Autism as a Disorder of Affective Empathy.

Since the first description by Leo Kanner, individuals with autism spectrum disorder (ASD) have been attributed a reduced empathy. However, it has not yet been clarified how empathy is specifically impaired in autism. Typically, scholars distinguish between the affective and the cognitive dimensions of empathy. The latter largely overlaps with the concept of the theory of mind (ToM), according to which we need internal inferences or simulations for gaining access to the hidden mental states of others. Since a deficit in ToM is a widely accepted explanation for difficulties of individuals with ASD in social interactions, limitations in cognitive empathy are accordingly assumed. Regarding affective empathy, there are contradictory results using various methods, showing an impaired affective empathy. The main aim of the paper is to present ASD primarily as a disorder of shared interpersonal and interaffective experiences and thus of affective empathy by means of a phenomenological analysis considering empirical studies. In this framework, a deficit of the ToM is accepted but criticized as a central explanatory approach for ASD since (1) it assumes a fundamental inaccessibility of other people, which does not correspond to our everyday social situations, and (2) it manifests developmentally long after the first signs of ASD, which means that its deficit cannot explain the basic autistic difficulties in social interactions.

Mothers' satisfaction with emergency care when their child has an autism spectrum disorder.

PURPOSE: This study aimed to examine factors identified by mothers as affecting their satisfaction with the care provided to their children in the Emergency Department (ED), among mothers of children with autistic spectrum disorder (ASD) in comparison to mothers of children without ASD. DESIGN AND METHODS: In this correlational quantitative study, 128 Israeli mothers - 59 (46%) mothers of children with ASD and 69 (54%) of children without ASD - completed an online survey based on a Ministry of Health national survey of patient experience. RESULTS: Mothers of children with ASD expressed lower satisfaction with the care provided. The difference was particularly evident concerning waiting times for examination of the child by nurses and physicians in the ED, whether the nurses were attentive and responsive to the mother's questions and concerns, whether the ED staff demonstrated coordination and cooperation with regard to medical care of the child, and whether work in the ED was conducted in an orderly and organized manner. The presence of communication difficulties in children predicted mothers' satisfaction with care. CONCLUSIONS: These findings suggest that certain needs of mothers and/or their children with ASD do not receive an appropriate response in the ED. PRACTICE IMPLICATIONS: It is important to raise the awareness of healthcare providers in EDs regarding the needs of children with ASD and their parents, especially children with communication difficulties. Strategies should be implemented to improve the experience of children with ASD and their parents in the ED.

Disparity in the dental care of children and adolescents with autism spectrum disorder in Korea: a national population-based cross-sectional study.

Individuals with autism spectrum disorders (ASD) have difficulty accessing dental care. We aim to verify whether individuals with ASD are properly managed by checking the frequency of dental visits, cost and severity of dental treatment compared with those without ASD. This cross-sectional study used the Korean Health Insurance Database to analyze the frequency, cost and severity of dental treatment in 209,780 people under the age of 19 with or without ASD in 2020. The average frequency of dental visits for individuals without ASD was 2.98 times, which was significantly higher (p < 0.001) than the 2.89 times for those with ASD. However, the average dental cost for individuals with ASD was USD 132.63, which was significantly higher (p < 0.001) than USD 116.57 for those without ASD. Additionally, the average number of times that individuals without ASD received severe dental treatment was 1.23 times, significantly higher than the 1.15 times for those with ASD. Further, per 10,000 people, we found that trauma treatment was recorded for an average of 21.90 individuals with ASD, significantly higher than the 7.75 recorded for those without ASD (p < 0.001). Individuals with ASD encounter significant disparities in accessing dental care, as evidenced by their relatively infrequent dental visits. This discrepancy can be attributed to various barriers including the financial burden compared with those without ASD.

Chronic Ambient Ozone Exposure Aggravates Autism-Like Symptoms in a Susceptible Mouse Model.

