Aspects Of Autism Spectrum Disorder Research Articles

Induction of core symptoms of autism spectrum disorder by in vivo CRISPR/Cas9-based gene editing in the brain of adolescent rhesus monkeys

Although CRISPR/Cas9-mediated gene editing is widely applied to mimic human disorders, whether acute manipulation of disease-causing genes in the brain leads to behavioral abnormalities in non-human primates remains to be determined. Here we induced genetic mutations in MECP2, a critical gene linked to Rett syndrome (RTT) and autism spectrum disorders (ASD), in the hippocampus (DG and CA1–4) of adolescent rhesus monkeys (Macaca mulatta) in vivo via adeno-associated virus (AAV)-delivered Staphylococcus aureus Cas9 with small guide RNAs (sgRNAs) targeting MECP2. In comparison to monkeys injected with AAV-SaCas9 alone (n = 4), numerous autistic-like behavioral abnormalities were identified in the AAV-SaCas9-sgMECP2-injected monkeys (n = 7), including social interaction deficits, abnormal sleep patterns, insensitivity to aversive stimuli, abnormal hand motions, and defective social reward behaviors. Furthermore, some aspects of ASD and RTT, such as stereotypic behaviors, did not appear in the MECP2 gene-edited monkeys, suggesting that different brain areas likely contribute to distinct ASD symptoms. This study showed that acute manipulation of disease-causing genes via in vivo gene editing directly led to behavioral changes in adolescent primates, paving the way for the rapid generation of genetically engineered non-human primate models for neurobiological studies and therapeutic development.

Epidemiological, clinical and psychometric aspects of Autism spectrum disorder among children in Zagazig University hospital

Background:Autism spectrum disorder (ASD) is a severe psychiatric disorder of childhood comprised severe troubles in verbal, non verbal communication, language development, repetitive limited patterns of behaviors and obsessive resistance to small changes in familiar surrounding. Aim to assess role of epidemiological, clinical and psychiatric determinants as risk factors of ASD. Methods: A case control study was recruited on 72 ASD children attending psychiatric outpatient clinic and 72 healthy children. Their caregivers completed a questionnaire about risk factors for ASD. Then they underwent complete assessment of mental age using Stanford-Binet intelligence scale, childhood autism rating scale to outline severity of ASD in cases and exclude presence of autistic features in controls.Results:There is a statistically significant difference between both groups regarding mother,and father education, fathers’ age at conception, family history of psychiatric disorders, history of induction of ovulation, hypertension during pregnancy, folic acid supplementation during 1st trimester of pregnancy, use of anti D, history of postnatal hypoxia, admission to NICU and feeding type. A significant difference between them concerning reaction to others and delayed developmental milestones was found. About 63% and 58% had severe autism and mild to severe mental retardation respectivey. Paternal age, positive family history of psychiatric diseases, postnatal hypoxia significantly increased risk of ASD. Folic acid supplementation during 1st trimester of pregnancy significantly decreased risk.Conclusion: Family history of psychiatric disorders, Advanced fathers’ age at conception, postnatal hypoxia were significant risk factors. Folic acid supplementation during 1st trimester is a significant protector

Psychological aspects of autism spectrum disorder

Introduction: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that occurs within the first 3 years of life, which is characterised by poor social skills, communication problems and stereotyped patterns of behaviour. Autism is a life-long disorder that has a substantial effect on the individual, their family, and society. The purpose of this paper is to provide an overview about the psychosocial aspects of autism spectrum disorders. Methods: An analysis of relevant literature, sources from the internet and published literature, personal experience and observations of the author. Findings: Despite widespread research and greater public awareness, ASD has an unclear etiology and no known cure, making it difficult to acquire an accurate and timely diagnosis. Psychologic functions such as attention, executive function, academic functioning, memory, emotions, and sensory processing are described. There is a need for continuous psycho-social support for people with ASD and their relatives during the diagnostics and early intervention period, as well as resources that better represent the diversity of experiences and symptoms associated with ASD across the lifespan. Conclusion: It is clear that more special education services are needed, together with timely and ongoing psychosocial support to parents of children with ASD.

