Rational use of mesenchymal stem cells in the treatment of autism spectrum disorders

Autism and autism spectrum disorders(ASD) refer to a range of conditions characterized by impaired social and communication skills and repetitive behaviors caused by different combinations of genetic and environmental influences. Although the pathophysiology underlying ASD is still unclear, recent evidence suggests that immune dysregulation and neuroinflammation play a role in the etiology of ASD. In particular, there is direct evidence supporting a role for maternal immune activation during prenatal life in neurodevelopmental conditions. Currently, the available options of behavioral therapies and pharmacological and supportive nutritional treatments in ASD are only symptomatic. Given the disturbing rise in the incidence of ASD, and the fact that there is no effective pharmacological therapy for ASD, there is an urgent need for new therapeutic options. Mesenchymal stem cells(MSCs) possess immunomodulatory properties that make them relevant to several diseases associated with inflammation and tissue damage. The paracrine regenerative mechanisms of MSCs are also suggested to be therapeutically beneficial for ASD.Thus the underlying pathology in ASD, including immune system dysregulation and inflammation, represent potential targets for MSC therapy. This review willfocus on immune dysfunction in the pathogenesis of ASD and will further discuss the therapeutic potential for MSCs in mediating ASD-related immunological disorders.

Shuganjieyu capsule increases neurotrophic factor expression in a rat model of depression

Shuganjieyu capsule has been approved for clinical treatment by the State Food and Drug Administration of China since 2008. In the clinic, Shuganjieyu capsule is often used to treat mild to moderate depression. In the rat model of depression established in this study, Shuganjieyu capsule was administered intragastrically daily before stress. Behavioral results confirmed that depressive symptoms lessened after treatment with high-dose(150 mg/kg) Shuganjieyu capsule. Immunohistochemistry results showed that high-dose Shuganjieyu capsule significantly increased phosphorylation levels of phosphorylation cyclic adenosine monophosphate response element binding protein and brain-derived neurotrophic factor expression in the medial prefrontal cortex and hippocampal CA3 area. Overall, our results suggest that in rats, Shuganjieyu capsule effectively reverses depressive-like behaviors by increasing expression levels of neurotrophic factors in the brain.

Prevalence of depressive and anxiety disorders in Chinese gastroenterological outpatients

AIM:To investigate the prevalence and physicians' detection rate of depressive and anxiety disorders in gastrointestinal(GI)outpatients across China. METHODS:A hospital-based cross-sectional survey was conducted in the GI outpatient departments of 13 general hospitals.A total of 1995 GI outpatients were recruited and screened with the Hospital Anxiety and Depression Scale(HADS).The physicians of the GI departments performed routine clinical diagnosis and management without knowing the HADS score results.Subjects with HADS scores≥8 were subsequently interviewed by psychiatrists using the Mini International Neuropsy-chiatric Interview(MINI)to make further diagnoses. RESULTS:There were 1059 patients with HADS score ≥8 and 674(63.64%)of them undertook the MINI interview by psychiatrists.Based on the criteria of Diagnostic and Statistical Manual of Mental Disorders (4th edition),the adjusted current prevalence for depressive disorders,anxiety disorders,and comorbidity of both disorders in the GI outpatients was 14.39%, 9.42%and 4.66%,respectively.Prevalence of depressive disorders with suicidal problems[suicide attempt or suicide-related ideation prior or current;module C (suicide)of MINI score≥1]was 5.84%in women and 1.64%in men.The GI physicians'detection rate of depressive and anxiety disorders accounted for 4.14%. CONCLUSION:While the prevalence of depressive and anxiety disorders is high in Chinese GI outpatients, the detection rate of depressive and anxiety disorders by physicians is low.

