1. Bódi V, Májer T, Kelemen V, Világi I, Szűcs A, Varró P. Alterations of the Hippocampal Networks in Valproic Acid-Induced Rat Autism Model. Frontiers in neural circuits. 2022; 16: 772792.

Autism Spectrum Disorder (ASD) is one of the most frequently diagnosed neurodevelopmental disorders, characterized among others by impairments in social interactions and repetitive behavior. According to one of the leading hypotheses about its origin, ASD is caused by the imbalance of excitatory and inhibitory circuit activity. ASD-related morphological and functional changes can be observed in several brain regions i.e., in the prefrontal cortex and the hippocampus. It is well-established that prenatal valproic-acid (VPA) exposure of rats on day 12.5 leads to neurodevelopmental alterations with autism-like clinical and behavioral symptoms. The aim of this study was to investigate potential changes in the excitability of neuronal networks and individual neurons of the hippocampus elicited by prenatal VPA treatment. As there are marked sex differences in ASD, offspring of both sexes were systematically tested, using two different age groups, to elucidate eventual differences in neurodevelopment after VPA treatment. Excitatory connections and long-term synaptic plasticity as well as intrinsic excitability of CA1 pyramidal cells were examined. Pregnant female Wistar rats received saline or 500 mg/kg VPA i. p. on gestation day 12.5. Brain slices of 6-week-old and 3-month-old offspring were investigated using extra- and intracellular electrophysiological techniques. Field potential- and whole-cell patch clamp recordings were carried out to measure network excitability and single cell activity in the CA1 region hippocampus. Enhanced excitability of hippocampal networks was detected in the 6-week-old VPA-treated male rats; however, this change could not be observed in 3-month-old males. Intrinsic excitability of single neurons, however, was increased in 3-month-old males. In 6-week-old treated females, the most prominent effect of VPA was an increase in voltage sag, to a similar degree to the neurons of the older age group. In 3-month-old females, a network excitability increase could be demonstrated, in a lesser degree than in younger males. It can be concluded, that VPA treatment had diverse effects on hippocampal excitability depending on the sex and the age of the animals. We found that certain alterations manifested in 6-week-old rats were compensated later, on the other hand, other changes persisted until the age of 3 months.

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2. Caldani S, Humeau E, Delorme R, Bucci MP. Dysfunction in inhibition and executive capabilities in children with autism spectrum disorder: An eye tracker study on memory guided saccades. Applied neuropsychology Child. 2022: 1-6.

BACKGROUND: Dysmetria in children with autism spectrum disorders is considered depend on executive dysfunctions. To explore the impact of inhibitory control and working memory on oculomotor performance in children with autism spectrum disorder (ASD), we used the memory guided saccade (MGS) paradigm. METHOD: We enrolled in our study a group of 26 children with ASD and in a group of 26 children age-, sex-, and IQ-matched of with typically development, using only one single delay period and one single stimulus amplitude. We recorded with a video eye-tracker system- the latency and the accuracy of the MGS as well as the number of anticipatory saccades during the MGS paradigm. RESULTS: Children with ASD displayed significant increased latency (p < .01), decreased amplitude of memory guided saccades (p < .01) and an elevated number of anticipatory saccades (p < .003), when compared to age-, sex-, IQ- matched children with typical development. CONCLUSION: These abnormalities may underline the executive dysfunctions frequently reported in ASD: the increased latency and the decreased amplitude of memory guides saccades may be related to planning and working memory impairments; the increased number of anticipatory saccades may be linked to a deficit in inhibitory control.

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3. Cebreros-Paniagua R, Ayala-Guerrero F, Mateos-Salgado EL, Villamar-Flores CI, Gutiérrez-Chávez CA, Jiménez-Correa U. Analysis of sleep spindles in children with Asperger’s syndrome. Sleep science (Sao Paulo, Brazil). 2021; 14(3): 201-6.