The Autism Treatment Network: Bringing Best Practices to All Children With Autism.

The Autism Treatment Network and Autism Intervention Research Network on Physical Health were established in 2008 with goals of improving understanding of the medical aspects of autism spectrum disorders. Over the past decade, the combined network has conducted >2 dozen clinical studies, established clinical pathways for best practice, developed tool kits for professionals and families to support better care, and disseminated these works through numerous presentations at scientific meetings and publications in medical journals. As the joint network enters its second decade continuing this work, it is undergoing a transformation to increase these activities and accelerate their incorporation into clinical care at the primary care and specialty care levels. In this article, we describe the past accomplishments and present activities. We also outline planned undertakings such as the establishment of the Autism Learning Health Network, the increasing role of family members as co-producers of the work of the network, the growth of clinical trials activities with funding from foundations and industry, and expansion of work with primary care practices and autism specialty centers. We also discuss the challenges of supporting network activities and potential solutions to sustain the network.

Myocyte Enhancer Factor 2A (MEF2A) Defines Oxytocin-Induced Morphological Effects and Regulates Mitochondrial Function in Neurons.

The neuropeptide oxytocin (OT) is a well-described modulator of socio-emotional traits, such as anxiety, stress, social behavior, and pair bonding. However, when dysregulated, it is associated with adverse psychiatric traits, such as various aspects of autism spectrum disorder (ASD). In this study, we identify the transcription factor myocyte enhancer factor 2A (MEF2A) as the common link between OT and cellular changes symptomatic for ASD, encompassing neuronal morphology, connectivity, and mitochondrial function. We provide evidence for MEF2A as the decisive factor defining the cellular response to OT: while OT induces neurite retraction in MEF2A expressing neurons, OT causes neurite outgrowth in absence of MEF2A. A CRISPR-Cas-mediated knockout of MEF2A and retransfection of an active version or permanently inactive mutant, respectively, validated our findings. We also identified the phosphatase calcineurin as the main upstream regulator of OT-induced MEF2A signaling. Further, MEF2A signaling dampens mitochondrial functioning in neurons, as MEF2A knockout cells show increased maximal cellular respiration, spare respiratory capacity, and total cellular ATP. In summary, we reveal a central role for OT-induced MEF2A activity as major regulator of cellular morphology as well as neuronal connectivity and mitochondrial functioning, with broad implications for a potential treatment of disorders based on morphological alterations or mitochondrial dysfunction.

A realist evaluation of peer mentoring support for university students with autism

Education is effective in improving outcomes in autism spectrum disorder (ASD). While peer mentoring has demonstrated preliminary promise in supporting university students with ASD, the effective mechanisms remain unclear. The aims of this study were to explore the required contexts, mechanisms and outcomes of peer mentoring for university students with ASD. Semi‐structured interviews based on a Realist Evaluation framework were conducted with 23 peer mentors and 24 university students with ASD. Thematic analysis identified three context themes: ‘environmental conditions’, ‘university course demands’ and ‘aspects of ASD’; four mechanism themes: ‘mentor’, ‘communication and social interaction’, ‘problem solving’ and ‘training and supervision’; and five outcome themes: ‘identifying personal strengths’, ‘increased autonomy’, ‘achieving goals’, ‘relationships’ and ‘positive mentor outcomes’. Standard peer mentoring approaches can be enhanced to meet the needs of students with ASD by including training for mentors on ASD, and approaches that support mentees’ social interaction and communication needs.

Autism Spectrum Disorder and International Travel

The literature on international travellers with psychiatric disorders is limited. This perspective article highlights various travel-related aspects of autism spectrum disorder (ASD), including its aetiological association with maternal migration, the difficulties faced by longterm travelers with autistic children, and the facilitation of international travel for autistic individuals by the travel industry. Depending on the severity of their condition, autistic individuals may find specific aspects of the travel experience particularly distressing. Travel medicine practitioners should be aware of the unique needs of autistic travelers when providing pre-travel health counseling. There is also an onus on the travel industry to facilitate safe and enjoyable travel and remove barriers faced by autistic travellers.

