Why sex differences in schizophrenia？

Clinical observation shows that men and women are different in prevalence, symptoms, and responses to treatment of several psychiatric disorders, including schizophrenia. While the etiology of gender differences in schizophrenia is only partially understood, recent genetic studies suggest significant sex-specific pathways in the schizophrenia between men and women. More research is needed to understand the causal roles of sex differences in schizophrenia in order to ultimately develop sex-specific treatment of this serious mental illness. In the present review, we will out-line the current evidence on the sex-related factors interaction with disease onset, symptoms and treatment of schizophrenia, and discuss the potential molecular mechanisms that may mediate their cooperative actions in schizophrenia pathogenesis.

Prepulse inhibition deficits in antipsychotic-na-ve first-episode schizophrenia:a meta-analysis

Objective:Published studies have found prepulse inhibition(PPI)in schizophrenia is impaired,suggesting PPI may be a biomarker of schizophrenia.We aim to examine whether PPI deficits exist in antipsychotic-na-ve,first-episode schizophrenia,and evaluate the effect size of PPI deficits between patients and healthy controls.Methods:The effect size of PPI deficits was evaluated for PPI%by calculating standard mean differences(SMDs)between patients with antipsychotic-na-ve,first-episode schizophrenia and healthy controls.Results:Twelve studies met the inclusion criteria,consisting390antipsychotic-na-ve,first-episode schizophrenia and406healthy controls.The effect sizes of76dB PPI in60ms and120ms interstimulus interval(ISI)were-0.19and-0.41respectively,and the76dB PPI overall effect size was-0.30.The effect sizes of85/86dB PPI in30ms,60ms and120ms ISI were-0.25,-0.42and-0.59respectively,and the85/86dB PPI overall effect size was-0.46.One study were excluded due to heterogeneity in the85/86dB,120ms ISI group,the pooled effect size of the PPI differences between patient group and health control dropped to-0.42,and the overall effect size changed to-0.39.There were no statistical differences in startle magnitude(overall effect size=-0.18)and habituation%(overall effect size=-0.17)between patients and healthy controls.Conclusions:Antipsychotic-na-ve,first-episode schizophrenia patients exhibit robust and reliable deficits in PPI,85/86dB PPI deficit was more severe than76dB PPI,and85/86dB,60-ms ISI PPI was more likely to be a biomarker for schizophrenia,it suggested that the parameters of PPI are particularly significant to affect the effect size so that should be interpreted with cautions in the future studies.

Whole-genome sequencing of monozygotic twins discordant for schizophrenia indicates multiple genetic risk factors for schizophrenia

Schizophrenia is a common disorder with a high heritability, but its genetic architecture is still elusive.We implemented whole-genome sequencing(WGS) analysis of 8 families with monozygotic(MZ) twin pairs discordant for schizophrenia to assess potential association of de novo mutations(DNMs) or inherited variants with susceptibility to schizophrenia. Eight non-synonymous DNMs(including one splicing site) were identified and shared by twins, which were either located in previously reported schizophrenia risk genes(p.V24689 I mutation in TTN, p.S2506 T mutation in GCN1L1, IVS3+1G > T in DOCK1) or had a benign to damaging effect according to in silico prediction analysis. By searching the inherited rare damaging or loss-of-function(LOF) variants and common susceptible alleles from three classes of schizophrenia candidate genes, we were able to distill genetic alterations in several schizophrenia risk genes, including GAD1, PLXNA2, RELN and FEZ1. Four inherited copy number variations(CNVs; including a large deletion at 16p13.11) implicated for schizophrenia were identified in four families, respectively. Most of families carried both missense DNMs and inherited risk variants, which might suggest that DNMs, inherited rare damaging variants and common risk alleles together conferred to schizophrenia susceptibility. Our results support that schizophrenia is caused by a combination of multiple genetic factors, with each DNM/variant showing a relatively small effect size.