Although there is evidence that exposure to ground-level ozone (O3) may cause an increased risk of neurological disorders (e.g., autistic spectrum disorder), low-dose chronic ozone exposure and its adverse effects on the nervous system have not been fully understood. Here, we evaluated the potential neurotoxic effects of long-term exposure to environmentally relevant O3 concentration (200 µg/m3 via a whole-body inhalation system, 12 h/day for 5 days/week) using a susceptible mouse model of autism induced by valproic acid. Various indicators of oxidative stress, mitochondria, and synapse in the brain tissues were then measured to determine the overall damage of O3 to the mouse brain. The results showed an aggravated risk of autism in mice offspring, which was embodied in decreased antioxidant contents, disturbed energy generation in mitochondria, as well as reduced expressions of protein kinase Mζ (PKMζ) and synaptic proteins [e.g., Synapsin 1 (SYN 1), postsynaptic density protein-95 (PSD-95)]. Overall, our study indicates that prenatal exposure to environmentally relevant O3 may exacerbate the symptoms of autism, shedding light on possible molecular mechanisms and providing valuable insights into the pathogenesis of autism, especially concerning low-dose levels of those pollutants.

Understanding the Adoption of Dietary Interventions Within a Chinese Autism Online Community: A Diffusion of Innovations Perspective.

Dietary interventions are common but controversial treatments for autistic people. This study aims to understand the adoption of dietary interventions based on diffusion of innovations theory in the autism online community from four aspects: popularity, adoption process, the influence of opinion leaders, and post-adoption feedback. Our data was extracted from a Chinese autism community named Baidu Tieba autism forum. We applied a mixed-method including four analytical approaches: descriptive statistics for popularity analysis; machine learning models for automatic data classification and topic detection; social network analysis for exploring the influence of opinion leaders on the adoption phase; content analysis for revealing the family caregiver-reported feedback after adoption. Dietary interventions have become increasingly popular in the autism online community since 2018. Analysis of the adoption process revealed that family caregivers at different stages of adoption focused on different topics, and the number of interactions with opinion leaders had a significant effect on the highest level (p < .001) and stage span (p < .001) of health information adoption. According to findings from the feedback of family caregivers, the effects of dietary interventions varied from individuals with autism. Our study revealed the diffusion of unproven interventions, which is of great significance in promoting evidence-based practices.

Associations between neonatal jaundice and autism spectrum disorder or attention deficit hyperactivity disorder: Nationwide population based cohort study.

BACKGROUND/PURPOSE: Neonatal jaundice might result brain insults. Both autistic spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are developmental disorders, which might result from early brain injury at neonatal period. We aimed to explore the association between neonatal jaundice treated with phototherapy and the ASD or ADHD. METHODS: This retrospective nationwide population cohort study was based on a nationally representative database of Taiwan, and neonates born from 2004 to 2010 were enrolled. All eligible infants were divided into 4 groups, without jaundice, jaundice with no treatment, jaundice with simple phototherapy only and jaundice with intensive phototherapy or blood exchange transfusion (BET). Each infant was follow-up until the date of incident primary outcomes, death, or 7-year-old, whichever occurred first. Primary outcomes were ASD, ADHD. Using cox proportional hazard model to analyze their associations. RESULTS: In total, 118,222 infants with neonatal jaundice were enrolled, including diagnosed only (7260), simple phototherapy (82,990), intensive phototherapy or BET (27,972 infants). The cumulative incidences of ASD in each group was 0.57%, 0.81%, 0.77%, and 0.83%, respectively. The cumulative incidences of ADHD in each group was 2.83%, 4.04%, 3.52% and 3.48%, respectively. Jaundice groups were significantly associated with ASD, ADHD, or either one, even after all other extraneous maternal and neonatal variables were adjusted. After stratification, the associations were still existed in subgroup with birth weights ≥2500 grams and in male subgroup. CONCLUSION: Neonatal jaundice correlated with the ASD and ADHD. The associations were significant in infants of both sexes and with birth weights larger than 2500 grams.

Aberrant brain functional and structural developments in MECP2 duplication rats.