Dificuldades de mães e de pais no relacionamento com crianças com Transtorno do Espectro Autista

The characteristic impairments of the Autism Spectrum Disorder (ASD) may lead children to present limitations in their development, maintenance, and understanding of socio-affective relationships. Therefore, this study investigated the difficulties reported by mothers and fathers in the relationship with their children at risk of ASD or diagnosed with ASD. The participants were eight mothers and eight parents of children at risk of ASD or diagnosed with ASD by means of responding to a semi-structured interview script. From the parents’ report, it was possible to identify that, for most of them, the main difficulty in the relationship with their children was due to the impairments in interactive communication present in the children with risk/diagnosis of ASD. Besides, the parent-child bond built through daily care activities or through playful activities allows the occurrence of behaviors sometimes compromised in ASD. Thus, it is necessary to invest in the bonds with children at risk or diagnosis of this disorder, since they are responsible for the development of compromised aspects of ASD, such as shared attention responsible for the development of interactive communication. Keywords: Autism Spectrum Disorder, mother-child relationship, father- child relationship.

2091 Neurophysiological substrates and developmental sequelae of sensory differences in infants at high risk for autism spectrum disorder

OBJECTIVES/SPECIFIC AIMS: Background: Children with autism spectrum disorder (ASD) show a broad range of unusual responses to sensory stimuli and experiences. It has been hypothesized that early differences in sensory responsiveness arise from atypical neural function and produce “cascading effects” on development across a number of domains, impacting social and communication skill, as well as broader development in children affected by ASD. A primary challenge to confirming these hypotheses is that ASD cannot be definitely diagnosed in the earliest stages of development (i.e., infancy). A potential solution is to prospectively follow infants at heightened risk for ASD based on their status as infant siblings of children who are diagnosed. We examined the developmental sequelae and possible neurophysiological substrates of three different patterns of sensory responsiveness—hyporesponsiveness (reduced or absent responding to sensory stimuli) and hyperresponsiveness (exaggerated responding to sensory stimuli), as well as sensory seeking (craving of or fascination with certain sensory experiences). Infants at high risk (HR) for ASD were compared with a control group of infants at relatively lower risk for ASD (LR; siblings of children with typical developmental histories). Objectives: Research questions included: (a) Do HR infants differ from LR infants in early sensory responsiveness?, (b) Does sensory responsiveness predict future ASD and related symptomatology? and (c) Is sensory responsiveness predicted by resting brain states? METHODS/STUDY POPULATION: Methods: To answer these questions, we carried out a longitudinal correlational investigation in which 20 HR infants and 20 LR controls matched on sex and chronological age were followed over 18 months. At entry to the study, when infants were 18 months old, sensory responsiveness was measured using the Sensory Processing Assessment and the Sensory Experiences Questionnaire, and a number of putative neural signatures of early sensory differences were measured via resting state EEG. When infants were 24 and 36 months of age, ASD and related symptomatology was evaluated in a comprehensive diagnostic evaluation. RESULTS/ANTICIPATED RESULTS: Results: HR infants trended towards increased hyporesponsiveness and hyperresponsiveness and showed significantly elevated levels of sensory seeking relative to LR controls at 18 months of age. Both groups, furthermore, displayed a high degree of heterogeneity in sensory responsiveness. Atypical sensory responsiveness (increased hyperresponsiveness and/or hyporesponsiveness, as well as sensory seeking behavior) predicted several aspects of ASD and related symptomatology, including social, communication, and play skill, and was associated with differences in resting brain state, including metrics of oscillatory power, complexity, and connectivity, as well as hemispheric asymmetry. Moderation analyses revealed that several relations varied according to risk group, such that associations were stronger in magnitude in the HR Versus LR group. DISCUSSION/SIGNIFICANCE OF IMPACT: Conclusion: Findings provide empirical support for the notion that early sensory responsiveness may produce cascading effects on development in infants at heightened risk for ASD. Differences in resting brain states may underlie atypical behavioral patterns of sensory responsiveness. From a clinical standpoint, results suggest that early sensory differences may be useful for predicting developmental trajectories, and be potentially important targets for early preventive intervention, in infants at risk for autism.