中国精神分裂症患者失匹配负波特征的Meta分析（英文）

背景:国外对精神分裂症患者失匹配负波(mismatch negativity,MMN)波幅进行Meta分析发现其明显低于健康对照组,区分效应值(Cohen’s d,)d在1.00左右,使之可能成为精神分裂症早期诊断的生物标志物。但检索文献未发现纳入中国精神分裂症人群MMN研究的Meta分析报道,因此有必要对中国精神分裂症患者的MMN进行Meta分析。目的:通过Meta分析计算中国精神分裂症患者MMN的平均效应值,探讨其是否可作为中国精神分裂症患者的生物标志物。方法:计算机检索中国知网(China National Knowledge Infrastructure,CKNI)、万方数据库(WanF ang Data)、维普数据库(Vip Citation Databases,VIP)、PubM ed数据库,收集2017年5月8日前公开发表的关于中国汉族精神分裂症患者MMN研究的相关文献。MMN受损的影响通过计算精神分裂症患者组和健康对照组之间的标准平均差(SMDs)来评估MMN波幅。结果:共有11篇文献纳入分析。Newcastle-Ottawa Scale(NOS)评估所有研究的总体质量超过6。这些研究的meta分析数据包括精神分裂症患者432例,健康对照人群392例。Meta分析结果显示,精神分裂症组与健康对照组相比MMN受损显著(Cohen’s d=1.004)。剔除异质性大的文献2个,患者组和健康对照组之间MMN差异的效应值降为0.79(Cohen’s d=0.79)。亚组分析显示精神分裂症病程大于3年的患者MMN波幅缺失的效应值为0.95,而病程小于3年的效应值为0.77。通过Egger回归分析得出的发表偏移(t=1.83;p=0.101)提示没有发表偏移。结论:中国精神分裂症患者和健康对照者之间的MMN波幅效应值与其他关于该研究的meta分析结果是一致的,提示中国汉族精神分裂症患者也表现有MMN受损。

Using eye movements in the dot-probe paradigm to investigate attention bias in illness anxiety disorder

BACKGROUND Illness anxiety disorder(IAD)is a common,distressing,and debilitating condition with the key feature being a persistent conviction of the possibility of having one or more serious or progressive physical disorders.Because eye movements are guided by visual-spatial attention,eye-tracking technology is a comparatively direct,continuous measure of attention direction and speed when stimuli are oriented.Researchers have tried to identify selective visual attention biases by tracking eye movements within dot-probe paradigms because dot-probe paradigm can distinguish these attentional biases more clearly.AIM To examine the association between IAD and biased processing of illness-related information.METHODS A case-control study design was used to record eye movements of individuals with IAD and healthy controls while participants viewed a set of pictures from four categories(illness-related,socially threatening,positive,and neutral images).Biases in initial orienting were assessed from the location of the initial shift in gaze,and biases in the maintenance of attention were assessed from the duration of gaze that was initially fixated on the picture per image category.RESULTS The eye movement of the participants in the IAD group was characterized by an avoidance bias in initial orienting to illness-related pictures.There was no evidence of individuals with IAD spending significantly more time viewing illness-related images compared with other images.Patients with IAD had an attention bias at the early stage and overall attentional avoidance.In addition,this study found that patients with significant anxiety symptoms showed attention bias in the late stages of attention processing.CONCLUSION Illness-related information processing biases appear to be a robust feature of IAD and may have an important role in explaining the etiology and maintenance of the disorder.

Different aspects of cognitive function in adult patients with moyamoya disease and its clinical subtypes

Objective Although a few reports suggested that cognitive function impairment could be found in adult patients with moyamoya disease(MMD),there were still many aspects that are unclear.The aim of our study was to assess the cognitive function of adult patients with MMD and its clinical subtypes.Methods 49 patients with MMD and 23 healthy controls were asked to take cognitive function tests.Cognitive function tests included IQ,prospective memory(PM),immediate memory(IM),verbal fluency(VF),visual breadth,attention,retrospective memory(RM),Stroop test,Wisconsin Card Sorting Test,Trail-Making Test Part A(TMT-A)and Continuous Performance Test(CPT).Independent t-analysis,one-way analysis of variance and Pearson correlation were used to seek for differences between subgroups and the correlation between cognitive variables.results Compared with healthy controls,adult patients with MMD had a comprehensive cognitive impairment,including IQ,PM,VF,attention,RM,Stroop,CPT and TMT-A,with more serious impairment in PM and attention.PM and RM were separated,indicating that they were independent of each other.Pattern of attention was significantly different from healthy controls.Female patients were better than male patients,where significant differences in PM,IM,Stroop and WCST could be found.The haemorrhagic patients exhibited poorer in the dimension of PM and RM than the ischaemic.The headache subtype exhibited poorer than healthy controls.PM,RM,attention and executive function were moderately correlated with each other.Conclusions Adult patients with MMD had a wide range of cognitive impairment with more serious impairment in memory and attention.Differences in cognitive function existed between the different subtypes of adult MMD.

