A De Novo Variant Identified in the PPP2R1A Gene in an Infant Induces Neurodevelopmental Abnormalities

Dear Editor,Neurodevelopmental disorders include a wide range of conditions such as epilepsy,intellectual disability,and autism spectrum disorder.These disorders commonly cooccur in patients,which suggests that they share a common etiology[1,2].Genetic advances resulting from sequencing techniques over the past few years have greatly expanded our understanding of neurodevelopmental disorders.     

A New Link Between Insulin Signaling and Fragile X Syndrome

正Fragile X syndrome(FXS)is the most common cause of inherited intellectual disability and the most common known genetic cause of autism or autism spectrum disorders.FXS is caused by silencing or mutation of the fragile X mental retardation gene(FMR1),a known RNA-binding protein that acts as a negative regulator of translation[1,2].     

Role of the PTEN signaling pathway in autism spectrum disorder

Autism is an etiologically heterogeneous group of neurodevelopmental disorders,diagnosed mostly by the clinical behavioral phenotypes.The concept that the tumor-related gene PTEN plays a critical role in autism spectrum disorder has emerged over the last decade.In this review,we focus on the essential role of the PTEN signaling pathway in neuronal differentiation and the formation of neural circuitry,as well as genetic mouse models with Pten manipulations.Particularly,accumulated data suggest that the effect of PTEN on neural stem-cell development contributes significantly to the pathophysiology of autism spectrum disorders.     

Dysregulation of neurogenesis by neuroinflammation:key differences in neurodevelopmental and neurological disorders

Embryonic neurogenesis is the process of generating neurons, the functional units of the brain. Because of its sensitivity to adverse intrauterine environment such as infection, dysregulation of this process has emerged as a key mechanism underlying many neurodevelopmental disorders such as autism spectrum disorders (ASD). Adult neurogenesis, although is restricted to a few neurogenic niches, plays pivotal roles in brain plasticity and repair. Increasing evidence suggests that impairments in adult neurogenesis are in-volved in major neurodegenerative disorders such as Alzheimer's disease. A hallmark feature of these brain disorders is neuroinflammation, which can either promote or inhibit neurogenesis depending upon the context of brain microenvironment. In this review paper, we present evidence from both experimental and human studies to show a complex picture of relationship between these two events, and discussed potential factors contributing to different or even opposing actions of neuroinflammation on neurogenesis in neuro-developmental and neurological disorders.     

Towards the Framework of Understanding Autism Spectrum Disorders

<正>The prevalence of autism spectrum disorders (ASD) has been high worldwide, reaching 1/59 children in the United States as reported by the Centers of Disease Control and Prevention. Since genetic components play a major role in ASD [1], it is astonishing that the occurrence of ASD would be this high probabily due to genetic causes. It is worthy to note that autistic phenotypes of ASD patients     

Prevalence of autism spectrum disorders in China

Autism spectrum disorders （ASD） are a heterogeneous group of neuro-developmental disorders that are among the most genetically heritable behavioral disorders.[1] ASD have attracted increasing attention from researchers and public-health agencies worldwide, particularly in Western high-income nations, where substantial increases in the prevalence of ASD have been reported since the 1990s, and where strong advocacy by families of persons with autism has resulted in increased funding for research into the causes of these devastating conditions. Far fewer data on ASD prevalence are available from Asia than from Europe and North America. Thus, the report in the previous issue by Wan and colleagues,I2] of a comprehensive review and meta- analysis of prevalence estimates for ASD in mainland China, Taiwan, Hong Kong and Macau, is a welcome contribution to the international literature. The results of the study, which focused on analyses of populations 〈 18 years of age, highlight the urgent need for large methodologically rigorous studies of the prevalence of ASD in Han Chinese populations--an ethnic group that includes approximately 20% of the world＇s population.     

Brain effects of chronic IBD in areas abnormal in autism and treatment by single neuropeptides secretin and oxytocin

Recent research points to the connection between behavioral and gut disorders. Early adverse events are associated with inflammatory bowel disease (IBD). In animal models, maternal deprivation and social isolation predispose to gastric erosion and brain pathology. This study examined (1) brain effects of chronic gastrointestinal inflammation in a rat model of acquired IBD and (2) whether such changes are resolved by individual secretin (S) or oxytocin (OT) peptide treatment. Neurological manifestations of IBD were mapped by c-fos gene expression in male Sprague-Dawley rats (n=10) with trinitrobenzene sulfonic acid (TNBS)-induced IBD vs controls (n=11). IBD was characterized by moderate/severe infiltration of inflammatory cells 10 d after TNBS infusion. Age-matched pairs were processed for immunocytochemical detection of Fos, expressed when neurons are stimulated. S or OT (100 μg/250 μL saline) or equivolume saline was administered iv by Alzet pump for 20 d after disease onset. Degree of resolution of colitis-induced brain activation was assessed by c-fos expression, and mean numbers of Fos-immunoreactive nuclei for each group were compared using Independent Samples T-test. Chronic IBD activated periventricular gray, hypothalamic/visceral thalamic stress axes and cortical domains, and septal/preoptic/amygdala, brain areas abnormal in autism. Single peptide treatment with S or OT did not alter the effects of inflammation on the brain. Brain areas concomitantly activated by visceral inflammation are those often abnormal in autism, suggesting that IBD could be a model for testing treatments of autism. Other single and combined peptide treatments of IBD should be tested. The clinical implications for treating autism, IBD, and concomitant sickness behaviors with peptide therapy, with or without maternal nurturing as a natural equivalent, are presented.     