Structural Covariance of Sensory Networks, the Cerebellum, and Amygdala in Autism Spectrum Disorder.

Sensory dysfunction is a core symptom of autism spectrum disorder (ASD), and abnormalities with sensory responsivity and processing can be extremely debilitating to ASD patients and their families. However, relatively little is known about the underlying neuroanatomical and neurophysiological factors that lead to sensory abnormalities in ASD. Investigation into these aspects of ASD could lead to significant advancements in our general knowledge about ASD, as well as provide targets for treatment and inform diagnostic procedures. Thus, the current study aimed to measure the covariation of volumes of brain structures (i.e., structural magnetic resonance imaging) that may be involved in abnormal sensory processing, in order to infer connectivity of these brain regions. Specifically, we quantified the structural covariation of sensory-related cerebral cortical structures, in addition to the cerebellum and amygdala by computing partial correlations between the structural volumes of these structures. These analyses were performed in participants with ASD (n = 36), as well as typically developing peers (n = 32). Results showed decreased structural covariation between sensory-related cortical structures, especially between the left and right cerebral hemispheres, in participants with ASD. In contrast, these same participants presented with increased structural covariation of structures in the right cerebral hemisphere. Additionally, sensory-related cerebral structures exhibited decreased structural covariation with functionally identified cerebellar networks. Also, the left amygdala showed significantly increased structural covariation with cerebral structures related to visual processing. Taken together, these results may suggest several patterns of altered connectivity both within and between cerebral cortices and other brain structures that may be related to sensory processing.

Neuroligin 3 R451C mutation alters electroencephalography spectral activity in an animal model of autism spectrum disorders

Human studies demonstrate that sleep impairment is a concurrent comorbidity of autism spectrum disorders (ASD), but its etiology remains largely uncertain. One of the prominent theories of ASD suggests that an imbalance in synaptic excitation/inhibition may contribute to various aspects of ASD, including sleep impairments. Following the identification of Nlgn3R451C mutation in patients with ASD, its effects on synaptic transmission and social behaviours have been examined extensively in the mouse model. However, the contributory role of this mutation to sleep impairments in ASD remains unknown. In this study, we showed that Nlgn3R451C knock-in mice, an established genetic model for ASD, exhibited normal duration and distribution of sleep/wake states but significantly altered electroencephalography (EEG) power spectral profiles for wake and sleep.

The association between parents’ ratings of ASD symptoms and anxiety in a sample of high-functioning boys and adolescents with Autism Spectrum Disorder

BackgroundThe relationship between symptoms of Autism Spectrum Disorder (ASD) and Generalised Anxiety Disorder (GAD) is complex and sometimes confounding. However, exploration of that relationship has significant potential to assist in treatment or avoidance of GAD by identifying ASD-related behaviours as ‘targets’ for intervention with anxious children as well as for preventative treatments that could be implemented into daily routines before children become anxious. To further understanding of this relationship, the association between parent-ratings of their sons’ ASD symptoms and GAD symptoms was investigated in two samples of boys with high-functioning ASD. MethodsParents of a sample of 90 pre-adolescent (M age=8.8yr) and 60 adolescent males (M age=14.6yr) completed the Social Responsiveness Scale (SRS) and the GAD subscale of the Child and Adolescent Symptom Inventory (CASI-4 GAD) about their sons. ResultsPre-adolescents had significantly higher SRS scale scores than adolescents. For pre-adolescents, high levels of tension in social situations were associated with 3.5-times greater likelihood of having GAD; for adolescents, experiencing difficulty in changes in routine was associated with a 10-fold increase in risk of GAD. ConclusionsIn addition to focussing upon GAD itself, preventative and treatment options aimed at reducing GAD or its risk might profitably recognise and focus upon these two aspects of ASD that are different across the two age groups but each of which was significantly associated with GAD severity and prevalence in this study.

Is My Son Autistic?

Is My Son Autistic?

Hyperactivity and lack of social discrimination in the adolescent Fmr1 knockout mouse.