Neuropsychological impairment: the disturbed effect of self-processing in patients with major depressive disorder

Neuropsychological impairment has long been established as a fundamental characteristic of depression,but a generally accepted, specific pattern of neuropsychological impairment has not been summarized. In this study,we examined the classic neuropsychological paradigm of self-face recognition, to explore whether the self was impaired in major depressive disorder(MDD). Eighteen MDD patients and 20 healthy subjects were recruited to participate in this study. By using a face morphing technique, we measured the size of processing bias in MDD patients during different face discrimination tasks relative to controls. Results of analysis of variance(ANOVA) showed a significant main effect of Group(F(1, 36)= 7.388, P =0.01). Subsequent independent t-tests further revealed that self bias(t = 2.636, P = 0.012) and self-recognition bias(t = 2.190, P = 0.035) observed in self-famous task and self-stranger task respectively for patients were significantly greater than that for controls. Both self-processing and selfrecognition were impaired in patients with MDD, indicating that MDD individuals might exist level of self-abnormalities. These findings provide a new perspective for further study on the etiological and pathological mechanisms of MDD.

Role of FK506-binding protein in Ca^(2+) spark regulation

The elementary Ca^2＋ release events, Ca2＋ sparks, has been found for a quarter of century. However, the molecular regulation of the spark generator, the ryanodine receptor （RyR） on the sarcoplasmic reticulum, remains obscure. Although each subunit of the RyR homotetramer has a site for FKS06-binding protein （FKBP）, the role of FKBPs in modifying RyR Ca^2＋ sparks has been debated for long. One of the reasons behind the controversy is that most previous studies detect spontaneous sparks, where the mixture with out-of-focus events and local wavelets prevents an accurate characterization of Ca^2＋ sparks. In the pre- sent study, we detected Ca^2＋ sparks triggered by single L-type Ca^2＋ channels （LCCs） under loose-seal patch clamp conditions in FKS06-treated or FKBPI2.6 knockout cardiomyocytes. We found that FKBP dissociation both by FKS06 and by rapamycin decreased the Ca^2＋ spark amplitude in ventricular cardiomyocytes. This change was neither due to decreased releasable Ca^2＋ in the sarcoplasmic reticulum, nor explained by changed RyR sensitivity. Actually FKS06 increased the LCC-RyR coupling probability and curtailed the latency for an LCC to trigger a RyR Ca^2＋ spark. FKBP12.6 knockout had similar effects as FKS06/rapamycin treatment, indicating that the decreased spark amplitude was attributable to the dissociation of FKBP12.6 rather than FKBP12. We also explained how decreased amplitude of spontaneous sparks after FKBP dissociation sometimes appears to be increased or unchanged due to inappropriate data processing. Our results provided firm evidence that without the inter-RyR coordination by functional FKBP12.6, the RyR recruitment during a Ca^2＋ spark would be compromised despite the sensitization of individual RyRs.

Association between Tourette Syndrome and the Dopamine D3 Receptor Gene Rs6280

Background：Tourette syndrome （TS） is a complex,heterozygous genetic disorder.The number of molecular genetic studies have investigated several candidate genes,particularly those implicated in the dopamine system.The dopamine D3 receptor （DRD3） gene has been considered as a candidate gene in TS.There was not any report about the association study of TS and DRD3 gene in Han Chinese population.We combined a case-control genetic association analysis and nuclear pedigrees transmission disequilibrium test （TDT） analysis to investigate the association between DRD3 gene rs6280 single nucleotide polymorphisms （SNPs） and TS in a Han Chinese population.Methods：A total of 160 TS patients was diagnosed by the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition.The DRD3 gene rs6280 SNPs were genotyped by TaqMan SNP genotyping assay technique in all subjects.We used a case-control genetic association analysis to compare the difference in genotype and allele frequencies between 160 TS patients and 90 healthy controls.At the same time,we used TDT analysis to identify the DRD3 gene rs6280 transmission disequilibrium among 10l nuclear pedigrees.Results：The genotype and allele frequency of DRD3 gene rs6280 SNPs had no statistical difference between control group （90） and TS group （160） （χ^2 =3.647,P =0.161; χ^2 =0.643,P =0.423） using Chi-squared test.At the basis of the 101 nuclear pedigrees,TDT analysis showed no transmission disequilibrium ofDRD3 gene rs6280 SNPs （χ^2 =0; P =1）.Conclusions：Our findings provide no evidence for an association between DRD3 gene rs6280 and TS in the Han Chinese population.