Self-healing hydrogel for tissue repair in the central nervous system

<正>Neurological disorders are diseases of the central and peripheral nervous systems.These disorders include Alzheimer’s disease,epilepsy,brain tumor,and cerebrovascular diseases(stroke,migraine and other headache disorders,multiple sclerosis,Parkinson’s disease,and neuroinfections).Hundreds of millions     

Using optogenetics to translate the “inflammatory dialogue” between heart and brain in the context of stress

Inflammatory processes are an integral part of the stress response and are likely to result from a programmed adaptation that is vital to the organism’s survival and well-being.The whole inflammatory response is mediated by largely overlapping circuits in the limbic forebrain,hypothalamus and brainstem,but is also under the control of the neuroendocrine and autonomic nervous systems.Genetically predisposed individuals who fail to tune the respective contributions of the two systems in accordance with stressor modality and intensity after adverse experiences can be at risk for stress-related psychiatric disorders and cardiovascular diseases.Altered glucocorticoid(GC) homeostasis due to GC resistance leads to the failure of neural and negative feedback regulation of the hypothalamic-pituitary-adrenal axis during chronic inflammation,and this might be the mechanism underlying the ensuing brain and heart diseases and the high prevalence of co-morbidity between the two systems.By the combined use of light and genetically-encoded lightsensitive proteins,optogenetics allows cell-type-specific,fast(millisecond-scale) control of precisely defined events in biological systems.This method is an important breakthrough to explore the causality between neural activity patterns and behavioral profiles relevant to anxiety,depression,autism and schizophrenia.Optogenetics also helps to understand the "inflammatory dialogue",the inflammatory processes in psychiatric disorders and cardiovascular diseases,shared by heart and brain in the context of stress.     

A Fiber Tractography Study of Social-Emotional Related Fiber Tracts in Children and Adolescents with Autism Spectrum Disorder

The symptoms of autism spectrum disorder(ASD) have been hypothesized to be caused by changes in brain connectivity. From the clinical perspective, the‘‘disconnectivity' hypothesis has been used to explain characteristic impairments in ‘‘socio-emotional' function.Therefore, in this study we compared the facial emotional recognition(FER) feature and the integrity of socialemotional-related white-matter tracts between children and adolescents with high-functioning ASD(HFA) and their typically developing(TD) counterparts. The correlation between the two factors was explored to find out if impairment of the white-matter tracts is the neural basis of social-emotional disorders. Compared with the TD group,FER was significantly impaired and the fractional anisotropy value of the right cingulate fasciculus was increased in the HFA group(P \ 0.01). In conclusion, the FER function of children and adolescents with HFA was impaired and the microstructure of the cingulate fasciculus had abnormalities.     

Special Topic on Mental Health and Addiction

<正>We are delighted to have been invited to edit this Special Topic on Mental Health and Addiction.Mental disorders like drug addiction,mood disorders,and schizophrenia affect a sizeable proportion of the human population,severely compromise the quality of life,and constitute a large global burden of disease.The evolution of molecular,cellular,and neurophysiological studies of rodents and the     

Adenylate cyclase activator forskolin alleviates intracerebroventricular propionic acid-induced mitochondrial dysfunction of autistic rats

Neuronal mitochondrial dysfunction increases inflammatory mediators and leads to free radical generation and anti-oxidant enzymatic alterations,which are major neuropathological hallmarks responsible for autism.Mitochondrial dysfunction in autism is associated with decreased ATP levels due to reduced levels of cyclic adenosine monophosphate.Rat models of autism were established by intracerebroventricular injection of propionic acid.These rat models had memory dysfunction,decreased muscle coordination and gait imbalance.Biochemical estimation of propionic acid-treated rats showed changes in enzyme activity in neuronal mitochondrial electron transport chain complexes and increases in pro-inflammatory cytokines,oxidative stress and lipid biomarkers.Oral administration of 10,20 and 30 mg/kg adenylate cyclase activator forskolin for 15 days reversed these changes in a dose-dependent manner.These findings suggest that forskolin can alleviate neuronal mitochondrial dysfunction and improve neurological symptoms of rats with autism.This study was approved by the RITS/IAEC,SIRSA,HARYANA on March 3,2014(approval No.RITS/IAEC/2014/03/03).     