Sleep spindles are an element of the sleep microstructure observed on the EEG during the NREM sleep phase. Sleep spindles are associated to sleep stability functions as well as memory consolidation and optimization of different cognitive processes. On the other hand, Asperger’s syndrome (AS) is a generalized developmental disorder in which cognitive and sleep disturbances have been described. In this study we analyzed different characteristics of sleep spindles in a group of children with AS and compared them with sleep spindles of a group of children with typical development paired by age; both groups ranged from 6 to 12 years of age and were all male. We observed a statistically significant decrease in sleep spindles intrinsic frequency in different brain regions in the AS group in relation to the typical development group. This finding could be due to immaturity in brain regions related to the integration of sleep spindles; and this immaturity could be related with cognitive aspects in these patients.

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4. Chen Y, Liu A, Fu X, Wen J, Chen X. An Invertible Dynamic Graph Convolutional Network for Multi-Center ASD Classification. Frontiers in neuroscience. 2021; 15: 828512.

Autism Spectrum Disorder (ASD) is one common developmental disorder with great variations in symptoms and severity, making the diagnosis of ASD a challenging task. Existing deep learning models using brain connectivity features to classify ASD still suffer from degraded performance for multi-center data due to limited feature representation ability and insufficient interpretability. Given that Graph Convolutional Network (GCN) has demonstrated superiority in learning discriminative representations of brain connectivity networks, in this paper, we propose an invertible dynamic GCN model to identify ASD and investigate the alterations of connectivity patterns associated with the disease. In order to select explainable features from the model, invertible blocks are introduced in the whole network, and we are able to reconstruct the input dynamic features from the network’s output. A pre-screening of connectivity features is adopted to reduce the redundancy of the input information, and a fully-connected layer is added to perform classification. The experimental results on 867 subjects show that our proposed method achieves superior disease classification performance. It provides an interpretable deep learning model for brain connectivity analysis and is of great potential in studying brain-related disorders.

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5. Clairmont C, Wang J, Tariq S, Sherman HT, Zhao M, Kong XJ. The Value of Brain Imaging and Electrophysiological Testing for Early Screening of Autism Spectrum Disorder: A Systematic Review. Frontiers in neuroscience. 2021; 15: 812946.

Given the significance of validating reliable tests for the early detection of autism spectrum disorder (ASD), this systematic review aims to summarize available evidence of neuroimaging and neurophysiological changes in high-risk infants to improve ASD early diagnosis. We included peer-reviewed, primary research in English published before May 21, 2021, involving the use of magnetic resonance imaging (MRI), electroencephalogram (EEG), or functional near-infrared spectroscopy (fNIRS) in children with high risk for ASD under 24 months of age. The main exclusion criteria includes diagnosis of a genetic disorder and gestation age of less the 36 weeks. Online research was performed on PubMed, Web of Science, PsycINFO, and CINAHL. Article selection was conducted by two reviewers to minimize bias. This research was funded by Massachusetts General Hospital Sundry funding. IRB approval was not submitted as it was deemed unnecessary. We included 75 primary research articles. Studies showed that high-risk infants had divergent developmental trajectories for fractional anisotropy and regional brain volumes, increased CSF volume, and global connectivity abnormalities on MRI, decreased sensitivity for familiar faces, atypical lateralization during facial and auditory processing, and different spectral powers across multiple band frequencies on EEG, and distinct developmental trajectories in functional connectivity and regional oxyhemoglobin concentrations in fNIRS. These findings in infants were found to be correlated with the core ASD symptoms and diagnosis at toddler age. Despite the lack of quantitative analysis of the research database, neuroimaging and electrophysiological biomarkers have promising value for the screening of ASD as early as infancy with high accuracy, which warrants further investigation.

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6. Fletcher-Watson S. Transdiagnostic research and the neurodiversity paradigm: commentary on the transdiagnostic revolution in neurodevelopmental disorders by Astle et al. Journal of child psychology and psychiatry, and allied disciplines. 2022; 63(4): 418-20.