Transgenic animal models with homologous etiology provide a promising way to pursue the neurobiological substrates of the behavioral deficits in autism spectrum disorder (ASD). Gain-of-function mutations of MECP2 cause MECP2 duplication syndrome, a severe neurological disorder with core symptoms of ASD. However, abnormal brain developments underlying the autistic-like behavioral deficits of MECP2 duplication syndrome are rarely investigated. To this end, a human MECP2 duplication (MECP2-DP) rat model was created by the bacterial artificial chromosome transgenic method. Functional and structural magnetic resonance imaging (MRI) with high-field were performed on 16 male MECP2-DP rats and 15 male wildtype rats at postnatal 28 days, 42 days, and 56 days old. Multimodal fusion analyses guided by locomotor-relevant metrics and social novelty time separately were applied to identify abnormal brain networks associated with diverse behavioral deficits induced by MECP2 duplication. Aberrant functional developments of a core network primarily composed of the dorsal medial prefrontal cortex (dmPFC) and retrosplenial cortex (RSP) were detected to associate with diverse behavioral phenotypes in MECP2-DP rats. Altered developments of gray matter volume were detected in the hippocampus and thalamus. We conclude that gain-of-function mutations of MECP2 induce aberrant functional activities in the default-mode-like network and aberrant volumetric changes in the brain, resulting in autistic-like behavioral deficits. Our results gain critical insights into the biomarker of MECP2 duplication syndrome and the neurobiological underpinnings of the behavioral deficits in ASD.

Use of selective serotonin and norepinephrine reuptake inhibitors (SNRIs) in the treatment of autism spectrum disorder (ASD), comorbid psychiatric disorders and ASD-associated symptoms: a clinical review.

It is challenging to treat symptoms of autism spectrum disorder (ASD), comorbid psychiatric disorders and ASD-associated symptoms. Some of the commonly used medications to treat these can, and frequently do have serious adverse side effects. Therefore, it is important to identify medications that are effective and with fewer side effects and negative outcomes. In this review, we looked at current evidence available for using the serotonin and norepinephrine reuptake inhibitors (SNRIs) class of medications in treating some of these often difficult to treat symptoms and behaviors. An extensive literature search was conducted using EBSCO.host. Our search algorithm identified 130 articles, 6 of which were deemed to meet criteria for the purpose of this review. Each of these six articles was independently reviewed and critically appraised. As a prototype of the SNRIs family, venlafaxine was found to be a useful adjuvant in children and adults with ASD for the treatment of self-injurious behaviors, aggression, and ADHD symptoms when used in doses lower than its antidepressant dosage. However, duloxetine was not found to show any added benefit in treatment of any of the comorbid symptoms and behaviors in ASD when compared to other antidepressants. On the other hand, milnacipran was reported to produce improvements in impulsivity, hyperactivity symptoms, and social functioning through reduction of inattention of ADHD when comorbid with ASD. Overall, SNRIs were shown variable effectiveness in treatment of these comorbid symptoms and behaviors in ASD.

Non-specific effect of omega-3 fatty acid supplementation on autistic spectrum disorder: systematic review and meta-analysis.

METHODS: We searched seven databases and found 13 eligible controlled trials that use omega-3 supplementation in children and adolescents with ASD.Data extraction: We collected details on study design, intervention time, supplement dosage, and the autism assessment scale. Meta-analyses and subgroup analysis were conducted according to the autism symptoms. RESULTS: Omega-3 and omega-6 supplementation improved ASD symptoms according to the Aberrant Behavior Checklist (standard mean difference - SMD = -0.13; CI 95% = -0.34, -0.02). However, using subgroup analysis, we observed no efficacy in terms of improvements in hyperactivity (SMD = -0.03; CI 95%: -0.43, 0.36), irritability (SMD = -0.18; CI 95%: -0.51, 0.15), stereotypy (SMD = -0.03; CI 95%: -0.43, 0.36), inappropriate speech (SMD = -0.68; CI 95%: -1.49, 0.14), lethargy (SMD = -0.22; CI 95%: -0.58, 0.14), and social function (SMD = -0.71; IC 95%: -1.56, 0.14). W-3 and w-6 supplementation also showed no efficacy according to the Social Responsiveness Scale (SMD = 0.08; CI 95%: -0.23, 0.39). The adverse effects were classified as mild and equally distributed between the placebo and intervention groups. CONCLUSIONS: Despite w-3 and w-6 supplementation showing minimal beneficial effects in the treatment of autism, the subgroup analyses indicated that there is a lack of evidence on the beneficial role of w-3 and w-6 in treating ASD.Systematic Review Registration: PROSPERO number CRD42020146116.

Could Fetuin-A Be a Biomarker for Autism Spectrum Disorder and Cognitive Developmental Delay?

