippocampal neurons. The expression of miR-182/183 or its putative target gene DCC was manipulated to examine their effects on SZ in vitro and in vivo. It was found that miR-182 and miR-183 were both highly expressed in peripheral blood of SZ patients and hippocampal tissues of SZ rats. In addition, the miR-182/183 cluster could target DDC and downregulate the expression of DDC. On the other hand, inhibition of the miR-182/183 cluster ameliorated SZ, as evidenced by elevated serum levels of NGF and BDNF, along with reductions in spontaneous activity, serum GFAP levels, and hippocampal neuronal apoptosis. Additionally, DCC was found to activate the axon guiding pathway and influence synaptic activity in hippocampal neurons. Collectively, our findings highlighted that inhibition of the miR-182/183 cluster could potentially attenuate SZ through DCC-dependent activation of the axon guidance pathway. Furthermore, inhibition of the miR-182/183 cluster may represent a potential target for the SZ treatment.

Sex difference in the prevalence of psychotic-like experiences in adolescents: results from a pooled study of 21,248 Chinese participants.

Psychotic-like experiences (PLEs) are subclinical psychotic symptoms in the general population which are linked to increased risks for later psychiatric disorders. Male and female adolescents were reported to experience PLEs differently, but the results were mixed in previous studies. This study aimed to investigate possible sex differences in the prevalence of adolescent PLEs using a large pooled sample. A total of 21,248 Chinese adolescents aged 11 to 19 years were included, which were drawn from five separate cross-sectional surveys undertaken between 2015 to 2021 in China. PLEs were measured by the 8-item Community Assessment of Psychic Experiences. Using binary logistic regression analyses, no significant sex differences were found in the overall prevalence of PLEs after controlling for age and dataset effects. As for specific PLE subtypes, however, being female was associated with a higher prevalence of delusion of reference and a lower prevalence of visual hallucinations. Furthermore, post-hoc subgroup analyses showed that the sex differences in visual hallucinations persist across both early (<= 14 years old) and late (> 14 years old) adolescence, while differences in the delusion of reference were significant in only early adolescence. These findings may help us to further understand the biological basis of PLEs.

The passive recipient: Neural correlates of negative self-view in depression.

INTRODCTION: Previous studies have argued that people tend to isolate themselves from negative information. This tendency is modulated by the individual's role in social interaction, that is, as an initiative actor (e.g., "I hit Tom") or a passive recipient (e.g., "Paul hits me"). Depressed patients tend to focus on negative aspects of themselves and cope with situations passively. It is still an open question how the actor/recipient role affects the behavioral and neural responses to self in depression. METHODS: The present study adopted functional magnetic resonance imaging (fMRI) technology to investigate behavioral and neural responses to self (as an actor/recipient) in depressed patients and the matched healthy controls when attributing negative events. RESULTS: Compared with healthy controls, depressed patients showed more self-attribution for negative events. Depressed patients showed increased brain activity in the dorsal medial prefrontal cortex (dmPFC) subsystem of the default mode network (DMN) when they played recipient role in self-related negative events. Activity of the dmPFC subsystem was negatively correlated with depressed patients' self-attribution for negative events in recipient condition. While decreased brain activity in the medial temporal lobe (MTL) subsystem was observed in depressed patients when they played the actor or recipient role in self-related negative events. Activity of the MTL subsystem was negatively correlated with depressed patients' reaction time when they played recipient role in selfrelated negative events. CONCLUSION: These results implicated that depressed patients manifested the negative self-view. Actor/recipient role affected their activation patterns in the DMN which were different from the healthy controls. The correlation between the abnormal brain activations of the DMN and the behavioral performances might manifest more easily when depressed patients played recipient role in negative events.

Altered Global Brain Functional Connectivity in Drug-Naive Patients With Obsessive-Compulsive Disorder.

Abnormal functional connectivity (FC) within discrete brain networks is involved in the pathophysiology of obsessive-compulsive disorder (OCD) with inconsistent results. In the present study, we investigated the FC patterns of 40 drug-naive patients with OCD and 38 healthy controls (HCs) through an unbiased voxel-wise global brain FC (GFC) analysis at rest. Compared with HCs, patients with OCD showed decreased GFC within the default mode network (DMN) (i.e., left posterior cingulate cortex/lingual gyrus) and sensorimotor network (i.e., left precentral gyrus/postcentral gyrus) and increased GFC within the executive control network (ECN) (i.e., left dorsal lateral prefrontal cortex and left inferior parietal lobule). Receiver operating characteristic curve analyses further indicated that the altered GFC values within the DMN, ECN, and sensorimotor network may be used as neuroimaging markers to differentiate patients with OCD from HCs. These findings indicated the aberrant FC patterns of the DMN, ECN, and sensorimotor network associated with the pathophysiology of OCD and provided new insights into the changes in brain organization function in OCD.