In their comprehensive and articulate paper on the Transdiagnostic Revolution in Neurodevelopmental Disorders, Astle, Holmes, Kievit and Gathercole (2021) ‘consider how well current classifications of neurodevelopmental disorders serve our understanding’. They examine the lack of mapping between clinical diagnoses such as ADHD or autism and research data at other levels of explanation, including genetics, neural structure and function, and cognition. The authors come to the conclusion that, if our goal is to explain variability and complexity, understand mechanisms and guide support decisions, ‘diagnostic taxonomies that classify individuals in terms of discrete categories are ill-suited’. In this commentary, I explore alignment between their account of the transdiagnostic revolution and the neurodiversity paradigm and identify how transdiagnostic methods may promote neurodiversity-affirmative research and practice.

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7. Gamarra Choque PM, Rivera Arellano EG, Reynosa Navarro E, Méndez Vergaray J, Huayta-Franco YJ, Muñante Toledo MF. Children with severe disabilities: adaptation, virtual education, and prospects. Experiences of three Peruvian mothers, COVID-19 context. Journal of medicine and life. 2022; 15(1): 43-51.

This study aimed to reveal and investigate mothers’ experiences of students with severe disabilities regarding learning in distance education in Lima-Peru. This is a phenomenological study focused on understanding the world of mothers regarding the education of their children with severe disabilities. Their discourse focused on four categories: being the mother of a child with severe disability, pandemic category, virtual education, and family prospects. The participants were three mothers of children with Down Syndrome, Autism Spectrum Disorder, and Cerebral Palsy. An in-depth interview structured in 26 questions was used, applied face to face. With distance education, the mothers consider that their children’s abilities and skills have assumed a leading role, developed creativity, and employed various strategies to comply with school activities. In addition, it also strengthened their family ties despite the pandemic.

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8. Gupta M, Gupta N, Moll J. Duration of untreated autism in rural America: emerging public health crisis. CNS spectrums. 2022: 1-4.

The rural areas have been at the receiving end amidst mental health disparity across the USA. There is a serious and concerning divide among ones with autism spectrum disorders (ASDs) living in underserved areas as compared to urban residents. With the higher than ever prevalence of ASD as per the recent reports of the Centers for Disease Control and Prevention; there is a need for a closer look at the prevailing issues. The trends are reflecting marked underdiagnosis, late diagnosis, lack of evidence-based diagnostic measures and interventions. These factors interplay in worsening the mental health crisis and there is an urgent need for corrective measures to address these highly modifiable problems.

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9. Iversen S, Kildahl AN. Case Report: Mechanisms in Misdiagnosis of Autism as Borderline Personality Disorder. Frontiers in psychology. 2022; 13: 735205.

Autistic individuals without intellectual disabilities are sometimes not diagnosed until adolescence/adulthood. Due to increased risk of co-occurring mental health problems, these individuals may initially be referred to general, mental health services and not always be identified as autistic; some may be misdiagnosed with personality disorder (PD) prior to identification of autism. To explore possible mechanisms in misdiagnosis of autism, we report on the case of a young man with severe, non-suicidal self-injury (NSSI) and attention deficit disorder (ADD) who had been diagnosed with and treated for borderline PD prior to being diagnosed with autism. Following reassessment by mental health clinicians with experience of working with autistic individuals, the patient was diagnosed with autism, ADD, and depression-but not PD. Experiences from this case suggest that presence of co-occurring NSSI, depression, and ADD, as well as lack of comprehensive assessment and lack of autism knowledge in general mental health services, may contribute to risk that autism is misdiagnosed as PD. These findings highlight the need for autism expertise in general mental health services to facilitate appropriate diagnosis for autistic individuals who encounter these services, as well as the importance of undertaking comprehensive assessments.

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10. Iwabuchi T, Takahashi N, Nishimura T, Rahman MS, Harada T, Okumura A, Kuwabara H, Takagai S, Nomura Y, Matsuzaki H, Ozaki N, Tsuchiya KJ. Associations Among Maternal Metabolic Conditions, Cord Serum Leptin Levels, and Autistic Symptoms in Children. Frontiers in psychiatry. 2021; 12: 816196.