Early detection of cognitive developmental delay (CDD) and autism spectrum disorder (ASD) is challenging, despite the numerous scientific studies conducted and different therapeutic strategies. Lack of a biomarker for autism is a limiting factor for early diagnosis, which could provide better outcome with early start of therapy. Because of the high serum fetuin-A concentration during intrauterine life, it has been suggested that fetuin-A may have a role in brain development. The current study sought to determine if fetuin-A, a multifunctional glycoprotein thought to have a role in brain development, may be used as a biomarker for the diagnosis of ASD and developmental delay. The study involved 55 children with cognitive developmental delays and 40 healthy children. Two categories of children with cognitive developmental delays were identified. The participants were subjected to a psychiatric assessment as well as developmental testing. Only 54.5% of the 55 individuals had CDD, whereas 45.5% had ASD. Using an ELISA kit, the levels of serum fetuin-A were determined spectrophotometrically. The serum fetuin-A levels in the patients from the test group were found to be significantly lower than in the healthy individuals (p < 0.001). The cutoff value for the serum fetuin-A levels for cognitive developmental delay and autism spectrum disorder was 518 µg/liter, according to the results of ROC analysis (84.6% sensitivity and 91.4% specificity, AUC: 0.95, p < 0.001). The findings suggest that the serum fetuin-A level may be used to diagnose autism spectrum disorder and cognitive developmental delays.

Comparison of classification algorithms for predicting autistic spectrum disorder using WEKA modeler.

BACKGROUND: In healthcare area, big data, if integrated with machine learning, enables health practitioners to predict the result of a disorder or disease more accurately. In Autistic Spectrum Disorder (ASD), it is important to screen the patients to enable them to undergo proper treatments as early as possible. However, difficulties may arise in predicting ASD occurrences accurately, mainly caused by human errors. Data mining, if embedded into health screening practice, can help to overcome the difficulties. This study attempts to evaluate the performance of six best classifiers, taken from existing works, at analysing ASD screening training dataset. RESULT: We tested Naive Bayes, Logistic Regression, KNN, J48, Random Forest, SVM, and Deep Neural Network algorithms to ASD screening dataset and compared the classifiers' based on significant parameters; sensitivity, specificity, accuracy, receiver operating characteristic, area under the curve, and runtime, in predicting ASD occurrences. We also found that most of previous studies focused on classifying health-related dataset while ignoring the missing values which may contribute to significant impacts to the classification result which in turn may impact the life of the patients. Thus, we addressed the missing values by implementing imputation method where they are replaced with the mean of the available records found in the dataset. CONCLUSION: We found that J48 produced promising results as compared to other classifiers when tested in both circumstances, with and without missing values. Our findings also suggested that SVM does not necessarily perform well for small and simple datasets. The outcome is hoped to assist health practitioners in making accurate diagnosis of ASD occurrences in patients.

Characteristics of restricted interests in girls with ASD compared to boys: a systematic review of the literature.

The existence of a female phenotype profile in autistic spectrum disorder is one of the current hypotheses to explain the diagnostic discrepancy between men and women. In this context, an international literature review was carried out to evidence and describe the characteristics of restricted interests found in girls with autistic spectrum disorder. A documentary search was conducted on PubMed and a systematic literature review was carried out based on the PRISMA methodology. We selected studies with a population of boys and girls diagnosed as autistic according to the DSM-IV or the DSM-5, in which quantitative and descriptive comparisons of restricted interests, according to gender were carried out. Nineteen studies were found to be relevant. Fifteen enabled a refining of the characteristics of restricted interests among females: fewer restricted interests were identified in comparison with boys, and the autistic girls' interests seem to be closer to those of neurotypical girls than to those of autistic boys, which thus led to more complex screening. Age and Intelligence quotient seem to be two factors that trigger variations in restricted interests differently according to gender. Representations among professionals also have an impact on diagnoses among girls. For future research, one of the perspectives could be a comparison between girls with autism and neurotypical girls to limit gender bias. The present results contribute to potentially extending knowledge of a female phenotypical profile in autism and show the need to improve the general population's awareness, to improve health professionals' training and possibly to revise the diagnostic tools.

Simultaneous Antagonism at H3R/D2R/D3R Reduces Autism-like Self-Grooming and Aggressive Behaviors by Mitigating MAPK Activation in Mice.