Static and dynamic functional connectivity of the prefrontal cortex during resting-state predicts self-serving bias in depression.

Major depression disorder (MDD) is characterized by the lack of self-serving bias, which may inherently underlie the onset and maintenance of depression. Emerging neuroimaging evidences have indicated that the altered self-processing in MDD may be germane to the dysfunctional static resting-state functional connectivity (RSFC) of the prefrontal cortex (PFC). Although static RSFC studies provide tremendous amounts of evidences on functional changes in depression, explorations of dynamic RSFC among the PFC and other brain regions may elucidate the temporal changes of neural activities associated with depression. To further explore the behavioral and neural correlates of self-serving bias, 21 depressed and 23 non-depressed individuals underwent resting-state functional magnetic resonance imaging (fMRI) scan and completed a self-serving bias task. Static and dynamic RSFC analyses were conducted for specific subregions of the PFC, including the dorsomedial prefrontal cortex (dmPFC), the orbitofrontal cortex (OFC), the ventral prefrontal cortex (vlPFC) and the anterior cingulate cortex. Depressed patients showed an attenuated self-serving bias as compared with controls, and aberrant static and dynamic RSFC among these subregions of the PFC. In particular, the self-serving bias was associated with static dmPFC-to-OFC RSFC and dynamic vlPFC-to-OFC RSFC for MDD group. The aberrant RSFC of the PFC may serve as a predictor for self-serving bias in depression.

Axon guidance pathway genes are associated with schizophrenia risk.

In the present study, we analyzed schizophrenia (SCZ)-related genome-wide association studies (GWAS) to identify genes and pathways associated with SCZ. We identified 1,098 common genes (1,098/9,468) and 20 shared KEGG pathways (both P<0.01) by integrating candidate genes from the European and American SCZ-related GWAS. The pathways related to axon guidance, long term potentiation and arrhythmogenic right ventricular cardiomyopathy (ARVC) were highly significant (P<10-3). Moreover, 15 axon guidance pathway-related genes were associated with SCZ. The association between axon guidance pathway genes and SCZ was validated by a two-stage case-control study on Shandong migrants in northeastern China. Moreover, individuals with the rs9944880 TT polymorphism in the deleted in colorectal cancer (DCC) gene were associated with SCZ. These findings indicate that the axon guidance pathway genes and the rs9944880 SNP in DCC gene are associated with SCZ pathogenesis.

Association between C-reactive protein and risk of schizophrenia: An updated meta-analysis.

C-reactive protein (CRP) has been indicated to be associated with the pathogenesis of schizophrenia (SZ) and other psychiatric disorders. The aim of this study is to investigate whether peripheral blood CRP levels are associated with the risk of SZ. We searched literature from databases of Pubmed, Embase and the Cochrane Library from inception to November 1, 2016 for studies that reported serum or plasma CRP levels in patients with SZ and non-SZ controls. At least two reviewers decided on eligibility and extracted data from included studies. Random effects meta-analyses were performed using standardized mean difference (SMD) as the effect estimate of the differences in CRP levels between subjects with SZ and healthy controls. We identified 18 studies representing 1963 patients with SZ and 3683 non-SZ controls. Compared with non-schizophrenics, blood CRP levels were moderately increased in people with SZ (SMD 0.53, 95% CI 0.30 to 0.76) irrespective of study region, sample size of included studies, patient mean age, age of SZ onset and patient body mass index. Publication bias was not detected through Egger's linear regression test (P = 0.292). We noticed that patients in Asia or Africa (n = 6, SMD 0.73, 95% CI 0.26 to 1.21) and whose age less than 30 years (n = 5, SMD 0.76, 95% CI 0.07 to 1.58) had substantially higher CRP levels. Our study provides evidence that higher CRP levels are associated with increased risk of SZ, especially for young adult patients less than 30 years. Further large-scale studies are strongly warranted to further confirm this association.

Effects of Common Polymorphisms in the MTHFR and ACE Genes on Diabetic Peripheral Neuropathy Progression: a Meta-Analysis.

Diabetic peripheral neuropathy (DPN) is a microvascular complication of diabetes mellitus. The aim of this meta-analysis was to evaluate the effects of methylenetetrahydrofolate reductase (MTHFR) 677 C>T and ACE I/D polymorphisms in the development of DPN. We systematically reviewed published studies on MTHFR 677 C>T and ACE I/D polymorphisms and DPN found in various types of electronic databases. Strengthening the Reporting of Observational studies in Epidemiology (STROBE) quality score systems were used to determine the quality of the articles selected for inclusion. Odds ratios (ORs) and its corresponding 95 % confidence interval (95 % CI) were calculated. We used STATA statistical software (version 12.0, Stata Corporation, College Station, TX, USA) to deal with statistical data. Our results indicated an association of ACE D>I mutation (OR = 1.43, 95 % CI 1.12-1.83, P = 0.004) and MTHFR 677 C>T mutation (OR = 1.43, 95 % CI 1.08-1.90, P = 0.014) with DPN under the allele model, and similar results were also found under the dominant model (all P < 0.05). Subgroup analysis by country indicated that the MTHFR 677 C>T polymorphism may be the main risk factor for DPN in Turkey under four genetic models. ACE D>I mutation was correlated with DPN in Japanese and Pakistani populations in the majority of groups. The relationships of MTHFR 677 C>T and ACE I/D polymorphisms with DPN patients presented in this meta-analyses support the view that the MTHFR and ACE genes might play an important role in the development of DPN.