INTRODUCTION: Accumulating evidence has shown that maternal metabolic conditions, such as pre-pregnancy overweight, diabetes mellitus, and hypertensive disorders of pregnancy (HDP) are potential risk factors of autism spectrum disorder (ASD). However, it remains unclear how these maternal conditions lead to neurodevelopmental outcomes in the offspring, including autistic symptoms. Leptin, an adipokine that has pro-inflammatory effects and affects fetal neurodevelopment, is a candidate mediator of the association between maternal metabolic factors and an increased risk of ASD. However, whether prenatal exposure to leptin mediates the association between maternal metabolic conditions and autistic symptoms in children has not been investigated yet. METHODS: This study investigated the associations between mothers’ metabolic conditions (pre-pregnancy overweight, diabetes mellitus during or before pregnancy, and HDP), leptin concentrations in umbilical cord serum, and autistic symptoms among 762 children from an ongoing cohort study, using generalized structural equation modeling. We used the Social Responsive Scale, Second Edition (SRS-2) at 8-9 years old to calculate total T-scores. Additionally, we used the T-scores for two subdomains: Social Communication and Interaction (SCI) and Restricted Interests and Repetitive Behavior (RRB). RESULTS: Umbilical cord leptin levels were associated with pre-pregnancy overweight [coefficient = 1.297, 95% confidence interval (CI) 1.081-1.556, p = 0.005] and diabetes mellitus (coefficient = 1.574, 95% CI 1.206-2.055, p = 0.001). Furthermore, leptin levels were significantly associated with SRS-2 total T-scores (coefficient = 1.002, 95% CI 1.000-1.004, p = 0.023), SCI scores (coefficient = 1.002, 95% CI 1.000-1.004, p = 0.020), and RRB scores (coefficient = 1.001, 95% CI 1.000-1.003, p = 0.044) in children. Associations between maternal metabolic factors and autistic symptoms were not significant. DISCUSSION: The present study uncovered an association between cord leptin levels and autistic symptoms in children, while maternal metabolic conditions did not have an evident direct influence on the outcome. These results imply that prenatal pro-inflammatory environments affected by maternal metabolic conditions may contribute to the development of autistic symptoms in children. The findings warrant further investigation into the role of leptin in the development of autistic symptoms.

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11. Kotajima-Murakami H, Hagihara H, Sato A, Hagino Y, Tanaka M, Katoh Y, Nishito Y, Takamatsu Y, Uchino S, Miyakawa T, Ikeda K. Exposure to GABA(A) Receptor Antagonist Picrotoxin in Pregnant Mice Causes Autism-Like Behaviors and Aberrant Gene Expression in Offspring. Frontiers in psychiatry. 2022; 13: 821354.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is characterized by impairments in social interaction and restricted/repetitive behaviors. The neurotransmitter γ-aminobutyric acid (GABA) through GABA(A) receptor signaling in the immature brain plays a key role in the development of neuronal circuits. Excitatory/inhibitory imbalance in the mature brain has been investigated as a pathophysiological mechanism of ASD. However, whether and how disturbances of GABA signaling in embryos that are caused by GABA(A) receptor inhibitors cause ASD-like pathophysiology are poorly understood. The present study examined whether exposure to the GABA(A) receptor antagonist picrotoxin causes ASD-like pathophysiology in offspring by conducting behavioral tests from the juvenile period to adulthood and performing gene expression analyses in mature mouse brains. Here, we found that male mice that were prenatally exposed to picrotoxin exhibited a reduction of active interaction time in the social interaction test in both adolescence and adulthood. The gene expression analyses showed that picrotoxin-exposed male mice exhibited a significant increase in the gene expression of odorant receptors. Weighted gene co-expression network analysis showed a strong correlation between social interaction and enrichment of the « odorant binding » pathway gene module. Our findings suggest that exposure to a GABA(A) receptor inhibitor during the embryonic period induces ASD-like behavior, and impairments in odorant function may contribute to social deficits in offspring.