Dysregulation in brain neurotransmitters underlies several neuropsychiatric disorders, e.g., autism spectrum disorder (ASD). Also, abnormalities in the extracellular-signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway pave the way for neuroinflammation, neurodegeneration, and altered learning phenotype in ASD. Therefore, the effects of chronic systemic administration of the multiple-targeting antagonist ST-713 at the histamine H3 receptor (H3R) and dopamine D2/D3 receptors (D2/D3R) on repetitive self-grooming, aggressive behaviors, and abnormalities in the MAPK pathway in BTBR T + Itpr3tf/J (BTBR) mice were assessed. The results showed that ST-713 (2.5, 5, and 10 mg/kg, i.p.) mitigated repetitive self-grooming and aggression in BTBR mice (all p < 0.05), and the ameliorative effects of the most promising dose of ST-713 (5 mg/kg, i.p.) on behaviors were completely abrogated by co-administration of the H3R agonist (R)-α-methylhistamine or the anticholinergic drug scopolamine. Moreover, the elevated levels of several MAPK pathway proteins and induced proinflammatory markers such as tumor necrosis factor (TNF-α), interleukin-1ß (IL-1ß), and IL-6 were significantly suppressed following chronic administration of ST-713 (5 mg/kg, i.p.) (all p < 0.01). Furthermore, ST-713 significantly increased the levels of histamine and dopamine in hippocampal tissue of treated BTBR mice (all p < 0.01). The current observations signify the potential role of such multiple-targeting compounds, e.g., ST-713, in multifactorial neurodevelopmental disorders such as ASD.

The Structured Preschool Participation Observation (SPO) for Children with ASD: Adaptation, Initial Psychometric Properties, and Children's Participation.

Aims: Due to the lack of tools evaluating participation of children with ASD in the educational setting, this study aimed to adapt the Structured Preschool Participation Observation (SPO), which assess the participation of preschool children attending mainstream-educational settings to children with ASD attending non-inclusive special education (content validity), to measure its initial psychometric properties (internal reliability, inter-rater reliability), and to describe children's participation characteristics, creating an effective tool to fill this gap.Methods: Content validity was evaluated by 21 experts using questionnaires. Thirty-five children with ASD were observed in their educational setting using the adapted tool (SPO-ASD).Results: Content validity was satisfactory regarding the items and their classification into occupational areas. Moderate to excellent internal consistency (α = .73-.92) and inter-rater reliability (ICC = .61-.95, p<.05) were found for all scales and most areas. Children's participation frequency was high in learning and activities of daily living (ADL), low in play and social participation. Performance level was low in social participation. Enjoyment level was low, and needed assistance in ADL was high.Conclusions: Based on our initial evaluation, the SPO-ASD may be suitable for assessing participation of children with ASD attending special education preschools. Additional studies are needed to more securely establish its psychometric properties.

A feasibility study on social competence intervention for Chinese adolescents and adults with comorbid autism spectrum disorder and intellectual disability.

BACKGROUND: Social competence training for individuals with comorbid autistic spectrum disorder (ASD) and intellectual disability was scarce and had methodological limitations in sample sizes and outcome measures. AIMS: The current study addressed the limitations and reported a social competence intervention for adolescents and adults with ASD and intellectual disability in Hong Kong, the CBT-CSCA (Mild Intellectual Disability). MATERIALS & METHODS: Thirty-three participants (aged 14-44 years, with an FSIQ 55-70) completed the 15-session intervention in a community centre. A pre-post intervention design was employed. Outcome measures included proxy-ratings on participants' social competence, autistic symptoms and behavioural problem, and participants' weekly self-evaluation on knowledge acquisition and confidence in applying skills. RESULTS: Significant improvements were shown in proxy-reported negative social behaviours, autistic symptoms and overall behavioural problems. Participants also reported satisfactory knowledge gain and confidence in applying content learnt after each session. DISCUSSION: The CBT-CSCA (Mild Intellectual Disability) is based on an established model and validated studies on ASD population. It demonstrated its applicability and emerging effectiveness in individuals with ASD and mild intellectual disability. CONCLUSION: The study supports that social competence training remains a centrality intervention approach for individuals with ASD and intellectual disability.

Perception of native and non-native phonemic contrasts in children with autistic spectrum disorder: effects of speaker variability.