INSTRUCTIONS TO AUTHORS

<正>GENERAL INFORMATION World Jour nal of Psychiatry(World J Psychiatr,WJP,online ISSN2220-3206,DOI:10.5498)is a peer-reviewed open access(OA)academic journal that aims to guide clinical practice and improve diagnostic and therapeutic skills of clinicians.Aim and scope WJP covers topics concerning behavior and behavior mechanisms,psychological phenomena and processes,mental disorders,behavioral disciplines and activities,adjustment disorders,anxiety disorders,delirium,dementia,amnestic disorders,cognitive disorders,     

Cognition and movement in neurodegenerative disorders:a dynamic duo

<正>People with neurodegenerative disorders often experience problems across a variety of functional domains,including cognition,movement,and psychosocial functioning.The classification of these disorders is based on the phenotypical manifestations that represent the most prominent clinical features.For example,Parkinson’s disease and Huntington’s disease are typically regarded as movement disorders,whereas Alzheimer’s disease(AD) and other dementias are regarded as cognitive disorders.     

Exploring pre-degenerative alterations in humans using induced pluripotent stem cell-derived dopaminergic neurons

<正>Understanding the cellular and molecular mechanisms underlying human neurological disorders is hindered by both the complexity of the disorders and the lack of suitable experimental models recapitulating key pathological features of the disease.This is a crucial issue since a limited understanding of pathogenic mechanisms precludes the development of drugs counteracting the progression of the disease.Among neurological disorders,Parkinson’s disease(PD)is likely caused by a variable     

P wave changes in patients with depression or anxiety disorder

Background and Objective: Activation of the sympathetic nervous system plays an important role in regulating cardiovascular actions. P wave parameters can provide general information on central cardiovascular autonomic regulatory responses, which are altered in patients with anxiety disorders and depression. Material and Methods: The P wave duration was measured in 71 consecutive patients with two different psychiatric diagnoses (depression and anxiety disorders) and in 50 physically and mentally healthy age- and gender-matched controls. The psychiatric diseases were diagnosed using DSM-IV and clinical review. The depression and anxiety levels were also scored using the Beck and Hamilton depression scales and the State-Trait Anxiety Inventory scale. Result: Both the maximum (Pmax) and minimum (Pmin) P wave duration were greater in the patients with psychiatric disorders than in the healthy controls; Pmax was significantly greater in patients with depression or anxiety disorders (p<0.01). Although Pmin of anxiety patients was longer than controls, the difference was non-significant between groups (Bonferroni test, p=0.02). The Beck depression results were positively correlated with Pmin and Pmax (p<0.01). Age was positively correlated with PWD, and this correlation was independent of the psychiatric disorders (p<0.05). Conclusion: Our results suggest that the psychiatric disorders are associated with increases in Pmax and Pmin. The changes were associated with the degree of depression and the presence of anxiety disorder.     

Psycho-cognitive behavioral problems in sleep disordered children

Sleep disturbances are common in childhood and adolescence. Sleep problems in early infants tend to be persistent and prominent in preschool and school-aged children. Chronic sleep disorders, especially in young children may lead to neurobehavioral problems and psycho-cognitive impairment. Sleep difficulties may be the result of underlying medical conditions, (breathing disorders) or psychological problems. Research studies have shown the association between sleep disorders and day time cognitive impairment, behavioral problems, poor school performance and inattention in children. Appropriate diagnosis and early management of sleep disorders in children lead to improvement of neurocognitive function and behavioral problems in these children.     

Genetics and epigenetics of circadian rhythms and their potential roles in neuropsychiatric disorders

Circadian rhythm alterations have been implicated in multiple neuropsychiatric disorders,particularly those of sleep,addiction,anxiety,and mood. Circadian rhythms are known to be maintained by a set of classic clock genes that form complex mutual and self-regulatory loops. While many other genes showing rhythmic expression have been identified by genome-wide studies,their roles in circadian regulation remain largely unknown. In attempts to directly connect circadian rhythms with neuropsychiatric disorders,genetic studies have identifi ed gene mutations associated with several rare sleep disorders or sleep-related traits. Other than that,genetic studies of circadian genes in psychiatric disorders have had limited success. As an important mediator of environmental factors and regulators of circadian rhythms,the epigenetic system may hold the key to the etiology or pathology of psychiatric disorders,their subtypes or endophenotypes. Epigenomic regulation of the circadian system and the related changes have not been thoroughly explored in the context of neuropsychiatric disorders. We argue for systematic investigation of the circadian system,particularly epigenetic regulation,and its involvement in neuropsychiatric disorders to improve our understanding of human behavior and disease etiology.