The aims of this study were to investigate behaviour relevant to human autism spectrum disorder (ASD) and the fragile X syndrome in adolescent Fmr1 knockout (KO) mice and to evaluate the tissue levels of striatal monoamines. Fmr1 KO mice were evaluated in the open field, marble burying and three-chamber test for the presence of hyperactivity, anxiety, repetitive behaviour, sociability and observation of social novelty compared with wild-type (WT) mice. The Fmr1 KO mice expressed anxiety and hyperactivity in the open field compared with WT mice. This increased level of hyperactivity was confirmed in the three-chamber test. Fmr1 KO mice spent more time with stranger mice compared with the WT. However, after a correction for hyperactivity, their apparent increase in sociability became identical to that of the WT. Furthermore, the Fmr1 KO mice could not differentiate between a familiar or a novel mouse. Monoamines were measured by HPLC: Fmr1 KO mice showed an increase in the striatal dopamine level. We conclude that the fragile X syndrome model seems to be useful for understanding certain aspects of ASD and may have translational interest for studies of social behaviour when hyperactivity coexists in ASD patients.

Autism spectrum disorder, attention-deficit hyperactivity disorder and offending

Purpose – A wealth of research on autism spectrum disorders (ASD) and attention-deficit hyperactivity disorder (ADHD) has led to increased understanding and identification of each of these developmental disorders. Existing literature has sparked controversial discussions regarding whether aspects of ASD and ADHD predispose individuals to criminality. The purpose of this paper is to explore the link between these conditions and offending. Design/methodology/approach – A review of the literature on ASD, ADHD and offending was undertaken. This paper looks at the particular focus of the literature on the involvement of individuals with ADHD and ASD within the criminal justice system. Findings – There is some evidence of a link between ADHD and criminality. However, the relationship between ASD and offending is a little more difficult to ascertain. Complicating this further is the relatively unexplored subject of comorbid ASD/ADHD and criminal behaviour. This paper found that additional cognitive deficits and conduct problems are associated with comorbid ASD/ADHD, highlighting the need for further research and development of interventions. Originality/value – This paper seeks to examine whether predictions can be made with regards to what offending behaviour may look like in an individual with comorbid ASD/ADHD. This paper reviews the literature on offending in relation to both disorders to examine whether predictions can be made with regards to what the offending behaviour of an individual with ASD and ADHD may look like.

Recognition of Autism Spectrum Disorder (ASD) symptoms and knowledge about some other aspects of ASD among final year medical students in Nigeria, Sub-Saharan Africa.

Background Earlier studies suggest that knowledge about Autism Spectrum Disorder (ASD) among healthcare workers in Nigeria is low. This present study assessed the knowledge of Nigerian final year medical students about symptoms of ASD and some other aspects of ASD. This is a cross sectional descriptive study that drew a total of seven hundred and fifty-seven (757) final year medical students from ten (10) randomly selected fully accredited medical schools out of a total of twenty-seven (27) fully accredited medical schools in Nigeria. Sociodemographic and Knowledge about Childhood Autism among Health Workers (KCAHW) questionnaires were used to assess knowledge of final year medical students about ASD and obtain demographic information.ResultsOnly few, 218 (28.8 %) of the 757 final year medical students had seen and participated in evaluation and management of at least a child with ASD during their clinical postings in pediatrics and psychiatry. Knowledge and recognition of symptoms of ASD is observed to be better among this group of final year medical students as shown by higher mean scores in the four domains of KCAHW questionnaire. Knowledge about ASD varies across gender and regions. Misconceptions about ASD were also observed among the final year medical students.ConclusionsMore focus needs to be given to ASD in the curriculum of Nigerian undergraduate medical students, especially during their psychiatry and pediatric clinical postings.Electronic supplementary materialThe online version of this article (doi:10.1186/s13104-015-1433-0) contains supplementary material, which is available to authorized users.