The current study investigated speech perception in children with ASD by directly comparing discrimination accuracy of phonemic contrasts in the native and non-native languages. The effect of speaker variability on phoneme perception was also examined. We also explored the relation between language impairment and accuracy in phoneme discrimination in children with ASD. Significant differences in performance were found between the ASD and TD groups on discrimination of the native phonemic contrasts. By contrast, no difference was found between the two groups on discrimination of the non-native phonemic contrasts. Further subgroup analysis revealed that the ALN group (ASD without language delay or impairment) showed significantly higher discrimination accuracy for the native syllable contrasts than the non-native counterpart. No significant difference was found in the discrimination accuracy between the native and non-native phonemic contrasts in the ALD group (ASD with language delay or impairment). The effect of speaker viability on phoneme discrimination was observed in the TD group but not in the ASD subgroups. Nonverbal reasoning ability was highly related to discrimination accuracy of both the native and non-native phonemic contrasts in children with ASD. The results of the present study suggest that speech perception in children with ASD is not as attuned to their native language as in their TD peers. Our findings also indicate that language delay or impairment is related to difficulty in perception of native phonemes in children with ASD.

Presynaptic GABAB receptor-mediated network excitation in the medial prefrontal cortex of Tsc2+/- mice.

The TSC1 and TSC2 tumor suppressor genes control the activity of mechanistic target of rapamycin (mTOR) pathway. Elevated activity of this pathway in Tsc2+/- mouse model leads to reduction of postsynaptic GABAB receptor-mediated inhibition and hyperexcitability in the medial prefrontal cortex (mPFC). In this study, we asked whether presynaptic GABAB receptors (GABABRs) can compensate this shift of hyperexcitability. Experiments were performed in brain slices from adolescent wild-type (WT) and Tsc2+/- mice. Miniature and spontaneous postsynaptic currents (m/sPSCs) were recorded from layer 2/3 pyramidal neurons in mPFC using patch-clamp technique using a Cs+-based intrapipette solution. Presynaptic GABABRs were activated by baclofen (10 µM) or blocked by CGP55845 (1 µM). Independent on genotype, GABABR modulators bidirectionally change miniature excitatory postsynaptic current (mEPSC) frequency by about 10%, indicating presynaptic GABABR-mediated effects on glutamatergic transmission are comparable in both genotypes. In contrast, frequencies of both mIPSCs and sIPCSs were suppressed by baclofen stronger in Tsc2+/- neurons than in WT ones, whereas CGP55845 significantly increased (m/s)IPSC frequencies only in WT cells. Effects of baclofen and CGP55845 on the amplitudes of evoked (e)IPSCs confirmed these observations. These data indicate (1) that GABAergic synapses are inhibited by ambient GABA in WT but not in Tsc2+/- slices, and (2) that baclofen shifts the E/I ratio, determined as the ratio of (m/s)EPSC frequency to (m/s)IPSC frequency, towards excitation only in Tsc2+/- cells. This excitatory presynaptic GABABR-mediated action has to be taken into account for a possible medication of mental disorders using baclofen.

Modelling and treating GRIN2A developmental and epileptic encephalopathy in mice.

NMDA receptors play crucial roles in excitatory synaptic transmission. Rare variants in GRIN2A encoding the GluN2A subunit are associated with a spectrum of disorders, ranging from mild speech and language delay to intractable neurodevelopmental disorders, including but not limited to developmental and epileptic encephalopathy. A de novo missense variant, p.Ser644Gly, was identified in a child with this disorder, and Grin2a knock-in mice were generated to model and extend understanding of this intractable childhood disease. Homozygous and heterozygous mutant mice exhibited altered hippocampal morphology at 2 weeks of age, and all homozygotes exhibited lethal tonic-clonic seizures by mid-third week. Heterozygous adults displayed susceptibility to induced generalized seizures, hyperactivity, repetitive and reduced anxiety behaviours, plus several unexpected features, including significant resistance to electrically-induced limbic seizures and to pentylenetetrazole induced tonic-clonic seizures. Multielectrode recordings of neuronal networks revealed hyperexcitability and altered bursting and synchronicity. In heterologous cells, mutant receptors had enhanced NMDA receptor agonist potency and slow deactivation following rapid removal of glutamate, as occurs at synapses. NMDA receptor-mediated synaptic currents in heterozygous hippocampal slices also showed a prolonged deactivation time course. Standard anti-epileptic drug monotherapy was ineffective in the patient. Introduction of NMDA receptor antagonists was correlated with a decrease in seizure burden. Chronic treatment of homozygous mouse pups with NMDA receptor antagonists significantly delayed the onset of lethal seizures but did not prevent them. These studies illustrate the power of using multiple experimental modalities to model and test therapies for severe neurodevelopmental disorders, while revealing significant biological complexities associated with GRIN2A developmental and epileptic encephalopathy.