男性住院精神分裂症患者的攻击行为特征研究（英文）

背景:精神分裂症等重性精神障碍患者攻击行为发生率高于普通人群,相关因素的探讨对于该人群攻击行为的预防和干预有重要意义。目的:了解某综合医院精神科男性住院精神分裂症患者的攻击行为特征。方法:采用连续取样法,收集了75例自2015年8月至2016年2月在中南大学湘雅二医院精神科男病房住院的精神分裂症患者。使用自编的一般情况调查问卷、修订版外显攻击行为量表(MOAS)、暴力历史、临床、风险评估量表(HCR-20)、精神病态清单(PCL-R)、阳性与阴性症状量表(PANSS)在入院后3天内对患者进行评估。根据MOAS各项的得分,将研究对象分为攻击组(39例)和非攻击组(36例),比较两组间在社会人口学特征以及各个评估工具上得分的差异。结果:HCR-20中的H1(既往暴力事件)、H2(年轻时的暴力事件)、H10(既往不服从管教)、C4(冲动性),PCL-R的反社会因子,PANSS的激活性症状群、偏执症状群、抑郁症状群在攻击组得分高于非攻击组,且差异有统计学显著性。结论:有暴力行为史,既往不服管教,具有反社会人格特征,表现冲动,伴有焦虑抑郁情绪可能是男性住院精神分裂症患者发生攻击行为的相关因素。

Efficacy of Williams LifeSkills Training in improving psychological health of Chinese male juvenile violent offenders:a randomized controlled study

This randomized controlled study was conducted to evaluate the efficacy of Williams Life Skills Training(WLST) as a means ofimproving the psychological health of Chinese male juvenile violent offenders.Sixty-six participants were assigned randomly to receive the usual intervention plus 8 weeks of WLST(study group,n = 33) or only the usual intervention(control group,n = 33). We found that the study group exhibited significantly decreased State-Trait Anxiety Inventory(STAI X-1,X-2) STAX2 scores and Trait Coping Style Questionnaire(TCSQ) negative scores,and increased Interpersonal Support Evaluation List(ISEL) tangible scores from baseline to 9 weeks later(P <0.01). In addition,a between-group difference in changes of TCSQ negative score was observed at the end of week 9(P <0.05). These fi ndings suggest that WLST can improve trait anxiety,coping style,and interpersonal support in male Chinese juvenile violent offenders.

Involuntary admission and treatment of patients with mental disorder

Despite the efforts of the World Health Organization to internationally standardize strategies for mental-health care delivery,the rules and regulations for involuntary admission and treatment of patients with mental disorder still differ markedly across countries. This review was undertaken to describe the regulations and mental-health laws from diverse countries and districts of Europe(UK,Austria,Denmark,France,Germany,Italy,Ireland,and Norway),the Americas(Canada,USA,and Brazil),Australasia(Australia and New Zealand),and Asia(Japan and China). We outline the criteria and procedures for involuntary admission to psychiatric hospitals and to community services,illustrate the key features oflaws related to these issues,and discuss their implications for contemporary psychiatric practice. This review may help to standardize the introduction oflegislation that allows involuntary admission and treatment of patients with mental disorders in the mainland of China,and contribute to improved mental-health care. In this review,involuntary admission or treatment does not include the placement of mentally-ill offenders,or any other aspect of forensic psychiatry.

嵌合蛋白-2基因启动子区甲基化改变可能与甲基苯丙胺成瘾有关（英文）

背景:甲基苯丙胺(Methamphetamine,MA)滥用情况在我国十分严峻,已成为我国第一大毒品。甲基苯丙胺依赖的机制尚不完全清楚。CHN2基因编码嵌合蛋白-2,该蛋白可通过Rac GTP酶系统调控轴突修剪,在神经系统功能环路的形成中起关键作用。遗传学研究显示该基因的多态性与物质依赖形成相关。目的 :本研究旨在研究CHN2基因启动子区甲基化改变与甲基苯丙胺依赖的关系,以探索甲基苯丙胺依赖的新机制。方法 :采用美国精神障碍诊断与统计手册第四版(DSM-IV)轴I障碍定式检查工具中文版对强制戒毒所的甲基苯丙胺依赖者进行调查,筛选出224名男性依赖者纳入病例组。另外选择年龄匹配的109名身体健康的男性作为对照组。采取受检者静脉血液,采用Methylight qPCR技术测定CHN2基因启动子区甲基化状态,统计分析比较两组的检测结果。结果 :甲基苯丙胺依赖组CHN2基因启动子区甲基化程度为2795.55(733.19),显著高于正常对照组的1026.73(698.73),(t=21.25,p<0.001)。相关分析显示CHN2基因启动子区甲基化程度与开始使用甲基苯丙胺的年龄、使用甲基苯丙胺的总时间、合并使用其它精神活性物质(K粉、烟草、和酒精)无明显关联。结论 :CHN2基因启动子区甲基化改变与甲基苯丙胺依赖显著相关。