Genetics and genomics of autism spectrum disorder: embracing complexity.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder (NDD) characterized by impairments in social communication and social interaction and the presence of repetitive behaviors and/or restricted interests. ASD has profound etiological and clinical heterogeneity, which has impeded the identification of risk factors and pathophysiological processes underlying the disorder. A constellation of (i) types of genetic variation, (ii) modes of inheritance and (iii) specific genomic loci and genes have all recently been implicated in ASD risk, and these findings are currently being extended with functional analyses in model organisms and genotype-phenotype correlation studies. The overlap of risk loci between ASD and other NDDs raises intriguing questions around the mechanisms of risk. In this review, we will touch upon these aspects of ASD and how they might be addressed.

Trans-synaptic zinc mobilization improves social interaction in two mouse models of autism through NMDAR activation.

Genetic aspects of autism spectrum disorders (ASDs) have recently been extensively explored, but environmental influences that affect ASDs have received considerably less attention. Zinc (Zn) is a nutritional factor implicated in ASDs, but evidence for a strong association and linking mechanism is largely lacking. Here we report that trans-synaptic Zn mobilization rapidly rescues social interaction in two independent mouse models of ASD. In mice lacking Shank2, an excitatory postsynaptic scaffolding protein, postsynaptic Zn elevation induced by clioquinol (a Zn chelator and ionophore) improves social interaction. Postsynaptic Zn is mainly derived from presynaptic pools and activates NMDA receptors (NMDARs) through postsynaptic activation of the tyrosine kinase Src. Clioquinol also improves social interaction in mice haploinsufficient for the transcription factor Tbr1, which accompanies NMDAR activation in the amygdala. These results suggest that trans-synaptic Zn mobilization induced by clioquinol rescues social deficits in mouse models of ASD through postsynaptic Src and NMDAR activation.

Aspectos genéticos y neuroendocrinos en el trastorno del espectro autista

The autism spectrum disorder (ASD) was described in 1943 and is defined as a developmental disorder that affects social interaction and communication. It is usually identified in early stages of development from 18 months of age. Currently, autism is considered a neurological disorder with a spectrum covering cases of different degrees, which is associated with genetic factors, not genetic and environmental. Among the genetic factors, various syndromes have been described that are associated with this disorder. Also, the neurobiology of autism has been studied at the genetic, neurophysiological, neurochemical and neuropathological levels. Neuroimaging techniques have shown multiple structural abnormalities in these patients. There have also been changes in the serotonergic, GABAergic, catecholaminergic and cholinergic systems related to this disorder. This paper presents an update of the information presented in the genetic and neuroendocrine aspects of autism spectrum disorder.

Early screening for autism spectrum disorder in Serbia: A pilot study of screening instruments for parents and child care workers

Introduction: Early diagnosis of autism spectrum disorder (ASD) can lead to early interventions, which may improve developmental and academic outcomes in children with ASD. Early screening is thus of significant importance. Aims: This study had two aims. First, it was aimed to translate into Serbian five screening instruments for ASD: Modified Checklist for Autism in Toddlers - Revised, (M-CHATR), Quantitative Checklist for Autism in Toddlers (Q-CHAT), Infant-Toddler Checklist (ITC), and Early Screening Autistic Traits Questionnaire (ESAT) for parents and the Checklist for Early Signs of Developmental Disorders (CESDD) for child care workers. Second, it was aimed to test the feasibility of the included data from parents and child care workers in early ASD screening. Methods: The translation and cultural adaptation process included standardized forward and backward translation with pilot testing. For screening within a childcare setting, one day-care center was selected. Data from at least one parent and a child care worker were collected for 47 children aged 28.94 months on average (SD = 8.39). Results: The face and content validity of each version of the instruments is satisfactory. The correlations among the scores showed that the ESET, M-CHAT-R, Q-CHAT, and ITC evaluate slightly different aspects of ASD. The M-CHAT covers similar aspects to the CESDD. Eight (17%) children were positively screened for ASD with at least one instrument. All positively screened with the ESAT, QCHAT, or ITC were also positive with the CESDD, while not all positively screened with M-CHAT-R were detected with the CESDD. All five instruments were able to detect the child with confirmed ASD in the final stage - clinical assessment. Conclusions: All five screening instruments are targeting ASD symptoms at early stage of life in our population. It is feasible to include reports from parents and child care workers in early ASD screening and there is an added value of combining data from the two.