Haploinsufficiency of Tsc2 Leads to Hyperexcitability of Medial Prefrontal Cortex via Weakening of Tonic GABAB Receptor-mediated Inhibition.

Loss-of-function mutation in one of the tumor suppressor genes TSC1 or TSC2 is associated with several neurological and psychiatric diseases, including autism spectrum disorders (ASDs). As an imbalance between excitatory and inhibitory neurotransmission, E/I ratio is believed to contribute to the development of these disorders, we investigated synaptic transmission during the first postnatal month using the Tsc2+/- mouse model. Electrophysiological recordings were performed in acute brain slices of medial prefrontal cortex. E/I ratio at postnatal day (P) 15-19 is increased in Tsc2+/- mice as compared with wildtype (WT). At P25-30, facilitated GABAergic transmission reduces E/I ratio to the WT level, but weakening of tonic GABAB receptor (GABABR)-mediated inhibition in Tsc2+/- mice leads to hyperexcitability both at single cell and neuronal network level. Short (1 h) preincubation of P25-30 Tsc2+/- slices with baclofen restores the GABABR-mediated inhibition and reduces network excitability. Interestingly, the same treatment at P15-19 leads to weakening of GABABR-mediated inhibition. We hypothesize that a dysfunction of tonic GABABR-mediated inhibition might contribute to the development of ASD symptoms and suggest that GABABR activation within an appropriate time window may be considered as a therapeutic target in ASD.

A concept mobility device with multi-positional configurations and child-kind restraint for safe perioperative transfer and induction of anaesthesia in children with autistic spectrum disorder - a cross sectional study.

BACKGROUND: Transfer into the operating room, onto the operating table and mask induction of anaesthesia are major challenges faced by children with Autistic Spectrum Disorder (ASD). In a pilot study, parents observed that perioperative transfer becomes unsafe and difficult when children with ASD becomes uncooperative. METHOD: A CHILD-KIND CONCEPT mobility system comprising of multi-positioning seat configurations and restraining module was developed with inputs from multi-disciplinary healthcare professionals and parents with children with ASD. To appeal to children and motivate child-machine interaction, the seat configurations and restraining module are designed to take the form of child-friendly, non-threatening, fun and familiar items. The sitting configuration, sitting to supine transformation, the restraint modules resemble racing-car seat, reclining motion of a home massage chair, safety restraints found in airplanes and amusement rides respectively. Healthcare professionals (HCPs) involved in the perioperative patient care, parents of ASD children and children (neurotypical and ASD) experience the use of the system in a non-clinical environment and participated in a survey study. The acceptance of its functionality (HCPs, parents) for perioperative transfer and induction of anaesthesia, rating of the user experience and likes and dislikes of (parents and children) were obtained. RESULTS: Thirty-two HCPs, 30 parents and 23 children participated. Majority of parents and HCPs opined the use of the system enables improvement in the management of perioperative movement (90.0% parents, 100% HCPs), safe perioperative movement (86.7% parents, 96.9% HCPs) and promotes ease of anaesthesia induction (76.7% parents, 90.6% HCPs) for uncooperative combative ASD children. Overall, 93.8% HCPs and 86.7% parents would recommend its frequent use in their own practice and their ASD children respectively. Attractiveness and multi-functionality are attributes endorsed by parents and children. Children endorse its use for induction of anaesthesia (73.9%), dental chair (82.6%), intra-hospital transfer (95.7%). CONCLUSION: A child-kind mobility device that integrates appeal with functionality of restraint and multi-positional transformation has a potential to promote safe perioperative movement and ease of induction of anaesthesia in anxious uncooperative ASD children.