Face and object visual working memory deficits in first-episode schizophrenia correlate with multiple neurocognitive performances

Background Working memory(WM)deficit is considered a core feature and cognitive biomarker in patients with schizophrenia.Several studies have reported prominent object WM deficits in patients with schizophrenia,suggesting that visual WM in these patients extends to non-spatial domains.However,whether non-spatial WM is similarly affected remains unclear.Aim This study primarily aimed to identify the processing of visual object WM in patients with first-episode schizophrenia.Methods The study included 36 patients with first-episode schizophrenia and 35 healthy controls.Visual object WM capacity,including face and house WM capacity,was assessed by means of delayed matching-to sample visual WM tasks,in which participants must distribute memory so that they can discriminate a target sample.We specifically examined their anhedonia experience by the Temporal Experience of Pleasure Scale and the Snaith-Hamilton Pleasure Scale.Cognitive performance was measured by the Repeatable Battery for the Assessment of Neuropsychological Status(RBANS).Results Both face and house WM capacity was significantly impaired in patients with schizophrenia.For both tasks,the performance of all the subjects was worse under the high-load condition than under the low-load condition.We found that WM capacity was highly positively correlated with the performance on RBANS total scores(r=−0.528,p=0.005),RBANS delayed memory scores(r=−0.470,p=0.013),RBANS attention scores(r=−0.584,p=0.001),RBANS language scores(r=−0.448,p=0.019),Trail-Making Test:Part A raw scores(r=0.465,p=0.015)and simple IQ total scores(r=−0.538,p=0.005),and correlated with scores of the vocabulary test(r=−0.490,p=0.011)and scores of the Block Diagram Test(r=−0.426,p=0.027)in schizophrenia.No significant correlations were observed between WM capacity and Positive and Negative Syndrome Scale symptoms.Conclusions Our research found that visual object WM capacity is dramatically impaired in patients with schizophrenia and is strongly correlated with other measures of cognition,suggesting a mechanism that is critical in explaining a portion of the broad cognitive deficits observed in schizophrenia.

Brain structure in post-traumatic stress disorder A voxel-based morphometry analysis

This study compared the difference in brain structure in 12 mine disaster survivors with chronic post-traumatic stress disorder,7 cases of improved post-traumatic stress disorder symptoms,and 14 controls who experienced the same mine disaster but did not suffer post-traumatic stress disorder,using the voxel-based morphometry method.The correlation between differences in brain structure and post-traumatic stress disorder symptoms was also investigated.Results showed that the gray matter volume was the highest in the trauma control group,followed by the symptoms-improved group,and the lowest in the chronic post-traumatic stress disorder group.Compared with the symptoms-improved group,the gray matter volume in the lingual gyrus of the right occipital lobe was reduced in the chronic post-traumatic stress disorder group.Compared with the trauma control group,the gray matter volume in the right middle occipital gyrus and left middle frontal gyrus was reduced in the symptoms-improved group.Compared with the trauma control group,the gray matter volume in the left superior parietal lobule and right superior frontal gyrus was reduced in the chronic post-traumatic stress disorder group.The gray matter volume in the left superior parietal lobule was significantly positively correlated with the State-Trait Anxiety Inventory subscale score in the symptoms-improved group and chronic post-traumatic stress disorder group(r=0.477,P=0.039).Our findings indicate that(1) chronic post-traumatic stress disorder patients have gray matter structural damage in the prefrontal lobe,occipital lobe,and parietal lobe,(2) after post-traumatic stress,the disorder symptoms are improved and gray matter structural damage is reduced,but cannot recover to the trauma-control level,and(3) the superior parietal lobule is possibly associated with chronic post-traumatic stress disorder.Post-traumatic stress disorder patients exhibit gray matter abnormalities.