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12. Mandic-Maravic V, Grujicic R, Milutinovic L, Munjiza-Jovanovic A, Pejovic-Milovancevic M. Dopamine in Autism Spectrum Disorders-Focus on D2/D3 Partial Agonists and Their Possible Use in Treatment. Frontiers in psychiatry. 2021; 12: 787097.

Autism spectrum disorders (ASD) are a group of disorders characterized by impairment in social communication and repetitive and stereotyped behaviors. ASD etiology is very complex, including the effect of both genetic and environmental factors. So far, no specific treatment for the core symptoms of ASD has been developed, although attempts have been made for the treatment of repetitive behavior. The pharmacological treatment is aimed at treating non-specific symptoms such as irritability and aggression. Recent studies pointed out to the possible role of altered dopamine signaling in mesocorticolimbic and nigrostriatal circuits in ASD. In addition, several research pointed out to the association of dopamine receptors polymorphism and ASD, specifically repetitive and stereotyped behavior. In this paper, we will provide a review of the studies regarding dopamine signaling in ASD, existing data on the effects of D2/D3 partial agonists in ASD, possible implications regarding their individual receptor profiles, and future perspectives of their possible use in ASD treatment.

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13. Masoudi M, Maasoumi R, Effatpanah M, Bragazzi NL, Montazeri A. Exploring experiences of psychological distress among Iranian parents in dealing with the sexual behaviors of their children with autism spectrum disorder: a qualitative study. Journal of medicine and life. 2022; 15(1): 26-33.

Sexual behavior is influenced by social and communication deficits in autism spectrum disorder (ASD) and is a serious challenge for parents who lack effective strategies for providing sexual education to their children with ASD. The purpose of this study was to explore Iranian parents’ experiences of psychological distress in dealing with the sexual behaviors of their children with ASD. This qualitative study was designed following the conventional content analysis approach. Semi-structured and in-depth interviews were conducted with 27 parents of children with ASD aged 8-34 years. All interviews were audio-recorded and transcribed verbatim. The data were collected through purposeful sampling and continued until data saturation. The worries theme was extracted from data interpretation using qualitative content analysis, and this theme entailed four subthemes: 1) sexual vulnerability, 2) unintended social consequences, 3) psychological suffering, and 4) confusion about the future of a child’s sex life. This study emphasized the importance of paying attention to parents’ concerns about the sexual behaviors of children with ASD. Parents’ psychological distress is a major obstacle to proper coping with sexual behaviors, and using coping strategies may help reduce psychological distress in parents of children with ASD. Therefore, it is necessary to design, implement, and evaluate culture-appropriate educational programs to address parents’ concerns regarding the sexual health of a child with autism.

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14. Naeem AA, El-Boraie HA, Abou-Elsaad TA, Khater ME, Manzar MD, Spence DW, Pandi-Perumal SR, Zaki NF. Can sleep profiles predict autistic traits in siblings of children with autism spectrum disorder?. Sleep science (Sao Paulo, Brazil). 2021; 14(3): 214-23.

INTRODUCTION: As the prevalence of ASD (autism spectrum disorder) continues to rise, so does the need to evaluate the impact of associated difficulties on both the diagnosed child and the immediate family. OBJECTIVES: The aim of the present study was to assess reports of sleep disturbance or abnormal sleep behaviours (sleep profiles) in the siblings of diagnosed autistic children (referred to throughout this study as high-risk siblings, or HR-sibs) and to determine if these sleep patterns correlated with evidence of disturbed sleep among their siblings who had full symptoms of autistic spectrum disorder. MATERIAL AND METHODS: This case control cross-sectional study investigated 64 autistic children, 80 HR-sibs, and 80 typically developing children. Each study subject was assessed for sleep problems and autistic traits through the use of a sleep-wake diary, a school sleep habit survey, and a childhood autism spectrum test. RESULTS: Children with autism spectrum disorders and their HR-sibs showed no significant differences regarding their sleep profiles. Typically, developing children had more middle insomnia than HR-sibs and had more wake latency. CONCLUSION: Increased risks for sleep problems in children with autism and their HR-sibs emphasized the importance of early screening for sleep problems in children with autism and their siblings.