Abnormal resting-state functional connectivity of the left caudate nucleus in obsessive-compulsive disorder.

Altered brain activities in the cortico-striato-thalamocortical (CSTC) circuitry are implicated in the pathophysiology of obsessive-compulsive disorder (OCD). However, whether the underlying changes occur only within this circuitry or in large-scale networks is still not thoroughly understood. This study performed voxel-based functional connectivity analysis on resting-state functional magnetic resonance imaging (fMRI) data from thirty OCD patients and thirty healthy controls to investigate whole-brain intrinsic functional connectivity patterns in OCD. Relative to the healthy controls, OCD patients showed decreased functional connectivity within the CSTC circuitry but increased functional connectivity in other brain regions. Furthermore, decreased left caudate nucleus-thalamus connectivity within the CSTC circuitry was positively correlated with the illness duration of OCD. This study provides additional evidence that CSTC circuitry may play an essential role and alteration of large-scale brain networks may be involved in the pathophysiology of OCD.

Data on the impact of SSRIs and depression symptoms on the neural activities in obsessive-compulsive disorder at rest.

The data provided here related to our research article (Chen et al., 2016) [1]. We provide whole-brain intrinsic functional connectivity patterns in obsessive-compulsive disorder at resting-state [1]. This article also provides supplementary information to our research article, i.e., between - group comparisons of the effect of selective serotonin reuptake inhibitors (SSRIs) and combined depression symptoms on resting-state neural activities in obsessive-compulsive disorder. The data presented here provide novel insights into the effect of SSRIs and combined depression symptoms on the neural activities at rest.

Anxiolytic Effects of Royal Sun Medicinal Mushroom, Agaricus brasiliensis (Higher Basidiomycetes) on Ischemia-Induced Anxiety in Rats.

We investigated the anxiolytic effects Agaricus brasiliensis extract (AbSE) on ischemia-induced anxiety using the plus-maze test and the social interaction test. The animals were treated orally with AbSE (4, 8, and 10 mg/kg/d, respectively) for 30 d, followed by middle cerebral artery occlusion-induced cerebral ischemia. Levels of noradrenaline, dopamine, and serotonin in the cerebral cortex of rats, as well as oxidative stress and plasma corticosterone levels were analyzed, respectively. The rota-rod test was carried out to exclude any false positive results in experimental procedures related to anxiety disorders, and the catalepsy test was carried out to investigate whether AbSE induces catalepsy. Our results demonstrate that oral administration of AbSE presented anxiolytic-like effects in the elevated plus-maze test and the social interaction test. Furthermore, AbSE did not induce extrapyramidal symptoms in the catalepsy test. The mechanism underlying the anxiolytic effect of AbSE might be increased brain monoamine levels and plasma corticosterone levels and decreased oxidative stress in cerebral ischemia/reperfusion rats.

Influence of GNB3 C825T polymorphism on the efficacy of antidepressants in the treatment of major depressive disorder: A meta-analysis.

OBJECTIVE: We performed the present meta-analysis in order to evaluate the influence of a common polymorphism (C825T, rs5443 C>T) in the GNB3 gene on the efficacy of antidepressants in the treatment of major depressive disorder (MDD). METHOD: A relevant literature was searched using the PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, CBM and CNKI databases without any language restrictions. STATA Version 12.0 software (Stata Corporation, College Station, Texas USA) was used for this meta-analysis. Odds ratio (OR) and its corresponding 95% confidence interval (95% CI) were calculated. RESULTS: Our findings suggested that the GNB3 C825T polymorphism was significantly correlated with a higher response rate to antidepressants in MDD patients under the allele and dominant models. Furthermore, we found significant associations between GNB3 C825T polymorphisms and antidepressant-induced remission in MDD patients. Ethnicity-stratified analysis indicated that GNB3 C825T polymorphisms may be strongly related to the efficacy of antidepressants in the treatment of MDD among Asians, but not in Caucasians (all P>0.05). CONCLUSION: Our findings provide empirical evidence that GNB3 C825T polymorphisms may be correlated with the efficacy of antidepressants in the treatment of MDD, especially among Asians patients.