Rare inherited missense variants of POGZ associate with autism risk and disrupt neuronal development

Excess de novo likely gene-disruptive and missense variants within dozens of genes have been identified in autism spectrum disorder(ASD)and other neurodevelopmental disorders.However,many rare inherited missense variants of these high-risk genes have not been thoroughly evaluated.In this study,we analyzed the rare missense variant burden of POGZ in a large cohort of ASD patients from the Autism Clinical and Genetic Resources in China(ACGC)and further dissected the functional effect of diseaseassociated missense variants on neuronal development.Our results showed a significant burden of rare missense variants in ASD patients compared to the control population(P=4.6×10-5,OR=3.96),and missense variants in ASD patients showed more severe predicted functional outcomes than those in controls.Furthermore,by leveraging published large-scale sequencing data of neurodevelopmental disorders(NDDs)and sporadic case reports,we identified 8 de novo missense variants of POGZ in NDD patients.Functional analysis revealed that two inherited,but not de novo,missense variants influenced the cellular localization of POGZ and failed to rescue the defects in neurite and dendritic spine development caused by Pogz knockdown in cultured mouse primary cortical neurons.Significantly,L1CAM,an autism candidate risk gene,is differentially expressed in POGZ deficient cell lines.Reduced expression of L1cam was able to partially rescue the neurite length defects caused by Pogz knockdown.Our study showed the important roles of rare inherited missense variants of POGZ in ASD risk and neuronal development and identified the potential downstream targets of POGZ,which are important for further molecular mechanism studies.

Grey matter volume abnormalities in patients with bipolar I depressive disorder and unipolar depressive disorder:a voxelbased morphometry study

Bipolar disorder and unipolar depressive disorder(UD) may be different in brain structure. In the present study,we performed voxel-based morphometry(VBM) to quantify the grey matter volumes in 23 patients with bipolar I depressive disorder(BP1) and 23 patients with UD,and 23 age-,gender-,and educationmatched healthy controls(HCs) using magnetic resonance imaging. We found that compared with the HC and UD groups,the BP1 group showed reduced grey matter volumes in the right inferior frontal gyrus and middle cingulate gyrus,while the UD group showed reduced volume in the right inferior frontal gyrus compared to HCs. In addition,correlation analyses revealed that the grey matter volumes of these regions were negatively correlated with the Hamilton depression rating scores. Taken together,the results of our study suggest that decreased grey matter volume of the right inferior frontal gyrus is a common abnormality in BP1 and UD,and decreasedgrey matter volume in the right middle cingulate gyrus may be specifi c to BP1.

A novel missense variant in ACAA1 contributes to early-onset Alzheimer’s disease,impairs lysosomal function,and facilitates amyloid-p pathology and cognitive decline

Alzheimer’s disease(AD)is characterized by progressive synaptic dysfunction,neuronal death,and brain atrophy,with amyloid-p(Ap)plaque deposits and hyperphosphorylated tau neurofibrillary tangle accumulation in the brain tissue,which all lead to loss of cognitive function.Pathogenic mutations in the well-known AD causal genes including APP,PSEN1,and PSEN2 impair a variety of pathways,including protein processing,axonal transport,and metabolic homeostasis.Here we identified a missense variant rs117916664(c.896T>C,p.Asn299Ser[p.N299S])of the acetyl-CoA acyltransferase 1(ACM1)gene in a Han Chinese AD family by whole-genome sequencing and validated its association with early-onset familial AD in an independent cohort.Further in vitro and in vivo evidence showed that ACAA1 p.N299S contributes to AD by disturbing its enzymatic activity,impairing lysosomal function,and aggravating the Ap pathology and neuronal loss,which finally caused cognitive impairment in a murine model.Our findings reveal a fundamental role of peroxisome-mediated lysosomal dysfunction in AD pathogenesis.

An update on research and approaches in biological psychiatry

Many studies have shown that,in terms of global burden,mental disorders have exceeded diseases of the cardiovascular and respiratory systems as well as malignant tumors.Nevertheless,the pathological mental activities caused by the millions of neurons in the human brain are far less clear than diseases of other organs and systems.This is not only due to the limited approaches to exploring the human brain,but also the multiple mechanisms