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15. Puricelli C, Rolla R, Gigliotti L, Boggio E, Beltrami E, Dianzani U, Keller R. The Gut-Brain-Immune Axis in Autism Spectrum Disorders: A State-of-Art Report. Frontiers in psychiatry. 2021; 12: 755171.

The interest elicited by the large microbial population colonizing the human gut has ancient origins and has gone through a long evolution during history. However, it is only in the last decades that the introduction of high-throughput technologies has allowed to broaden this research field and to disentangle the numerous implications that gut microbiota has in health and disease. This comprehensive ecosystem, constituted mainly by bacteria but also by fungi, parasites, and viruses, is proven to be involved in several physiological and pathological processes that transcend the intestinal homeostasis and are deeply intertwined with apparently unrelated body systems, such as the immune and the nervous ones. In this regard, a novel speculation is the relationship between the intestinal microbial flora and the pathogenesis of some neurological and neurodevelopmental disorders, including the clinical entities defined under the umbrella term of autism spectrum disorders. The bidirectional interplay has led researchers to coin the term gut-brain-immune system axis, subverting the theory of the brain as an immune-privileged site and underscoring the importance of this reciprocal influence already from fetal life and especially during the pre- and post-natal neurodevelopmental process. This revolutionary theory has also unveiled the possibility to modify the gut microbiota as a way to treat and even to prevent different kinds of pathologies. In this sense, some attempts have been made, ranging from probiotic administration to fecal microbiota transplantation, with promising results that need further elaboration. This state-of-art report will describe the main aspects regarding the human gut microbiome and its specific role in the pathogenesis of autism and its related disorders, with a final discussion on the therapeutic and preventive strategies aiming at creating a healthy intestinal microbial environment, as well as their safety and ethical implications.

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16. Rowland ME, Jajarmi JM, Osborne TSM, Ciernia AV. Insights Into the Emerging Role of Baf53b in Autism Spectrum Disorder. Frontiers in molecular neuroscience. 2022; 15: 805158.

Accurate and precise regulation of gene expression is necessary to ensure proper brain development and plasticity across the lifespan. As an ATP-dependent chromatin-remodeling complex, the BAF (Brg1 Associated Factor) complex can alter histone-DNA interactions, facilitating dynamic changes in gene expression by controlling DNA accessibility to the transcriptional machinery. Mutations in 12 of the potential 29 subunit genes that compose the BAF nucleosome remodeling complex have been identified in several developmental disorders including Autism spectrum disorders (ASD) and intellectual disability. A novel, neuronal version of BAF (nBAF) has emerged as promising candidate in the development of ASD as its expression is tied to neuron differentiation and it’s hypothesized to coordinate expression of synaptic genes across brain development. Recently, mutations in BAF53B, one of the neuron specific subunits of the nBAF complex, have been identified in patients with ASD and Developmental and epileptic encephalopathy-76 (DEE76), indicating BAF53B is essential for proper brain development. Recent work in cultured neurons derived from patients with BAF53B mutations suggests links between loss of nBAF function and neuronal dendritic spine formation. Deletion of one or both copies of mouse Baf53b disrupts dendritic spine development, alters actin dynamics and results in fewer synapses in vitro. In the mouse, heterozygous loss of Baf53b severely impacts synaptic plasticity and long-term memory that is reversible with reintroduction of Baf53b or manipulations of the synaptic plasticity machinery. Furthermore, surviving Baf53b-null mice display ASD-related behaviors, including social impairments and repetitive behaviors. This review summarizes the emerging evidence linking deleterious variants of BAF53B identified in human neurodevelopmental disorders to abnormal transcriptional regulation that produces aberrant synapse development and behavior.

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17. Xavier SD. The relationship between autism spectrum disorder and sleep. Sleep science (Sao Paulo, Brazil). 2021; 14(3): 193-5.

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